2024 POSTER ABSTRACTS
(sorted alphabetically by title)
26A Young Heart Under Pressure: Unraveling Cardiometabolic Syndrome
Michelle Nabi MD, Ryanne Burke NP, Kevin O’Day MD
- Department of Medicine, 2. Division of Cardiovascular Medicine, UMass Chan Medical School, Worcester, MA, USA
Purpose: Cardiometabolic syndrome (CMS) is due to a complex interplay of genetic factors, sedentary behavior, poor diet, and hormonal imbalances, leading to obesity and insulin resistance. The clinical impact of CMS extends beyond cardiovascular disease and diabetes, encompassing conditions like metabolic dysfunction-associated steatotic liver disease, cancer, and sleep apnea. Restoring metabolic balance through lifestyle changes, such as an improved diet and regular physical activity, is crucial in management.
Methods: We report a case of a young male with a BMI of 36 kg/m² with no known past medical history who was found to be in a hypertensive emergency with severe renal injury, dyslipidemia, and hypertensive cardiomyopathy.
Results: A 25-year-old male with a BMI of 36 and no known prior medical history presented with a 2-week history of dyspnea, orthopnea, and paroxysmal nocturnal dyspnea. His vitals were notable for a blood pressure of 173/124, heart rate of 97, and oxygen saturation above 95% on room air. Physical examination revealed trace pitting edema in the lower extremities but was otherwise unremarkable.
A chest x-ray showed patchy opacities in both lungs suggesting increased pulmonary vasculature. Lab results included an NT pro-BNP greater than 16,000 ng/L and a high sensitivity troponin of 139 ng/L. BUN and Creatinine measured 87 mg/dL and 6.46 mg/dL, respectively. Urinalysis showed 3+ protein. Lipid panel results included total
cholesterol of 252, LDL of 190, HDL of 41, and triglycerides of 107. Hemoglobin A1c was 5.2%, and thyroid-stimulating hormone was within normal limits. A C-reactive protein and erythrocyte sedimentation rate measured 76 mg/L and 56 mm/hr, respectively. An EKG showed normal sinus rhythm with lateral ST depressions and associated T-wave abnormalities. An echocardiogram revealed an ejection fraction of 27%, normal LV cavity size with a high mass index, and increased wall thickness. Changes were consistent with concentric left ventricular hypertrophy. He was initiated on pharmacotherapy for hypertension with hydralazine and carvedilol leading to improvement in his pressures. Effective diuresis was achieved with a loop diuretic. An extensive lab panel regarding his renal injury including protein electrophoresis was negative. Renal ultrasound demonstrated hyperechoic texture and cortical thinning of the bilateral kidneys. A renal biopsy revealed crescentic IgA nephropathy. He was started on prednisone.
Conclusions: This case offers an unusual presentation of cardiometabolic syndrome manifesting as hypertensive emergency, severe renal dysfunction, and hypertensive cardiomyopathy. In particular, this case highlights the importance of early intervention for younger patients. Cardiometabolic risk factors, if identified and managed early, can prevent the premature onset of serious complications such as heart failure and CKD. Although this patient had no known medical history, his imaging and bloodwork indicate the effects of chronic hypertension. Thus, even in younger patient demographics, having regular access to healthcare is crucial in preventing the consequences of cardiometabolic syndrome. Close multidisciplinary collaboration is essential to address the patient’s cardiovascular, renal, and metabolic challenges.
Disclosures: Nothing to disclose by any author.
25Analysis of Glucose Biomarkers in Phase I and Phase II Studies of Survodutide in People with Type 2 Diabetes or Living With Overweight/Obesity
Elif Ekinci, Jorge Arrubla, Anita M. Hennige, Corinna Schoelch
Australian Centre for Accelerating Diabetes Innovations, Melbourne Medical School, The University of Melbourne, Melbourne, Victoria, Australia;Department of Medicine, Austin Health, University of Melbourne, Melbourne, Victoria, Australia;Department of Endocrinology, Austin Health, Melbourne, Victoria, Australia;Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany;Boehringer Ingelheim International GmbH, Biberach, Germany;Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany
Purpose: Survodutide, a glucagon receptor/glucagon-like peptide-1 receptor (GCGR/GLP-1R) dual agonist, elicited greater HbA1c reduction up to –1.71% vs semaglutide 1 mg (–1.47%) in a Phase 2 trial in patients with type 2 diabetes. This analysis evaluated changes in insulin sensitivity, pancreatic islet cell function, and glucose biomarkers from three Phase I/II trials of survodutide.
Methods: Descriptive statistics were derived from a Phase 2 trial in patients living with obesity/overweight without diabetes (NCT04667377), a Phase 2 trial in patients with type 2 diabetes (NCT04153929), and a Phase 1 study in patients living with obesity/overweight (NCT03591718).
Results: High survodutide doses was associated with improved insulin sensitivity as reflected in a decrease in mean absolute homeostasis model assessment of insulin resistance (HOMA-IR) scores from baseline (BL) to the end of treatment, in contrast to no change or increase with placebo (PBO): NCT04667377, –1.1 (4.8 mg once weekly) vs –0.2 at Week 46;NCT04153929, –0.9 (1.8 mg twice weekly vs 0.9 at Week 17;and NCT03591718, –1.0 (2.4 mg twice weekly following up titration) vs 0.3 at Week 16.
Survodutide was associated with improved homeostasis model assessment of β-cell function (HOMA-β), with mean percentage change from BL to end of treatment consistently higher vs PBO: NCT04667377, 8.6% vs –1.1%;NCT04153929, 88.0% vs 18.0%. In NCT04667377, change from BL to Week 46 in fasting plasma glucose with survodutide vs PBO was 0.4 vs 0.0 mmol/L. Change from BL in insulin and non-fasting plasma glucose levels with survodutide 4.8 mg vs PBO, was –23.4 vs 0.4 pmol/L and –0.0 vs 0.6 mmol/L, respectively. Additionally, mean change from BL to Week 46 in adiponectin, glucagon, and c-peptide levels with survodutide 4.8 mg vs PBO was 1.9 vs –0.15 mg/L, –15.2 vs –0.8 pmol/L, and –0.1 vs 0.0 nmol/L, respectively.
Conclusions: Survodutide treatment was associated with improvement in markers of insulin sensitivity, pancreatic islet cell function, and glucose biomarkers, in patients living with obesity/overweight and those with type 2 diabetes. *This is an encore abstract
Disclosures: EIE is a consultant to Bayer and Eli Lilly, Australia and her institute reports research funding support from Amgen, Bayer, Boehringer Ingelheim, Eli Lilly Australia, and Versanis;JA, AMH, and CS are employees of Boehringer Ingelheim.
This encore abstract was originally presented at the American Diabetes Association (ADA) 84th Scientific Sessions 2024 (Orlando, FL, USA/Hybrid; Jun 21–24, 2024)
14Effect of Low Glycemic Index Diet on Anthropometric Parameters and Interleukin Levels in Patients with Metabolic Syndrome and Ischemic Heart Disease
Bakhromkhon Alyavi, Jamol Uzokov, Djamshid Payziev, Akbar Abdullaev
Republican Specialized Scientific Practical Medical Center of Therapy and Medical Rehabilitation
Purpose: The purpose of this study was to evaluate the impact of a low glycemic index (LGI) diet on anthropometric parameters and interleukin levels in patients diagnosed with metabolic syndrome and ischemic heart disease (IHD). Dyslipidemia, a critical component of metabolic syndrome, contributes significantly to cardiovascular risk. The LGI diet, known for its potential benefits in regulating blood glucose and lipid levels, was hypothesized to improve cardiometabolic health markers compared to a routine diet. This study aimed to assess whether an LGI diet could offer superior benefits in terms of weight reduction, waist circumference, and inflammatory markers, specifically interleukin-6 (IL-6) and interleukin-10 (IL-10), which are pivotal in the pathophysiology of both metabolic syndrome and IHD.
Methods: A total of 126 patients with metabolic syndrome and ischemic heart disease were enrolled in this randomized controlled trial. Participants were divided into two groups: the intervention group (n=63), which followed an LGI diet, and the control group (n=63), which followed a routine diet for 12 weeks. Anthropometric parameters, including body weight, body mass index (BMI), and waist circumference, were measured at baseline and post-intervention. Blood samples were collected to analyze lipid profiles and levels of interleukins (IL-6 and IL-10) using enzyme-linked immunosorbent assay (ELISA). Statistical analysis was performed using SPSS software, with paired t-tests and ANOVA used to assess within-group and between-group differences.
Results: The LGI diet group demonstrated significant reductions in body weight, BMI, and waist circumference compared to the control group. Mean weight loss in the LGI group was 4.2 ± 1.1 kg, while the control group showed a mean weight loss of 2.3 ± 0.9 kg (p < 0.01). BMI decreased by 1.6 ± 0.4 kg/m² in the LGI group versus 0.8 ± 0.3 kg/m² in the control group (p < 0.05). Waist circumference reduction was also more pronounced in the LGI group (5.1 ± 1.2 cm) compared to the control group (2.7 ± 1.0 cm, p < 0.01). Regarding inflammatory markers, IL-6 levels decreased significantly in the LGI diet group from 7.2 ± 1.5 pg/mL to 4.9 ± 1.3 pg/mL (p < 0.01), while the control group showed a smaller reduction from 7.4 ± 1.4 pg/mL to 6.8 ± 1.2 pg/mL (p > 0.05). Conversely, IL-10 levels increased significantly in the LGI group from 3.5 ± 0.8 pg/mL to 5.1 ± 1.1 pg/mL (p < 0.01), with the control group showing no significant change (3.4 ± 0.9 pg/mL to 3.7 ± 1.0 pg/mL, p > 0.05).
Conclusions: The findings of this study suggest that a low glycemic index diet is more effective than a routine diet in improving anthropometric parameters and modulating inflammatory markers in patients with metabolic syndrome and ischemic heart disease. The significant reductions in body weight, BMI, and waist circumference indicate better overall weight management, which is critical in reducing cardiovascular risk. Furthermore, the marked decrease in IL-6 levels and increase in IL-10 levels in the LGI diet group highlight the anti-inflammatory benefits of this dietary intervention. These results support the implementation of an LGI diet as a therapeutic strategy for patients with metabolic syndrome and IHD to enhance cardiometabolic health outcomes. Further research is warranted to explore the long-term benefits and potential mechanisms underlying the observed effects.
Disclosures: Nothing to disclose by any authors
21Effectiveness of empagliflozin in patients with heart failure and COPD: Results from EMPEROR-Preserved and EMPEROR-Reduced
Stephan von Haehling, Javed Butler, and Stefan D. Anker on behalf of the EMPEROR Executive Committee
University Medical Centre of Göttingen (UMG), Göttingen, Germany; Baylor Scott & White Research Institute, Dallas, TX, USA; Berlin Institute of Health Center for Regenerative Therapies, Berlin, Germany
Purpose: Heart failure (HF) and chronic obstructive pulmonary disease (COPD) are chronic, progressive syndromes that share numerous risk factors and clinical symptoms. We sought to analyze the relationship between COPD status and outcomes in patients receiving empagliflozin or placebo in the EMPEROR-Preserved and EMPEROR-Reduced trials.
Methods: Patients with and without COPD were compared with respect to baseline characteristics and outcomes following treatment with empagliflozin. The primary endpoint was first HF hospitalization or CV death. Additional endpoints included HF hospitalizations, cardiovascular and all-cause mortality, quality of life using the Kansas City Cardiomyopathy Questionnaire (KCCQ) and adverse events.
Results: We analyzed data of 9,718 patients, including 1,238 (12.7%) with COPD. Compared to patients without COPD, patients with COPD were more likely to be in NYHA class III (19.4 vs. 28.4%), to be male (62.4 vs. 69.0%), to have higher body mass index (29.0±5.7 vs. 29.5±6.1 kg/m2), to be white, to be smoker or ex-smoker (47.1 vs. 71.9%), to be older (69.6±10.5 vs. 72.1±8.7 years, all p<0.0001), to have a longer duration of HF (5.0 vs. 5.4 years, p=0.04), to have higher hemoglobin and high-sensitivity troponin T values (both p<0.01), and a trend towards more advanced kidney dysfunction. Patients with COPD exhibited a higher adjusted risk of reaching the primary endpoint of first HF hospitalization or CV death compared to those without COPD (adjusted hazard ratio [HR] 1.52, 95% confidence interval [95% CI] 1.28-1.80, p<0.0001). The favorable impact of empagliflozin on the primary outcome remained consistent regardless of COPD status at baseline (no COPD: HR 0.76, 95% CI 0.68-0.84, COPD: HR 0.82, 95% CI 0.66-1.03, p for interaction 0.50).
The effect on HF hospitalizations, cardiovascular and all-cause mortality was not affected by COPD status. The KCCQ showed similar improvement in patients with or without COPD treated with empagliflozin. The distribution of adverse events was comparable between patients receiving empagliflozin and those on placebo, irrespective of COPD status at baseline.
Conclusions: COPD is frequently encountered in patients with HF and associated with worse outcomes. Among patients with COPD, treatment with empagliflozin is associated with consistent efficacy on outcomes and improvement in quality of life as in patients without COPD. This is an encore submission.
Disclosures: SH has been a paid consultant for or received honoraria payments from AstraZeneca, Bayer, Boehringer Ingelheim, BRAHMS, Chugai, Grünenthal, Helsinn, Hexal, Novartis, Pharmacosmos, Respicardia, Roche, Servier, Sorin, and Vifor;and reports research support from Amgen, AstraZeneca, Boehringer Ingelheim, IMI, and the German Center for Cardiovascular Research (DZHK). JB is a consultant to Abbott, American Regent, Amgen, Applied Therapeutic, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardiac Dimension, Cardior, CVRx, Cytokinetics, Daxor Edwards, Element Science, Innolife, Impulse Dynamics, Imbria, Inventiva, Lexicon, Lilly, LivaNova, Janssen, Medtronics, Merck, Occlutech, Owkin, Novartis, Novo Nordisk, Pfizer, Pharmacosmos, Pharmain, Prolaio, Roche, Secretome, Sequana, SQ Innovation, Tenex, and Vifor. SDA reports grants and personal fees from Abbott Vascular and Vifor, and personal fees for consultancies, trial committee work and/or lectures from Actimed, Amgen, Astra Zeneca, Bayer, Boehringer Ingelheim, Bioventrix, Brahms, Cardiac Dimensions, Cardior, Cordio, CVRx, Cytokinetics, Edwards, Faraday Pharmaceuticals, GSK, HeartKinetics, Impulse Dynamics, Novartis, Occlutech, Pfizer, Repairon, Sensible Medical, Servier, Vectorious, and V-Wave.
This encore abstract was originally presented at European Society of Cardiology (ESC) Congress 2024 (London, UK/Hybrid; Aug 30–Sept 2, 2024)
20First Demonstration by Cardiac Computed Tomography that Elevated Lipoprotein(a) is Associated with High-Risk Partially Calcified Plaque, Extensive Plaque Burden, and Luminal Stenosis, Independent of Apolipoprotein B Levels
Szilard Voros(1), Wess Boatwright(2), Mahmoud Al Rifai(3), Marc R. Dweck(4), Bradley O. Brown(1), David S Watson(5), Anthony Lozama(2), Denise P. Yates(6), Sarah Rinehart(7), Arshed A Quyyumi(8)
- G3 Therapeutics, Midlothian, VA, USA; 2. Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 3. Houston Methodist Hospital, Houston, TX, USA; 4. Centre for Cardiovascular Science University of Edinburgh, Scotland, UK; 5. King’s College London, London, UK; 6. Novartis, Biomedical Research, Cambridge, MA, USA; 7. Charleston Area Medical Center, Charleston, WV, USA; 8. Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine, Atlanta, GA, USA.
Purpose: Elevated lipoprotein(a) [Lp(a)] is a prevailing genetic cause of coronary artery disease (CAD). Previous retrospective and prospective angiographic imaging studies have shown that elevated Lp(a) levels drive the progression of high-risk plaque phenotypes and are associated with extensive plaque burden and increased risk of luminal stenosis. In addition, increasing evidence suggests that Lp(a) is a driver of premature cardiovascular events. We hypothesize that Lp(a)-driven CAD, defined as CAD in the presence of elevated Lp(a) regardless of other lipid/lipoprotein parameters, represents a unique, high-risk phenotype compared with non-Lp(a)-driven CAD. The Genetic Loci and the Burden of Atherosclerotic Lesions (GLOBAL) study (NCT01738828) utilized multi-omic analyses and deep phenotyping of coronary atherosclerosis by coronary computed tomography angiography (CCTA) to unravel the underlying pathology of atherosclerotic CAD. The ongoing Lp(a) sub-analysis of the GLOBAL study aims to provide evidence supporting the causal role of Lp(a) in cardiovascular disease. The objective was to determine from the qualitative analysis the prevalence of high-risk (partially calcified plaque [PCP]) versus lower-risk (non-calcified plaque [NCP] and calcified plaque [CAP]) plaques, coronary plaque burden, and risk of luminal stenosis in patients with elevated Lp(a).
Methods: We analyzed data from patients enrolled in the GLOBAL clinical study who were referred for coronary CCTA for suspected CAD. Lp(a) mass was measured using a latex enhanced immunoturbidimetric assay, Lp(a) molar concentration (nmol/L) was measured by isoform-independent enzyme-linked immunosorbent assay, and Lp(a) cholesterol was assessed by gel electrophoresis. Lp(a) kringle IV (KIV)2 repeats and percentage of small vs large apo(a) isoforms (≤24 KIV2 vs >24 KIV2 repeats) were measured by western blot. Apolipoprotein B (ApoB) was measured by an antigen–antibody reaction via a turbidimeter. Coronary plaque type, plaque burden, and prevalence of obstructive luminal stenoses (≥70%) were assessed by CCTA. Plaque type was evaluated using the modified American Heart Association 17-segment classification and defined as NCP, PCP, or CAP in each segment using Coronary Artery Disease-Reporting and Data System 2.0 visual qualitative classification. Measures of plaque burden, i.e., segment involvement score (SIS) and computed tomography (CT)-Leaman score, were calculated for each patient. Statistical associations between Lp(a) measurements and number of NCP, PCP, and CAP per patient, as well as coronary plaque burden were determined by Pearson’s correlation. Lp(a) measurements were compared across patients with predominant NCP, PCP, or CAP by analysis of variance (ANOVA). CT-Leaman score was compared across Lp(a) quartiles (Q) by ANOVA. The association between Lp(a) measurements and luminal stenosis was determined by Welch’s t test. The effect of Lp(a) measurements conditioned on ApoB was determined by a generalized covariance test.
Results: Overall, 340 patients were included (53% female; mean age±SD 55.6±9.8 years; median Lp(a) 24.9 [IQR 73.3] nmol/L; median Lp(a) mass 11.0 [IQR 22.1] mg/dL). Of included patients, 62% had ‘normal’/non-obstructive plaque, 10% had 1-vessel disease (VD), 2% had 2-VD, 17% had 3-VD, and 9% had 4-VD. Effects on plaque type: Lp(a) molar concentration, Lp(a) mass, Lp(a) cholesterol, and small apo(a) isoforms were significantly associated with PCP (rho 0.153, P=0.005; rho 0.176, P=0.001; rho 0.179, P=0.001; rho 0.163, P=0.003, respectively) but not with NCP or with CAP. In patients with predominantly PCP versus NCP or CAP, Lp(a) cholesterol (4.27, 3.79, and 3.4 mg/dL, respectively; one-sided ANOVA P=0.018) and small apo(a) isoforms (10.29, 3.68, and 2.77 nmol/L, respectively; one-sided ANOVA P=0.02) were significantly higher. Effects on plaque burden: SIS was significantly correlated with Lp(a) molar concentration (rho 0.16, P=0.003), Lp(a) mass (rho 0.18, P=0.001), Lp(a) cholesterol (rho 0.16, P=0.003), and small apo(a) isoforms (rho 0.14, P=0.009). CT-Leaman score was significantly correlated with Lp(a) mass whether expressed as a continuous variable (rho 0.17, P=0.002) or Lp(a) mass quartiles (ANOVA P=0.03). Effects on luminal stenosis: Patients with ≥70% (n=71, 21%) vs <70% (n=269, 79%) luminal stenosis had significantly higher Lp(a) molar concentration (44.75 vs 22.1 nmol/L, respectively; ANOVA P=0.015), small apo(a) isoforms (8.74 vs 4.18 nmol/L, respectively; ANOVA P=0.034), Lp(a) mass (17.8 vs 10.39 mg/dL, respectively; ANOVA P=0.011) and percentage of ApoB carried by Lp(a) particles (3.8% vs 3.2%, respectively; ANOVA P=0.004). When modeled over the range of ApoB (27.15–184.05 mg/dL), the association between Lp(a) and coronary plaque was strongest for PCP (rho 0.248, P<0.001) versus NCP or CAP, Lp(a) mass was a significant predictor of CT-Leaman score (rho 0.75, P<0.001), and Lp(a) molar concentration, Lp(a) mass, and small apo(a) isoforms were associated with ≥70% stenosis (rho 0.8, 1.0, and 1.0, respectively).
Conclusions: In this analysis of patients referred for CCTA for suspected CAD, elevated Lp(a) was significantly associated with PCP, the highest-risk qualitative plaque phenotype, and not the lower-risk NCP or CAP phenotypes. Elevated Lp(a) was also associated with extensive coronary plaque burden as well as increasing prevalence of obstructive CAD, independent of ApoB levels. Since PCP is most strongly associated with adverse cardiovascular events compared with lower-risk plaque phenotypes, our study provides novel insight that Lp(a) may drive premature cardiovascular events through its association with high-risk PCP phenotypes. These findings are consistent with the hypotheses that Lp(a)-driven CAD is characterized by more extensive plaque burden vs non-Lp(a)-driven CAD and that Lp(a)-driven CAD is a unique and high-risk CAD phenotype for any level of circulating ApoB. The Lp(a) sub-analysis of the GLOBAL study is ongoing to identify phenotypic features indicative of high risk in patients with Lp(a)-driven CAD, including those who may be eligible for treatment with investigational Lp(a) lowering therapies in the future.
Disclosures: SV and BOB are employees of G3 therapeutics, Midlothian, VA, USA; WB, DPY and AL are employees of Novartis; DSW, MR, and SR have nothing to disclose; MRD has received speaker fees from Pfizer, Radcliffe Cardiology, Amarin, Bristol Myers Squibb, Edwards and Novartis and has received consultancy fees from Novartis, Jupiter Bioventures, AstraZeneca, Beren and Silence therapeutics; AAQ has received grants from the National Institutes of Health. This study is sponsored by Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA. Medical writing support was provided by Kayleigh Bassiri, PhD, of BOLDSCIENCE Ltd., and was funded by Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA, in accordance with GPP 2022 guidelines. The authors had full control of the content and made the final decision on all aspects of this publication.
10Health Outcomes and Incidence of Diabetes Among Patients With Severe Hypertriglyceridemia and Acute Pancreatitis
Michael S. Broder, MD, MSHS,1; Eunice Chang, PhD,1; Kathleen F. Villa, MS,2; Nathan D. Wong, PhD, MPH3
1: PHAR (Partnership for Health Analytic Research, LLC), Beverly Hills, CA, USA; 2: Ionis Pharmaceuticals, Carlsbad, CA, USA; 3: University of California, Irvine, School of Medicine, Irvine, CA, USA
Purpose: Patients with severe hypertriglyceridemia (sHTG), in particular triglyceride levels ≥500 mg/dL, are at increased risk for acute pancreatitis (AP). Pancreatitis can itself lead to type 2 diabetes mellitus (T2DM), but the strength of this association in patients with sHTG is unknown. We undertook this analysis to determine the extent to which non-diabetic patients with sHTG-AP have an increased incidence of new-onset T2DM compared to similar patients with sHTG alone.
Methods: In a retrospective cohort study conducted in a large, nationally representative healthcare claims database, we identified adults with sHTG (triglyceride (TG) levels 500-15,000 mg/dL) with AP (ICD-9-CM: 577.0;ICD-10-CM: K85.xx excluding K85.2 and K85.3) between January 2013 – December 2021. Propensity score and exact matching were conducted to identify patients with sHTG without AP in a 1:1 ratio. The propensity for sHTG-AP was estimated using a logistic regression model which included sociodemographics, insurance, comorbidities, statin and non-statin lipid-lowering medication use, GLP-1 use, index TG value, and total cholesterol. Patients were also exactly matched on index TG value categories (500-879, 880-999, 1000-1999, 2000-15000 mg/dL), and index year using the greedy nearest neighbor method with caliper width of 0.2 of the standard deviation of the logit of the propensity score. All patients with T2DM at baseline were excluded as were sHTG-AP patients without a match. All patients were continuously enrolled 1 year prior to index date (baseline) and were followed for at least 6 months (unless died earlier), either until the end of enrollment or study end (12/31/2022). The risk of incident T2DM (≥2 claims with T2DM diagnosis ≥30 days apart) was compared between sHTG-AP and sHTG alone cohorts using a Cox regression.
Results: There were 330 matched pairs of patients with sHTG-AP and sHTG alone without T2DM at baseline. The mean (SD) age of patients with sHTG-AP was 51.1 (13.0) years and 50.1 (12.6) years for patients with sHTG alone. Both sHTG-AP and sHTG alone groups were comprised of 29.7% (n=98) females. The majority of patients with sHTG-AP and sHTG alone were White, 63.0% (n=208) and 60.9% (n=201), respectively, and most had commercial health insurance, 73.0% (n=241) and 77.3% (n=255), respectively. Baseline mean (SD) index TG was 1,053.1 (934.4) mg/dL for sHTG-AP and 994.4 (838.2) mg/dL for sHTG alone.
Other risk factors, including mean (SD) cholesterol, were similar between sHTG-AP at 264.4 (121.9) mg/dL and sHTG alone at 255.8 (105.4) mg/dL at baseline. All baseline measures were not significantly different between cohorts (p>0.05). The follow-up period lasted a mean (SD) of 3.0 (2.2) years for sHTG-AP and 2.9 (2.1) years for sHTG alone (p=0.876). Over the follow-up, the incidence of new onset T2DM was 27.9% in the sHTG-AP group compared to 11.2% in those with sHTG alone (p <0.001). The risk of T2DM was higher (HR=2.8; p<.001) throughout follow-up in the sHTG-AP group compared to the group with sHTG alone.
Conclusions: Among patients with sHTG, an episode of AP is associated with more than double the incidence of new-onset T2DM compared to patients without AP. Preventing initial episodes of AP may have important health benefits, including the reduction of incident diabetes.
Disclosures: Funding Support: This study was funded by Ionis Pharmaceuticals. MSB: MSB is an employee of PHAR, which was paid by Ionis Pharmaceuticals to conduct the research described in the abstract. PHAR also discloses financial relationships with the following entities outside of the submitted work: AbbVie, Akcea, Amgen, AstraZeneca, BioMarin Pharmaceuticals, Bristol-Myers Squibb, Boston Scientific Corporation, Eisai, Ethicon, Genentech, Gilead, Novartis, Otsuka, Pfizer, Recordati, Regeneron, Sanofi US Services, Sunovion, Takeda Pharmaceuticals USA. EC: EC is an employee of PHAR, which was paid by Ionis Pharmaceuticals to conduct the research described in the abstract. PHAR also discloses financial relationships with the following entities outside of the submitted work: AbbVie, Akcea, Amgen, AstraZeneca, BioMarin Pharmaceuticals, Bristol-Myers Squibb, Boston Scientific Corporation, Eisai, Ethicon, Genentech, Gilead, Novartis, Otsuka, Pfizer, Recordati, Regeneron, Sanofi US Services, Sunovion, Takeda Pharmaceuticals USA. KFV: KFV reports the following: support for the present abstract: Ionis Pharmaceuticals; KFV is an employee and shareholder of Ionis Pharmaceuticals. NDW: NDW reports the following: support for the present abstract: Ionis Pharmaceuticals; consulting fees: Ionis Pharmaceuticals; research support through institution from Regeneron, Novartis, and Novo Nordisk; consultant for Amgen, Novartis, and HeartLung.
1Need of Lifestyle Medicine Program on Cardiometabolic Patients
AG Palladino-Davis, Erik Meyer, Anthony Pick
Northwestern University
Purpose: A healthy lifestyle is not a short stint overhaul to a better health, to maintain sustainability a life-cycle continuum is necessary to reap the benefits and decrease morbidity and early mortality. Patients with multiple co-morbidities are in an innate position requiring ongoing healthcare access and services. We focused on this Cardiometabolic patients to leverage and centralize the existing Northwestern Medicine Lake Forest Hospital community resources and intentionally provide referral services for these to improve the health of this patient population via a Quality Improvement Lifestyle Medicine (LM) program, which to our knowledge is the first of its kind at Northwestern healthcare system in the Chicago metropolitan area.
Methods: We recruited 100 patients from the endocrine and cardiology clinics with a history including but not limited to: hypertension, hyperlipidemia, obesity, pre-diabetes, diabetes, sleep apnea, self-identified trouble sleeping, patients requiring social support/social connectedness, those having identified risky substance use, and/or those wanting to improve their physical activity. Once identified as meeting criteria for the program and recruited, the patients were administered the American College of Lifestyle Medicine (ACLM) long-version questionnaire as a screening tool scoring daily lifestyle habits that impact health. The results of the hour long questionnaire were used to make referrals and a plan outlining course of treatment where appropriate.
Results: Our program provided an opportunity to refer and prescribe the need for lifestyle medicine. We found that 100% of the patients required complex care coordination and had been receiving fragmented care despite the multitude number of lifestyle medicine related services available within our healthcare system. Chronic conditions are the leading cause of death and disability in the world and 80% of healthcare spending in the United States. Inherently, complex cardiometabolic patients provide a window into healthcare and the healthcare system where we would not have access to the lifestyle gaps and needs of these patients otherwise. There were on average 4-5 referrals per patient and 100% of the patients were referred for further care. This involved connecting patients to registered dietitians on staff, recruitment to the health and fitness center, sports medicine, physical therapy, and sleep medicine when appropriate.
The psycho-social components including but are not limited to social relationships, stress, avoidance of risky substances, and trauma are under the direction of a social worker and/or Psych D. Furthermore, making use of already existing free services through the Alberto Culver Health Learning Center and culinary medicine via the Leishman Center for Culinary Health. Our pilot program provided us the opportunity to demonstrate the fragmented care within such a large healthcare system, and the results have initiated a unification of resources and referrals for establishing a Lifestyle Medicine program to service the five regions that make up the entirety of the health system. The current cardio-renal-metabolic registry pulls 5160 patients that meet criteria for Cardiometabolic health and inherently LM program and this number is only reflective of patients that have an appointment in the system in the next 30 days. The population health potential to improve and even reverse chronic conditions is thus rather significant.
Conclusions: Capturing complex cardiometabolic patients during a vulnerable time in their health journey allows for an innate sustainable investment in their health and well-being. One of the goals being helping patients control and mitigate (and at times reverse) secondary effects of chronic conditions. Importantly, a comprehensive lifestyle medicine approach to patient care identifies the tangible impacts of social determinants of health on patient’s lives, thus allowing public health professional’s to better protect, promote, and restore their health. This is imperative as social determinants of health are known to play a role in health outcomes and thus the need to provide precision medicine to an already in need population. At the epigenetic level, lifestyle implications due have an impact on health and well-being of the current population and even future offsprings. Operationalizing LM allows for improved outcomes in the Cardiometabolic patient population, but also it has the capacity to impact future generations by reducing cardiometabolic disease predisposition.
Disclosures: Nothing to disclose by any authors at the time of this submission.
6Negative Correlation between Low-Density Lipoprotein Cholesterol/High-Density Lipoprotein Cholesterol (LDL-C/HDL-C) Ratio and Neutrophil/Lymphocyte Ratio (NLR) in ST-Elevation Myocardial Infarction Patients
Bratasena Sally, Aman Nasution, Ika Presetya Wijaya, Simon Salim, Cleopas Martin Rumende, Hamzah Shatiri, Anna Mira Lubis
Department of Internal Medicine, Faculty of Medicine, University of Indonesia
Purpose: ST-Elevation Myocardial Infarction (STEMI) is one of the coronary syndromes that contributes to a high mortality rate, particularly in the first 30 days due to complete coronary artery occlusion, leading to myocardial ischemia and subsequent necrosis. Cholesterol and inflammation remain at the forefront of the atherosclerotic plaque etiopathogenesis in this acute coronary syndrome. They have a complex interplay in plaque narrowing or stenosis formation and plaque rupture that can cause thrombus formation. These two key players could be described with LDL-C/HDL-C ratio the atherogenic index and NLR the inflammatory index respectively. But the overall mechanism is not yet fully understood and limited data exist regarding study the correlation of these two key players in STEMI patients. This study aimed to assess the correlation between the LDL-C/HDL-C ratio (the atherogenic index) and NLR (the inflammatory index) in STEMI patients.
Methods: This study was conducted using a cross-sectional design. A total of 99 STEMI patients with Killip classification I/II who underwent primary PCI and met the inclusion and exclusion criteria were enrolled from the cardiac catheterization laboratory at Dr. Cipto Mangunkusumo National Hospital in Indonesia.
Clinical profiles, emergency blood tests, and coronary angiography data were collected. Correlation analysis was performed using the Spearman test. The correlation Analysis was further analyzed based on stenosis severity or Gensini score (the Gensini score, calculated from angiographic data, was divided into three tertiles: Tertile I: ≤27, Tertile II: 28–60, and Tertile III: ≥61, representing mild, moderate, and severe plaque stenosis, respectively).
Results: A significant negative correlation was observed between the LDL-C/HDL-C ratio and NLR (r = -0.262, p = 0.009). This negative correlation was consistently observed in each tertile of STEMI patients, although statistical significance was found only in Tertile I, which had the highest inflammation index in this study (Tertile I: r = -0.445, p = 0.009;Tertile II: r = -0.035, p = 0.851;Tertile III: r = -0.290, p = 0.097).
Conclusions: A negative correlation exists between the LDL-C/HDL-C ratio (the atherogenic index) and NLR (the inflammatory index) in STEMI patients. Higher NLR is associated with a stronger inverse correlation with the LDL-C/HDL-C ratio.
Disclosures: Nothing to disclose by any author(s).
8Obicetrapib Targets all Atherogenic Lipoproteins Beyond LDL-C
Michael H. Davidson1, Christie M. Ballantyne2, Andrew Hsieh1, Jeremy Smart1, Marc Ditmarsch1, Douglas Kling1, Danielle Curcio1, Mary R. Dicklin3, John J.P. Kastelein1
1 NewAmsterdam Pharma, Naarden, The Netherlands, 2 Baylor College of Medicine, Houston, TX, U.S, 3 Midwest Biomedical Research, Addison, IL, U.S.
Purpose: Despite reductions in low-density lipoprotein cholesterol (LDL-C) with statin and non-statin lipid-lowering therapies, a large proportion of cardiovascular disease (CVD) risk remains. An investigation of 8 large CV outcome trials with statins demonstrated, on average, a relative risk reduction of 25%, leaving the majority of risk unaddressed. Residual risk is due in part to lipid components beyond LDL-C, such as LDL particle (-P) concentration, small dense (sd)LDL-C, and lipoprotein(a) [Lp(a)]. Obicetrapib is a cholesteryl ester transfer protein inhibitor under investigation for reducing atherogenic lipoproteins and CVD events.
Methods: ROSE1 (n=120) and ROSE2 (n=119) were phase II trials of obicetrapib on top of high-intensity statins for 8 or 12 weeks and TA-8995-203 (n=102) was a phase II trial of obicetrapib on top of atorvastatin 10/20 mg or rosuvastatin 5/10 mg for 8 weeks in Japanese participants. All trials enrolled men and women without CVD who had LDL-C >70 mg/dL;all included a treatment arm of obicetrapib 10 mg monotherapy. Additionally, ROSE2 combined obicetrapib 10 mg with ezetimibe 10 mg. A complete lipid profile and apolipoprotein (Apo) B were measured in all trials. Additionally, Lp(a) was measured in ROSE1 and ROSE2, and sdLDL-C and nuclear magnetic resonance-assessed lipoprotein subfractions were analyzed in ROSE2.
Results: In addition to significantly lowering LDL-C by up to 50.8%, Apo B by up to 29.8%, and non-HDL-C by up to 44.4%, in ROSE2 obicetrapib 10 mg monotherapy compared to placebo significantly decreased total LDL-P, small LDL-P, and sdLDL-C by 54.8%, 92.7%, and 30.9%, respectively. A pooled analysis of Lp(a) demonstrated a placebo-corrected reduction of 57.1%. Obicetrapib plus ezetimibe also significantly reduced total LDL-P (-72.1%), small LDL-P (-95.4%), and sdLDL-C (-44.4%), beyond its significant effects on LDL-C (-63.4%), non-HDL-C (-55.6%), and Apo B (-34.4%). Obicetrapib had an adverse event profile similar to placebo, and it was nearly completely eliminated from circulation within 4 weeks after dosing.
Conclusions: By reducing atherogenic lipoproteins beyond LDL-C, obicetrapib monotherapy on top of statins and in combination with ezetimibe represents a promising therapy to address residual lipoprotein-related risk for CVD on top of currently available LDL-C-lowering therapies.
Disclosures: Michael H. Davidson (lead author) is Chief Executive Officer for NewAmsterdam Pharma;Christie M. Ballantyne (lead investigator) has received grant/research support (through his institution) from Abbott Diagnostics, Akcea, Amgen, Arrowhead, Esperion, Ionis, Merck, NewAmsterdam Pharma, Novartis, Novo Nordisk, Regeneron, and Roche Diagnostic;and consulting fees from Abbott Diagnostics, Alnylam Pharmaceuticals, Althera, Amarin, Amgen, Arrowhead, AstraZeneca, Denka Seiken, Esperion, Genentech, Gilead Illumina, Matinas BioPharma Inc., Merck, NewAmsterdam Pharma, Novartis, Novo Nordisk, Pfizer, Regeneron, Roche Diagnostic, and TenSixteen Bio.
3Patient and Cardiologist Perspectives on the Treatment of Atherosclerotic Cardiovascular Disease and Obesity
Pam Taub1, Lyn Behnke2,3,4, Michael Knight5, Delilah McCarty6, Carey Robar6, Andrea Traina6
1: University of California San Diego, San Diego, CA, USA;2: WomenHeart, Washington, DC, USA;3: University of Michigan-Flint, Flint, MI, USA;4: Saginaw Valley State University, University Center, MI, USA;5: The George Washington University, Washington, DC, USA;6: Novo Nordisk, Inc., Plainsboro, NJ, USA
Purpose: Though an association between health outcomes and obesity in patients with atherosclerotic cardiovascular disease (ASCVD) has been known for decades, there are no focused studies on patient/caregiver and healthcare provider (HCP) perspectives and experiences with ASCVD and obesity. This study aimed to gain insight into treatment perspectives from patients with ASCVD and obesity or overweight (body mass index [BMI] ≥27 kg/m2) and the cardiology HCPs who treat them.
Methods: This was a 2-part study;part 1 included a qualitative online survey of patients (N=61) and caregivers (N=12) and interviews with patients (N=61), caregivers (N=12), and HCPs (N=24). Part 2 was a quantitative online survey of cardiology HCPs (N=120).
Results: Patient respondents were 45-59 years (51%) or ≥60 years (49%) old and were Black/African American (38%), White (29%), Latinx (20%), Asian (10%), or mixed race (3%). All patients had ≥1 ASCVD event and 66% had been diagnosed with obesity. While 70% of patients thought excessive weight was the main risk factor for an ASCVD event, many noted a lack of communication with HCPs regarding the link between obesity and cardiovascular health. Patients reported that HCPs gave vague advice on diet/exercise and did not take cultural differences into account when creating treatment plans.
HCP respondents were board-certified cardiologists (83%), cardiology nurses (15%), and cardiology nurse practitioners (2%). Despite HCPs reporting that 43% of their patients have BMI >30 kg/m2, they ranked obesity as only the 4th most important parameter to monitor pre- and post-ASCVD and 53% believe other HCPs should lead the management of obesity, primarily referring patients back to primary care providers. Despite new therapies, only 12% of cardiology HCPs recommended medication to treat obesity. Over 90% of cardiology HCPs recommended changes to diet/exercise pre- and post-ASCVD but admitted to rarely customizing recommendations due to lack of time.
Conclusions: Cardiology HCPs acknowledge obesity as a risk factor for ASCVD, but medical management of obesity is not prioritized. HCPs are hesitant to prescribe anti-obesity medications as part of a treatment regimen despite new treatment options. Despite obesity being a known driver of cardiovascular disease and the availability of safe and effective medications approved for chronic weight management, cardiology healthcare providers remain hesitant to provide medical management for this ASCVD risk factor. Treating obesity with medication is an important step in a holistic treatment plan for ASCVD. Cardiologists and primary care clinicians must collaborate on this complex problem.
Disclosures: This study was sponsored by Novo Nordisk. Pam Taub: Consultant to Sanofi, Novo Nordisk Inc., Novartis, Boehringer-Ingelheim, Amgen, Bayer, Medtronic, Jazz, Edwards, and Esperion;Founder and shareholder of Epirium Bio. Lyn Behnke: Consultant to Novo Nordisk, Inc. Michael Knight: Consultant to Novo Nordisk, Inc. and Gilead Sciences, Inc. Delilah McCarty, Carey Robar, Andrea Traina: Employed by Novo Nordisk, Inc.
18Phase 3 randomised, placebo-controlled ESSENCE trial of semaglutide 2.4 mg in participants with non-cirrhotic non-alcoholic steatohepatitis: baseline characteristics, impact of new metabolic dysfunction-associated steatotic liver disease criteria and non-invasive tests
Philip N. Newsome1, Elisabetta Bugianesi2, Vlad Ratziu3, Mary E. Rinella4, Michael Roden5, 6, 7, Kristiane A. Engebretsen8, Iris Kliers8, Christin Rogers Marks9, Laura Østergaard8, Denise Vanni8, Jeppe Zacho8, Arun J. Sanyal10
1 National Institute for Health Research, Birmingham Biomedical Research Centre at University Hospitals Birmingham NHS Foundation Trust, Centre for Liver & Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom; 2 Department of Medical Sciences, University of Turin, Turin, Italy; 3 Sorbonne Université, Institute for Cardiometabolism and Nutrition, Hospital Pitié-Salpêtrière, INSERM UMRS 1138 CRC, Paris, France; 4 Department of Medicine, University of Chicago, Chicago, IL, United States; 5 Department of Endocrinology and Diabetology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany; 6 German Center for Diabetes Research, Partner Düsseldorf, München-Neuherberg, Germany; 7 Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany; 8 Novo Nordisk A/S, Copenhagen, Denmark; 9 Novo Nordisk Inc., Plainsboro, NJ; 10 Stravitz-Sanyal Institute for Liver Disease and Metabolic Health, VCU School of Medicine, Richmond, VA, United States
Purpose: We report the baseline characteristics of participants randomised in the Phase 3 ESSENCE trial of the glucagon-like peptide-1 analogue, semaglutide 2.4 mg subcutaneous once weekly (OW) for non-cirrhotic metabolic dysfunction-associated steatohepatitis (MASH).
Methods: ESSENCE (NCT04822181) is an ongoing 247-week Phase 3, randomised trial. Following a 14-week screening phase, 800 participants (part 1) of 1200 planned (part 2) with MASH and fibrosis stages 2/3 (F2/F3) were randomised 2:1 to receive semaglutide 2.4 mg subcutaneous OW or placebo OW added to standard of care. In part 1, the two primary endpoints at 72 weeks are resolution of steatohepatitis and no worsening of liver fibrosis, and improvement in liver fibrosis and no worsening of steatohepatitis. Based on a central pathologist evaluation, inclusion criteria were histological presence of steatohepatitis stages F2/F3 per the Nonalcoholic Steatohepatitis Clinical Research Network classification, and a non-alcoholic fatty liver disease activity score (NAS) of ≥ 4, with a score of ≥ 1 in steatosis, lobular inflammation and hepatocyte ballooning.
Results: 800 participants (250 F2;550 F3) were randomised. Mean (SD) age was 56 (11.6) years;57.1% were female;≥ 99% had ≥ 1 cardiometabolic risk factor(s) in accordance with the metabolic dysfunction-associated steatotic liver disease (MASLD) definition. Mean (SD) NAS was 5.05 (0.95), and higher in F3 versus F2 (5.11 [0.95] vs 4.92 [0.93], respectively). Notably, participants with a higher NAS had more cardiometabolic risk factors for MASLD (52.9% with NAS ≥ 5 vs 45.3% with NAS 4). Similarly, a greater proportion of participants with F3 had all five cardiometabolic risk factors versus F2 (52.9% vs 44.8%, respectively). Although cardiometabolic comorbidities were highly prevalent, 44.5% of participants did not have type 2 diabetes (T2D), and 27.3% did not have obesity.
Normal liver transaminases were observed in 26.3% of participants (28% F2;26% F3). Mean (SD) FibroScan liver stiffness was 12.8 (6.9) kPa, and values of < 8 kPa were observed in 15.3% of participants. Mean (SD) controlled attenuation parameter value was 329 (46) dB/m;mean (SD) enhanced liver fibrosis (ELF) score was 10.0 (1.0), and 43.5% of participants had an ELF score of < 9.8. Overall, 8.8% and 9.0% of participants with/without T2D did not meet any of the following non-invasive criteria: Fibrosis-4 index ≥ 1.3, vibration-controlled transient elastography ≥ 8.1, or ELF ≥ 9.8, and more participants with F2 (14.7–16.4%) did not meet these criteria versus F3 (4.5–6.7%).
Conclusions: The ESSENCE baseline population includes participants with significant fibrosis (F2 and F3) and approximately 91% of the trial population had ≥ 1 positive diagnostic non-invasive test. Cardiometabolic risk factors were found in ≥ 99% of participants, and in increased numbers in those with higher NAS and fibrosis stages.
Disclosures: This research was funded by Novo Nordisk A/S. Submission support was funded by Novo Nordisk Inc. (Plainsboro, NJ, USA). PNN: reports grants from Novo Nordisk, and has received consulting fees from Novo Nordisk, Boehringer Ingelheim, Gilead, Intercept, Poxel Pharmaceuticals, Bristol Myers Squibb (BMS), Pfizer, Sun Pharma, Madrigal and GSK. PNN also reports honoraria as a speaker for Novo Nordisk and AiCME;support for attending meetings for Novo Nordisk;and participation on an advisory board for Novo Nordisk, Boehringer Ingelheim, Gilead, Intercept, Poxel Pharmaceuticals, BMS, Pfizer, Sun Pharma, Madrigal and GSK. EB: served as a consultant or advisory board member for Boehringer Ingelheim, Gilead, Intercept, Merck, Novo Nordisk, Pfizer, ProSciento, and as a speaker for Gilead, Intercept, Merck, Novo Nordisk and Pfizer. EB has also received a research grant from Gilead for fatty liver research. VR: received consulting fees from Novo Nordisk, Sagimet, Madrigal, Enyo, Poxel, Northsea, Intercept and ProSciento, and research grants (to institution) from Gilead and Intercept. MER: consults for Boehringer Ingelheim, CytoDyn, GSK, Novo Nordisk, HistoIndex, Intercept, Madrigal, NGM Bio, and Sonic Incytes. MR: reports grants from Boehringer Ingelheim and Novo Nordisk, and has received fees for consulting or participation in advisory boards for Boehringer Ingelheim, Echosens, Eli Lilly and Novo Nordisk. MR also reports honoraria as a speaker for AstraZeneca, Boehringer Ingelheim, Novo Nordisk and Madrigal. AJS: consults for and advises Avant Santé and AstraZeneca. AJS also consults for and has received grants from Akero, BMS, Intercept, Eli Lilly, Madrigal and Novo Nordisk. AJS consults for and owns stock in Rivus, and also consults for AGED Diagnostics, Albireo, Alnylam, Altimmune, Boehringer Ingelheim, 89Bio, Echosens, Genentech, Gilead, GSK, HistoIndex, Mallinckrodt , Merck, NGM Bio, Novartis, PathAI, Pfizer, Poxel, Regeneron, Salix, Siemens, Surrozen, Takeda, Terns and Zydus. AJS owns stock in Durect, Exalenz, Genfit, Indalo, Inversago and Tiziana, and has received royalties from Elsevier and Wolters Kluwer. CRM: is an employee and shareholder of Novo Nordisk Inc. KAE, IK, LHØ, DV and JZ: employees and stockholders of Novo Nordisk A/S.
16Prevalence, Incidence, and Definition of Severe Hypertriglyceridemia: A Comprehensive Review and Weighted Summary
Alexis Baass (1,2), Martine Paquette (2), Otto Lam (3), Kimberly Hofer (3), Jun Collet (3), Monica McClain (4)
1) McGill University Health Centre (MUHC), Montreal, QC, Canada; 2) Lipids, Nutrition, and Cardiovascular Prevention Clinic of the Montreal Clinical Research Institute, Montreal, QC, Canada; 3) Evidinno Outcomes Research Inc., Vancouver, BC, Canada; 4) Ionis Pharmaceuticals, Carlsbad, CA, United States
Purpose: Hypertriglyceridemia (HTG) is characterized by elevated plasma triglycerides (TGs), which pose significant health risks, including pancreatitis and atherosclerotic cardiovascular disease. HTG can be primary, with a genetic basis, or secondary/acquired due to contributing conditions such as obesity, uncontrolled diabetes, alcohol abuse, physical inactivity, metabolic syndrome, hypothyroidism, and certain medications. Clinical practice guidelines vary in their definitions of severe hyperglyceridemia (sHTG) based on TG levels, affecting prevalence and incidence estimates. Consequently, the current epidemiology of sHTG in the general population remains uncertain. This literature review aimed to summarize the definitions of sHTG in clinical practice guidelines and synthesize data on its prevalence and incidence among the general adult population across various countries and settings.
Methods: A comprehensive literature review was performed to identify relevant publications by searching Embase and MEDLINE® via OvidSP from database inception to September 27, 2023 using predefined search terms and strategies. Conference abstracts were identified via the primary database search, and additional relevant studies were found by manually reviewing the bibliographies of pertinent literature reviews and key studies. Clinical practice guidelines providing definitions of sHTG and epidemiological studies reporting the prevalence or incidence of primary sHTG (defined by a substantial genetic component or as classified in the publication), using TG thresholds of at least 500 mg/dL (5.6 mmol/L), among adults (age ≥18 years) from any country were included. Studies that did not specify whether sHTG was primary or secondary/acquired, or reported on mixed sHTG (encompassing both primary and secondary/acquired cases; referred to as “unspecified/mixed sHTG”) were also included. Studies reporting on populations which were not representative of the general population (e.g., elderly, pediatric) were excluded. Prevalence estimates were stratified according to sHTG type (primary vs. unspecified/mixed) and TG thresholds: TG >500 mg/dL (>5.6 mmol/L), >886 mg/dL (>10 mmol/L), >1000 mg/dL (>11.2 mmol/L), and other TG thresholds (i.e., less commonly reported). Included studies were assessed for risk of bias. The pooled prevalence of sHTG was calculated after excluding studies with substantial bias. A quantitative analysis using a random-effects model was performed on the logit scale using the restricted maximum likelihood estimator with the metafor package (v4.6-0) in R (v4.4.0). Random-effects estimates were weighted by 1 / (SE2 + 𝜏2), where SE is the standard error for the study and 𝜏2 is the between-study variance. Results were presented in forest plots.
Results: Of the 16,020 records identified, 13 guidelines or consensus documents were selected from the United States (US; n=8), Europe (n=2), India (n=2), and Latin America (n=1). Most guidelines used a TG threshold of ≥500 mg/dL to define sHTG, except one US (threshold of 1000-1999 mg/dL) and two European guidelines (>880 mg/dL). Terminology varied, using terms like “severe”, “very high”, or “distinct”. Fasting was required in US and Indian guidelines, but not in Latin America; European guidelines recommended fasting only for specific cases.
Forty epidemiological studies were included, primarily conducted in the US (n=10), China (n=3) and Italy (n=3). Most studies focused on adults (n=31), with a few involving mixed adult/pediatric populations or not reporting age. TG thresholds for sHTG ranged from ≥500 to ≥2000 mg/dL. A large proportion of studies (n=21/40) used non-representative samples, which were considered to have substantial selection bias and were thus excluded from pooled prevalence estimates.
Prevalence estimates for unspecified/mixed sHTG varied widely. For >500 mg/dL, pooled estimates (% [95% confidence interval]) were 1:159 in Europe (0.63% [0.30–1.33%]), 1:64 in China (1.56% [1.27–1.91]), and 1:58 in the US (1.73% [1.25–2.38]). Pooled prevalence in the US for >886 mg/dL was 1:625 (0.16% [0.08–0.29]), and for >1000 mg/dL in Europe, pooled prevalence was 1:909 (0.11% [0.05–0.24]); there were insufficient data for pooling in other regions.
Data on primary sHTG in population-based studies were limited, with one US study reporting 1:125 (0.80% [0.72–0.87]), and a Spanish study reporting 1:667 (0.15%) for TG >500 mg/dL. Five-year incidence rates also varied (n=3): 1:400 adults in Canada for unspecified/mixed sHTG (TG 886–1771 mg/dL; 2010–2015), 39 per 100,000 person-years in Denmark for unspecified/mixed sHTG (TG >886 mg/dL; 2008–2019), and 24 per 100,000 person-years for primary sHTG (TG >500 mg/dL; 1998–2015) in the US.
Conclusions: This first review and analysis of prevalence data for sHTG highlights a key challenge for researchers: the lack of consensus in the definition and labeling of sHTG across guidelines and epidemiological studies. Varying TG thresholds contribute to inconsistent prevalence and incidence rates in the literature. Additionally, over half of the studies used electronic health records (EHR) or laboratory databases to identify sHTG cases, which presents limitations when estimating prevalence in the general population. These databases primarily capture patients seeking medical care, often with comorbidities such as obesity or cardiovascular disease, making them unrepresentative of the broader, undiagnosed population. Variability in testing conditions (e.g., fasting vs. non-fasting samples) or TG thresholds further complicates diagnosis, leading to inconsistencies. Patients in these databases are frequently tested due to underlying risk factors, introducing ascertainment bias and overrepresenting high-risk individuals. EHRs and lab records may also miss transient cases or those outside the recorded time frame. Included studies defined sHTG using a single TG value; longitudinal studies should be conducted to identify patients with persistently elevated TGs to accurately estimate the prevalence of this population. Additionally, these studies often report sHTG cases only for individuals with recorded TG values, without considering those who were not tested, further skewing the data. As a result, sHTG prevalence in the general population may be over- or underestimated. Furthermore, the distinction between primary and mixed/unspecified sHTG adds complexity, with varying classifications yielding differing rates. There is variability in defining sHTG across both guidelines and studies, and the inconsistency in reported prevalence and incidence rates has hindered our understanding of sHTG epidemiology. Prevalence rates also vary across regions, suggesting potential geographical differences or population characteristics. To improve comparisons of sHTG prevalence and incidence and to establish consistent outcomes, the standardization of nomenclature, definitions, and TG thresholds should be prioritized.
Disclosures: This study was funded by Ionis Pharmaceuticals (Carlsbad, CA, USA). Alexis Baass received research grants from Akcea, Amgen, Astra Zeneca, Fondation Leducq, Fondation Yvan Morin, Merck Frosst, and Sanofi. He has participated in clinical research protocols from Acasti Pharma Inc., Akcea, Amgen, Arrowhead Pharmaceuticals, Astra Zeneca, Ionis Pharmaceuticals Inc., Isis Pharmaceuticals, The Medicines Company, Merck Frosst, Novartis, Pfizer, Regeneron Pharmaceuticals Inc., and Sanofi. He has served on advisory boards and received honoraria for symposia from Akcea, Amgen, and Sanofi. Martine Paquette reports no conflicts of interest. Otto Lam, Kimberly Hofer, and Jun Collet are employed by Evidinno Outcomes Research Inc. (Vancouver, BC, Canada), which was contracted by Ionis Pharmaceuticals (Carlsbad, CA, USA) to conduct this study. Monica McClain is an employee and shareholder of Ionis Pharmaceuticals (Carlsbad, CA, USA).
28Rationale and Design of the MUIR-3 Study: Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Plozasiran in Adults with Hypertriglyceridemia
Christie M. Ballantyne, Robert S. Rosenson, Robert A. Hegele, Stephen J. Nicholls, Ran Fu, Ma’an Muhsin, Jennifer Hellawell, Daniel Gaudet
(CMB) Baylor College of Medicine and the Texas Heart Institute, Houston, TX, USA;(RR) Metabolism and Lipids Program;Mount Sinai Fuster Heart Hospital, Icahn School of Medicine at Mt Sinai, Mount Sinai, New York, NY, USA;(RAH) Robarts Research Institute, London, Ontario, Canada;(SJN) Monash University, Victorian Heart Institute, Melbourne, VIC, Australia;(RF, MM, JH) Arrowhead Pharmaceuticals, Pasadena, CA, USA;(DG) Université de Montréal and ECOGENE 21, Montréal, Québec, Canada
Purpose: Despite available lipid lowering treatments, substantial unmet medical need persists for patients with hypertriglyceridemia (HTG) who remain at high atherosclerotic cardiovascular disease risk due to the presence of triglyceride (TG)-rich lipoproteins (TRLs) and atherogenic remnant cholesterol (RC). Plozasiran, an investigational siRNA therapeutic, inhibits hepatic production of apolipoprotein C3 (APOC3), a key regulator of lipoprotein lipase (LPL)-mediated TG metabolism and clearance. APOC3 inhibition has emerged as a promising therapeutic strategy for reducing residual cardiovascular risk. In a phase 2 study in patients with HTG [defined as TG 150-499 mg/dL, (1.69-5.65 mmol/L)], plozasiran demonstrated durable TG reductions of up to -67% vs placebo, measured 12 weeks after the last dose. The MUIR-3 trial will evaluate the efficacy and safety of plozasiran in patients with moderate HTG.
Methods: MUIR-3 is a phase 3, randomized, double-blind, placebo-controlled, multi-center trial. Key inclusion criteria include mean fasting TG ≥150 mg/dL (≥1.69 mmol/L) and ≤499 mg/dL (≤5.65 mmol/L), at screening. Key exclusion criteria include use of any hepatocyte targeted siRNA treatments that target lipids and/or TG within 1 year (except inclisiran administered at least 4 weeks prior to enrollment), siRNA or ASO within 60 days, and active pancreatitis within 4 weeks of screening. Patients will be counseled through the trial to maintain a stable low-fat diet and maintain background lipid-lowering medications throughout the study.
Results: 1328 adult patients with HTG will be enrolled at multiple sites and countries and randomized 3:1 to receive four quarterly subcutaneous injections of plozasiran 25 mg or matching placebo over a 1-year double-blinded period, followed by a 3-month follow up post-treatment period evaluation.
The randomization will be stratified based on statin use at screening. The primary efficacy endpoint is placebo-adjusted percent change in fasting TG from baseline to month 12 with plozasiran. Secondary endpoints include placebo-adjusted percent change in fasting TG from baseline to month 10 and the percentage of patients achieving fasting TG <150 mg/dL (<1.69 mmol/L) at 10 and 12 months compared to placebo. Adjudicated major adverse cardiovascular event rates, safety and tolerability parameters will be assessed. Percent changes in other lipid and lipoprotein parameters will also be assessed.
Conclusions: MUIR-3 is designed to determine whether the APOC3 siRNA plozasiran, as an add on to standard of care lipid lowering therapy, safely reduces TG levels thereby contributing to decreasing the residual cardiovascular disease risk in individuals with HTG.
Disclosures: CMB reports grants and/or honoraria from Abbott Diagnostic, Akcea, Althera, Amarin, Amgen, Arrowhead, AstraZeneca, Denka Seiken, Esperion, Genentech, Gilead, Illumina, Ionis, Matinas BioPharma Inc, Merck, New Amsterdam, Novartis, Novo Nordisk, Pfizer, Regeneron, Roche Diagnostic, and Sanofi-Synthelabo. Co-Authors RSR reports grant/research support from (all paid to institution, not individual): Amgen, Arrowhead, Novartis, Eli Lilly, Regeneron;consulting fees from Amgen, Arrowhead, CRISPR Therapeutics, Eli Lilly, Lipigon, Novartis, Precision Biosciences, Regeneron, UltraGenyx, Verve;non-promotional speaking fee from Amgen and Kowa;other support from MediMergent, LLC (significant);and is an UpToDate, Inc. stock shareholder (significant). RAH has no disclosures. SJN reports grants and/or honoraria from Akcea, Amarin, Amgen, Anthera, Arrowhead Pharmaceuticals Inc, AstraZeneca, Boehringer Ingelheim, Cerenis, CSL Behring, Eli Lilly, Esperion, InfraReDx, LipoScience, The Medicines Company, Merck, New Amsterdam Pharma, Novartis, Omthera, Resverlogix, Roche, Sanofi-Regeneron, and Takeda. RF, MM, JH are current employees of the sponsor, Arrowhead Pharmaceuticals Inc.;DG reports grants and/or honoraria from Alnylam, Amgen, Arrowhead, AstraZeneca, Boehringer-Ingelheim, CRISPR Therapeutics, Dalcor Pharma, Eli Lilly, Esperion, Ionis, Kowa, Novartis, Pfizer, Regeneron, Sanofi, Ultragenyx and Verve Therapeutics. R Fu, S Melquist, K Modesto, T Chang, and J San Martin are all current employees of Arrowhead Pharmaceuticals
32Remote diabetes monitoring program’s 3-year A1c home-kit outcomes: A retrospective analysis
Wei Lu, PhD; Stefanie Painter, DHEd; Roberta James, MStat; Calvin Wu, MD; Tejaswi Kompala, MD
Teladoc Health
Purpose: Glycated hemoglobin A1c (A1c) is the primary tool for assessing glycemic status reflecting average glycemia over 2-3 months and strongly connected to diabetes complications.[1] The American Diabetes Association (ADA) recommends quarterly A1c testing for individuals with poor glycemic control and semi-annually for those in glycemic control.[1] However, approximately 50% of individuals with diabetes are not meeting A1c testing recommendations.[2] Teladoc Health’s remote diabetes monitoring program (RDMP) uses fingerstick glucose values to estimate A1c (eA1c) to assess improvement overtime, which requires a level of blood glucose (BG) monitoring that may not be recommended by a member’s provider resulting in a subset of the RDMP population as unobservable to demonstrate impact using those methods.[3] At the request of employers and health plans to improve screening adherence recommendations, self-collection A1c home-kits were explored to increase accessibility, remove burden of travel from the individual, and enhance personal accountability for one’s health and improve Healthcare Effectiveness Dava and Information Set (HEDIS) quality measures performance.[4] While previous studies have evaluated glycemic improvement based on eA1c calculated by the Nathan method, established as an appropriate population metric and found to have a positive correlation with home-kit A1c, it is essential to demonstrate RDMP effectiveness with more established testing options.[3,5] Therefore, the objective of this study was to evaluate A1c impact using real-world home-kit data to validate prior findings of Teladoc Health’s RDMP.
Methods: A retrospective analysis of dried blood spot A1c home-kit testing in 6-month intervals from September 2020 to September 2023 of members enrolled in a RDMP was performed. Home-kits were provided to a subset of RDMP members based on an opt-in feature available to employers and health plans who pay for the program. All home-kits were analyzed through CLIA-certified laboratories through the test kit provider and results were available to the member through the test kit provider’s secure portal. Home-kits with valid test results were assigned as baseline, 1-year, 2-year, 3-year, or 4-year outcomes based on range between test date and member’s program activation date. Activation date was defined as date of member’s first registered blood glucose (BG) value from program provided BG meter. Baseline was defined as home-kit result date between 0-90 days after activation date. One-year outcome was defined as home-kit result date between 270-450 days after activation date. Two-year outcome was defined as home-kit result between 630-810 days after activation date. Three-year outcome was defined as home-kit result between 990-1,170 days after activation date. Four-year outcome was defined as home-kit result between 1,350-1,530 days after activation date. Pooled 3-year change in home kit A1c outcomes were based on members with home-kit results for baseline versus 3-year outcome or 1-year versus 4-year outcome with groupings defined by the first available A1c home-kit result. Group 1 included members with A1c <8%, group 2 for members with A1c 8-9%, and group 3 had members with A1c >9%.
Results: Members (N=1,637) with 3-year outcomes were on average 68.6 (SD 10.1) years old and 51.7% female. Group 1 were 68.8 (SD 10.2) years old and 51.4% female, group 2 were 68.8 (SD 10.4) years old and 50.7% female, and group 3 were 65.8 (SD 8.4) years old and 61.4% female. Group 1 (n=1,436) had an average change in A1c of 0.16 (SD 0.83) with 1,309 (91%) of members ending year 3 with an A1c <8%. Group 2 (n=134) had an average change in A1c of –0.75 (SD 1.03) with 94 (70%) of members ending year 3 with an A1c <8%. Group 3 (n=57) had an average change in A1c of –2.12 (SD 1.63) with 35 (61%) of members ending year 3 with an A1c <8%.
Conclusions: This study shows effectiveness and supports the RDMP’s goal of glycemic improvement and sustained control over time to improve member health through behavior change interventions.
Recent evaluation of digital diabetes management solutions performed by the Peterson Health Technology Institute used a threshold of ≥0.5% as clinically meaningful A1c reduction [6], which was exceeded by members in this study with A1c ≥8% over the 3-year period. For the subset of members with A1c reduction ≥1%, this will result in significant reduction of risk and costly complications.[7,8] For members with an initial home-kit indicating moderate control (HbA1c <8%), an increase (0.15%) in A1c over the 3-year period was observed;however, previous studies have reported an annual A1c increase of 0.15% as part of the natural disease progression for those with a controlled status.[8,9] Therefore, the RDMP has demonstrated an ability to delay this natural progression, aligning with previous studies utilizing eA1c, displaying confidence that the RDMP can improve glycemic control over a 3-year period and support health plans in meeting Glycemic Status Assessment for Patients with Diabetes (GSD) as part of the HEDIS quality measures.
Disclosures: All authors were employed at Teladoc Health at the time of study.
References
- American Diabetes Association Professional Practice Committee; 6. Glycemic Goals and Hypoglycemia: Standards of Care in Diabetes—2024. Diabetes Care 1 January 2024; 47 (Supplement_1): S111–S125. https://doi.org/10.2337/dc24-S006
- Imai C, Li L, Hardie RA, Georgiou A. Adherence to guideline-recommended HbA1c testing frequency and better outcomes in patients with type 2 diabetes: a 5-year retrospective cohort study in Australian general practice. BMJ Qual Saf. 2021;30(9):706-714. doi:10.1136/bmjqs-2020-012026
- Nathan DM, Kuenen J, Borg R, Zheng H, Schoenfeld D, Heine RJ; A1c-Derived Average Glucose Study Group. Translating the A1C assay into estimated average glucose values. Diabetes Care. 2008 Aug;31(8):1473-8. doi: 10.2337/dc08-0545. Erratum in: Diabetes Care. 2009 Jan;32(1):207. PMID: 18540046; PMCID: PMC2742903.
- Millan-Ferro A, Garcia-Dolagaray G, Gautam S, Caballero AE, Mitri J. Impact of Monthly A1C Values Obtained at Home on Glycemic Control in Patients With Type 2 Diabetes: A Randomized Clinical Trial. Clin Diabetes. 2020 Jul;38(3):230-239. doi: 10.2337/cd19-0086. PMID: 32699471; PMCID: PMC7364448.
- Painter S, James R, Kompala T, Aguilar‐Shea A, Falcao M, Shah B. Estimated A1c is Highly Correlated with Home Kit A1c in a Large Remote Diabetes Monitoring Program. Diabetes Technology & Therapeutics. April 2022. A-1-A-237.
- The Peterson Health Technology Institute (PHTI); 2024. Accessed September 13, 2024. https://phti.org/assessment/digital-diabetes-management-tools/.
- Stratton IM, Adler AI, Neil HA, Matthews DR, Manley SE, Cull CA, Hadden D, Turner RC, Holman RR. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ. 2000 Aug 12;321(7258):405-12. doi: 10.1136/bmj.321.7258.405. PMID: 10938048; PMCID: PMC27454.
- Fitch K, Pyenson BS, Iwasaki K. Medical claim cost impact of improved diabetes control for medicare and commercially insured patients with type 2 diabetes. J Manag Care Pharm. 2013 Oct;19(8):609-20, 620a-620d. doi: 10.18553/jmcp.2013.19.8.609. PMID: 24074007; PMCID: PMC10437463.
- Turner RC, Cull CA, Frighi V, Holman RR. Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49). UK Prospective Diabetes Study (UKPDS) Group. JAMA. 1999 Jun 2;281(21):2005-12. doi: 10.1001/jama.281.21.2005. PMID: 10359389.
23Survodutide, a glucagon receptor/glucagon-like peptide-1 receptor (GCGR/GLP-1R) dual agonist, improves metabolic risk factors in adults living with obesity: analysis of a placebo-controlled, randomized phase 2 trial
Carel W. le Roux, Oren Steen, Kathryn J. Lucas, Elif I. Ekinci, Elena Startseva, Anna Unseld, Anita M. Hennige
St. Vincent’s University Hospital and University College Dublin School of Medicine, Dublin, Ireland;Private practice, Toronto, Ontario, Canada;Diabetes & Endocrinology Consultants PC, Morehead City, NC, USA;Austin Health, Heidelberg, Victoria, Australia;The Australian Centre for Accelerating Diabetes Innovation, University of Melbourne, Parkville, Australia;and Melbourne Medical School, University of Melbourne, Melbourne, Victoria, Australia;Boehringer Ingelheim International GmbH, Ingelheim, Germany;Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany;Boehringer Ingelheim International GmbH, Biberach, Germany
Purpose: Survodutide is a GCGR/GLP-1R dual agonist in clinical development for obesity. In a multinational phase 2 clinical trial in individuals with obesity without diabetes (NCT04667377), survodutide elicited up to 18.7% mean reduction in body weight after 46 weeks (the primary endpoint) according to actual treatment. We explored the effect of survodutide on metabolic parameters in this trial cohort.
Methods: In this randomized, double-blind, placebo-controlled phase 2 trial, 387 participants aged ≥18 to <75 years with body mass index (BMI) ≥27 kg/m² without diabetes were randomized 1:1:1:1:1 to once-weekly subcutaneous placebo or survodutide 0.6, 2.4, 3.6 or 4.8 mg for 46 weeks, comprising 20 weeks of dose escalation (when dose could also be adjusted for gastrointestinal [GI] tolerability) then 26 weeks’ maintenance. We evaluated changes in waist circumference and fasting plasma glucose (FPG) according to baseline glycated hemoglobin (HbA1c) levels (post hoc), as well as changes in disease stage according to the Edmonton Obesity Staging System (EOSS) and the Cardiometabolic Disease Staging (CMDS) system (pre-specified). We analyzed data descriptively for all participants receiving ≥1 dose of study drug with data for ≥1 efficacy endpoint, i.e. the full analysis set (FAS), according to doses received during the maintenance period (i.e. actual treatment) and those assigned at randomization (i.e. planned doses) using on-treatment data.
Results: In the FAS (n=384), baseline demographic and clinical characteristics were similar across treatment groups: overall mean age was 49.1 years, BMI 37.1 kg/m², and waist circumference 113.4 cm, while 262 (68.2%) were female, 301 (78.4%) white, 40 (10.4%) Asian and 37 (9.6%) black.
At baseline, 251 (65.4%) and 132 (34.4%) had HbA1c <5.7% (normoglycemia) and 5.7–6.5% (pre-diabetes), respectively. Survodutide was associated with reductions in waist circumference of up to 17.1 cm from baseline at week 46 by actual treatment, which were similar regardless of HbA1c level. Survodutide was also associated with reductions in FPG of up to 13.2 mg/dL (0.73 mmol/L) by actual treatment, which were numerically larger in participants with HbA1c 5.7–6.5% versus <5.7%. Reductions in waist circumference and FPG were similar when treatment groups were analyzed by planned doses. In general, individuals in the placebo group had lower stages of EOSS and CMDS at baseline, while more individuals in the survodutide groups shifted to lower stages at week 46. Overall, adverse events occurred in 90.9% and 75.3% of survodutide and placebo recipients, respectively (mainly GI: 75.1%, 41.6%). No survodutide recipients developed diabetes and more had HbA1c reduced from 5.7–6.5% to <5.7% versus placebo recipients;17 of 21 survodutide 4.8 mg recipients (81.0%) and 4 of 14 placebo recipients (28.6%).
Conclusions: In people with obesity, treatment with the GCGR/GLP-1R dual agonist survodutide was associated with clinically meaningful reductions in waist circumference and FPG in those with normoglycemia or pre-diabetes, as well as improvements in stage of obesity. *This is an encore abstract
Disclosures: CWLR has received personal fees from Boehringer Ingelheim, Eli Lilly, GI Dynamics, Gila Pharmaceuticals, Herbalife, Johnson & Johnson, Keyron, Novo Nordisk, and Zealand Pharma outside the submitted work. OS has received research support from Alnylam, Anji, AstraZeneca, Boehringer Ingelheim, CRISPR Therapeutics, Eli Lilly, Gilead Sciences, Janssen, Kowa, Medicago, Moderna, Novartis, Novo Nordisk, Pfizer, Sanofi, ViaCyte and Zucara Therapeutics;speaker bureau fees from Abbott, Amgen, AstraZeneca, Bausch Health, Boehringer Ingelheim, Eli Lilly, Janssen, LMC, Novo Nordisk and Sanofi;and consultancy fees from Amgen, Bayer, Eli Lilly, Novo Nordisk and Sanofi. KJL declares no conflicts of interest. EIE is a consultant to Bayer and Eli Lilly Australia, and her institute reports research funding support from Amgen, Bayer, Boehringer Ingelheim, Eli Lilly Australia, and Versanis. ES, AU, and AMH are employees of Boehringer Ingelheim.
This encore abstract was originally presented at the 31st European Congress on Obesity (Venice, Italy; May 12–14, 2024)
34Trends in the diagnostic landscape of metabolic dysfunction-associated steatohepatitis in a large real-world population
Semiu O. Gbadamosi1, Abdalla Aly1, Eniola Olatunji1, Aarth Sheth2, Andres Quintero3
- Real-World Evidence, Clinical Data Science and Evidence, Novo Nordisk Inc., Plainsboro, New Jersey, US;2. HEOR Evidence Strategy and Synthesis, Clinical Data Science and Evidence, Novo Nordisk Inc., Plainsboro, New Jersey, US;3. Medical Affairs, Novo Nordisk Inc., Plainsboro, New Jersey, US
Purpose: Metabolic dysfunction-associated steatohepatitis (MASH), formerly known as non-alcoholic steatohepatitis (NASH), is a growing health concern worldwide. Early diagnosis and disease management is essential to prevent disease progression. Among the many barriers to diagnosis, some key challenges include complex diagnostic pathways and between-specialty variation in clinical practice. To address these barriers, both the American Association for the Study of Liver Diseases (AASLD) and the American Association of Clinical Endocrinology (AACE) have issued clinical guidance for primary care physicians and specialists on the diagnosis and management of MASH. To assist with the early diagnosis of MASH, this analysis evaluated between-specialty variation in order to reveal insights into the diagnostic landscape of MASH. Using a large real-world cohort of patients with MASH, this study aimed to identify the physician specialties most and least frequently involved in the diagnosis of MASH and to examine trends in diagnosis by clinical specialties.
Methods: This study retrospectively analyzed administrative claims data from January 1, 2016 and December 31, 2023 from Komodo’s Healthcare Map™ in the USA. Adult patients who were newly diagnosed with MASH from 2018–2023 were eligible based on the following criteria: ICD-10 code K75.81 for NASH, patients with data on the provider type with ≥2 outpatient claims in the primary position ≤30 days apart or ≥1 inpatient medical claim in the primary position with a diagnosis of MASH. The first claim date was considered the date of MASH diagnosis by the physician. The index date was the first qualifying medical claim for MASH diagnosis. To reduce the likelihood of analyzing claims for clinically suspected MASH at the time of initial diagnosis, this study included a sensitivity analysis that involved indexing on the second outpatient claim associated with a MASH diagnosis. Data assessed from the index date included patient demographics, diagnosis date and diagnosing physician specialty. Diagnosing physician specialties were grouped: primary care (internal medicine and family medicine), liver specialists (hepatology and gastroenterology), and others (e.g., endocrinology, diagnostic radiology, oncology, and cardiology). To mitigate the risk of misclassifying previously diagnosed patients as newly diagnosed cases, a 24-month pre-index period/washout period was employed. Patients with any other liver disease ICD-10 diagnosis during the pre-index period were excluded. Data were summarized with descriptive statistics, including the frequency of MASH diagnosis by specialties for each year. To assess between-specialty variance in the diagnosis of MASH, longitudinal trends were evaluated with the Cochran-Armitage test.
Results: From a total of 714,265 patients with a diagnosis of MASH, patients meeting the pre-specified inclusion criteria amounted to a sample size of 99,313 for the study, from which 90,503 patients were included in the sensitivity analysis. Patients were predominantly female (55%), mostly between 45–64 years of age (58.2%). Highly prevalent comorbidities included lipid metabolism disorder (62.8%), hypertension (61.2%), o besity (55.9%), type 2 diabetes (42.5%), a combination of these (27.4%), or overweight (8.1%). The proportion of diagnosis by primary care physicians decreased from 61.3% in 2018 to 50.9% in 2023 (p<0.001). By contrast, the proportion of diagnoses made by liver specialists during this same period increased from 26.0% to 33.0% (p<0.001). A similar upward trend was observed for the remaining specialties, with an increase from 12.6% to 16.1% (p<0.001 ). In the sensitivity analysis, the longitudinal trend of MASH diagnosis by physician specialty over time decreased by a small albeit significant amount for primary care physicians from 61.3% to 59.5% (p<0.001), increased for other specialties from 13.1% to 14.0%;p<0.001), and did not vary significantly for liver specialists from 25.5% to 26.4% (p=0.329 ). Analyzing data across individual specialties from 2018 to 2023, a greater proportion of diagnoses were made by internal medicine practitioners (34.3% in 2018 to 28.7% in 2023;p<0.001), followed by family medicine practitioners (27.1% to 22.2%;p<0.001), and gastroenterologists (22.2% to 26.8%;p<0.001). Patients were less frequently diagnosed by specialists from hepatology, endocrinology, diagnostic radiology, oncology, cardiology, and other specialties (all <10%).
Conclusions: This study evaluated claims data on newly diagnosed patients with MASH between 2018 and 2023. Among patients with MASH, at least 50% of diagnoses were made by primary care physicians. Although higher than expected, this was not surprising, given that most patients with MASH have stage 0–2 fibrosis, which do not warrant referral to liver specialists for possible or suspected MASH diagnosis per specialty guidelines. This analysis demonstrates that over time, among patients with initial claims for MASH, the percentage of patients diagnosed by primary care physicians decreased while the percentage of patients diagnosed by liver specialists increased. One explanation for these observations may be if there was a change in the epidemiology of disease severity. For example, the distribution of stages of fibrosis could be changing towards more advanced fibrosis over time;in this case, patients with MASH may be more likely to be referred to liver specialists for diagnostic workups to monitor and assess disease progression. Nonetheless, these findings warrant further analysis through additional studies since this study did not evaluate fibrosis staging. These findings contribute to the understanding of MASH diagnosis among physicians in the USA, and could inform specialty-specific awareness, education, and strategies for better early detection of MASH and downstream management.
Disclosures: All authors are employees of Novo Nordisk Inc and hold shares in Novo Nordisk.
12VICTORION-INITIATE: Low-density Lipoprotein Cholesterol Goal Attainment with “Inclisiran First” versus Usual Care in Patients with Atherosclerotic Cardiovascular Disease
Rodriguez1, M. Koren2, C. East3, Y. Ali4, K. Kleeman4, S. Sarwat4, C. Abbas4, P.P. Toth5,6
- Division of Cardiovascular Medicine and the Center for Digital Health, Stanford University School of Medicine, Stanford, CA, USA; 2. Jacksonville Center for Clinical Research, Division of Flourish Research, Jacksonville, FL, USA; 3. Soltero Cardiovascular Research Center, Baylor Scott & White Research Institute, Dallas, TX, USA; 4. Novartis Pharmaceutical Corporation, East Hanover, NJ, USA; 5. Preventive Cardiology, CGH Medical Center, Rock Falls, IL, USA; 6. Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Purpose: Rapid and sustained attainment of guideline-recommended low-density lipoprotein cholesterol (LDL-C) goals is critical for patients with atherosclerotic cardiovascular disease (ASCVD). In VICTORION-INITIATE (NCT04929249), inclisiran administered twice yearly by a health care professional earlier in the treatment pathway allowed more patients with ASCVD to achieve and sustain LDL-C goals versus current usual care. This analysis aimed to evaluate average LDL-C exposure in the overall population and LDL-C goal attainment and safety in subgroups of patients (type of ASCVD, timing of ASCVD event, and history of statin intolerance) who received an “inclisiran first” implementation strategy (adding inclisiran immediately on failure to achieve LDL-C <70 mg/dL with maximally tolerated statins) compared with usual care.
Methods: VICTORION-INITIATE was a 330-day, prospective, pragmatically designed trial that randomized patients 1:1 (stratified by insurance status) to inclisiran first (open-label inclisiran 284 mg at Days 0, 90, and 270 plus usual care) or usual care alone (lipid management directed by treating physician’s discretion). The study took place at 45 sites across 20 states in the USA. Treating physicians had access to LDL-C measurements and were encouraged to intensify treatment per clinical practice guidelines. Average LDL-C exposure from Day 90 to Day 330 in the overall population was analyzed using a mixed-effects model for repeated measures, including treatment, visit, baseline, health insurance at baseline, treatment-by-visit interaction, and baseline-by-visit interaction as explanatory variables. Average least squares (LS) means of LDL-C values were estimated using linear contrasts of the model parameters. This prespecified subgroup analysis evaluated LDL-C goal attainment by timing of the most recent ASCVD event (<1 year/≥1 year prior to consent), ASCVD subtype (coronary heart disease [CHD], peripheral arterial disease [PAD], and cerebrovascular disease [CVD]), and statin intolerance status.
P values were obtained using a logistic regression model, including treatment, baseline LDL-C, and health insurance at baseline as explanatory variables by subgroup. Missing data were imputed using ‘non-responder’ (ie, ‘negative’ outcome) imputation. Safety by subgroup was also evaluated.
Results: Of 450 patients randomized to inclisiran first or usual care, 11.1% and 84.2% had an ASCVD event <1 year or ≥1 year prior to consent, respectively; 91.8%, 18.2%, and 14.7% of patients had a history of CHD, CVD, or PAD, and 25.8% were statin intolerant. The observed baseline mean LDL-C was 97.4 mg/dL in both treatment arms. Average exposure to LDL-C from Day 90 to Day 330 was significantly lower in patients treated with inclisiran first (n=223, LS mean: 42.4 [95% CI: 39.7, 45.1]) versus usual care (n=209, LS mean: 90.7 [95% CI: 87.9, 93.5]; LS mean difference: −48.3 [95% CI: −52.2, −44.4]; P<0.001). At Day 330, irrespective of subgroup, significantly more patients (P<0.001) who received inclisiran first achieved LDL-C goals of <70 mg/dL (inclisiran first: 63.9% to 91.7%, usual care: 13.3% to 34.6%) and <55 mg/dL (inclisiran first: 55.6% to 83.3%, usual care: 3.3% to 23.1%) versus usual care. Across subgroups, the incidence of treatment-emergent adverse events (TEAEs) and serious TEAEs were similar between inclisiran first and usual care (inclisiran first: 52.6% to 71.2%, usual care: 46.2% to 66.0% and inclisiran first: 10.7% to 28.3%, usual care: 11.4% to 22.2%, respectively).
Conclusions: Patients with ASCVD and LDL-C >70 mg/dL who received inclisiran first had lower average LDL-C exposure over the study period than those treated with usual care. Inclisiran first resulted in rapid and sustained achievement of LDL-C goals regardless of ASCVD subtype, event timing, and statin intolerance. The safety profile of inclisiran first was consistent across the subgroups analyzed.
Disclosures: FR has received consulting fees from Health Pals, Novartis, Novo Nordisk (CEC), Edwards, Kento Health, Inclusive Health, Arrowhead Pharmaceuticals, Movano Health, iRhythm, and HeartFlow; and has equity in Carta Healthcare. MJK is an employee of a company that received PI fees for his participation in the Novartis VICTORION-INITIATE trial and has received study grants and consulting fees from multiple manufacturers of PCSK9 inhibitors and other treatments for lipid disorders. CE has received research support from Amgen, Bard, 89bio, Gore, Lilly, Medtronic, Merit Medical, Mission Therapeutics, Novartis, Novo Nordisk, Penumbra, and Recor Medical. YA, KK, SS, and CAA are employees of Novartis Pharmaceuticals Corporation. PPT has received speaker bureau fees from Amgen; and has served as a consultant for Novartis.
5A Real-World Study of the Risk of Cardiovascular Events and Atherosclerosis among Patients with Severe Hypertriglyceridemia
Asia Sikora Kessler1, Kirti Batra2, Qiana Amos2, Damon Van Voorhis2, Seth Baum3, Daniel E. Soffer4, Montserrat Vera-Llonch1
1 Ionis Pharmaceuticals, Inc. Carlsbad, CA; 2 Optum, Eden Prairie, MN, 3 Flourish Research, Boca Raton, FL; 4 University of Pennsylvania Health System, Philadelphia, PA
Purpose: Elevated triglycerides (TG) are known to be a marker of cardiovascular risk. However, existing evidence on the association between the risk of cardiovascular events at distinct levels of elevated TG is limited. This real-world study evaluates the risk of cardiovascular (CV) events and atherosclerosis in patients with mild-to-moderate and severe TG levels compared to normal TG levels.
Methods: This retrospective cohort study was conducted using the Optum Research Database, which is a large US database that includes administrative claims and linked laboratory data for commercial and Medicare Advantage Part D health plan enrollees (observation period: 01 January 2016 – 31 March 2022). Adults 18 years and older with ≥1 diagnostic test for serum/plasma TG were included. Patients were assigned to one of four TG cohorts: normal TG (35≤TG<150 mg/dL), mild-to-moderate hypertriglyceridemia (HTG) [150≤TG<500 mg/dL], and severe hypertriglyceridemia (sHTG;divided into 500≤TG<880 mg/dL or TG≥880 mg/dL sub-cohorts). The index date was the cohort-specific earliest observed TG measurement. Patients had at least 12 months of pre- and post-index continuous enrollment. The primary study outcomes were CV events and atherosclerosis. CV events were a composite outcome defined as presence of at least one of the following: ≥1 claim for myocardial infarction not leading to death, ≥1 claim for unstable angina, acute coronary syndrome, stroke or transient ischemic attack, ≥1 claim for coronary or peripheral revascularization, and ≥1 claim for heart failure-specific hospitalization or emergency visit. Atherosclerosis was defined as presence of ≥1 claim with the diagnosis. Incidence rates were calculated per 100,000 person-years at risk. Kaplan-Meier analysis (for CV events and atherosclerosis) and a multivariate adjusted Cox proportional hazards model (for CV events only) were conducted to estimate cardiovascular risk in the mild-to-moderate HTG and sHTG cohorts compared with the normal TG cohort.
Results: A total of 134,316 patients were identified across the four cohorts. The mean (standard deviation, [SD]) age of all patients was 56.3 (15.7) years, 54% were males, and the mean (SD) follow-up was 987 (446) days.
Compared to the normal TG cohort, the mild-to-moderate HTG, the 500≤TG<880 mg/dL, and the TG≥880 mg/dL cohorts had significantly higher incidence rates of CV events (incidence rate ratio [IRR]: 1.4, 1.6, and 1.3 respectively;all p<0.001) and atherosclerosis (IRR: 1.6, 1.7, and 1.3 respectively;all p<0.001). The cumulative incidence of CV events at 3 years was 12.1% in the mild-to-moderate HTG cohort, 13.6% in the 500≤TG<880 mg/dL sub-cohort, and 11.4% in the TG≥880 mg/dL sub-cohort, compared to 8.8% in the normal TG cohort (p<0.001). The 3-year cumulative incidence of atherosclerosis was 24.0% in the mild-to-moderate HTG cohort, 25.6% in the 500≤TG<880 mg/dL sub-cohort, and 20.1% in the TG≥880 mg/dL sub-cohort, compared to 16.2% in the normal TG cohort (all p<0.001). The adjusted Cox regression model for CV events demonstrated a 17.0% higher risk in the 500≤TG<880 mg/dL sub-cohort (hazard ratio [HR] 1.17, 95% confidence interval [95% CI] 1.11-1.23) and a 21.0% higher risk in the TG≥880 mg/dL sub-cohort (HR 1.21, 95% CI 1.09 – 1.35), compared to the normal TG cohort. Other significant predictors of CV events included increased age, prior (baseline) history of CV events, presence of comorbidities associated with cardiovascular risk at baseline (i.e., hypertension, diabetes, and chronic kidney disease), total cholesterol ≥ 240 mg/dL, and a higher Charlson Comorbidity Index score.
Conclusions: Patients with elevated TG levels had higher risk of CV events and atherosclerosis compared to patients with normal levels, with further increased risk for patients with sHTG. This observation affirms the relationship between TG levels and CV disease, and demonstrates the need for improved therapeutic interventions for the clinical management of sHTG.
Disclosures: Asia Sikora Kessler is an employee of Ionis and owns company stock. Kirti Batra is an employee of Optum/UHG which was contracted to conduct this research. Qiana Amos is an employee of Optum/United Health Group (UHG) which was contracted to conduct this research. She is also a shareholder of UHG Stock. Damon Van Voorhis is an employee of Optum/UHG which was contracted to conduct this research. Seth Baum is an investigator and consultant for Ionis Pharmaceuticals. Daniel Soffer is an investigator and consultant for Ionis Pharmaceuticals;Consultant/Advisor – Akcea, Novartis, Amgen, Amryt/Chiesi, GeninCode, PHAR, Endless Health, New Amsterdam, Heartflow;Investigator – Amgen, Amryt/Chiesi, Novartis, Verve, PCORI, NIH, Heartflow, Regeneron, Lilly. Montserrat Vera-Llonch is an employee of Ionis and owns company stock.
9Assessment of unmet clinical needs and healthcare resource use among statin-treated patients with or at risk of developing ASCVD: A Claims-Based Retrospective Cohort Analysis
Andrew Hsieh, PharmD1; Jacqueline Shehata, PharmD1; Jeremy Smart, PharmD1; Timothy Llanos1; Brian Leinwand, PhD2; Ahan Ali2; Dushyant Katariya2; Nancy Ortiz, PharmD1
1 New Amsterdam Pharma, The Netherlands, 2 Trinity Life Sciences, Waltham, MA, USA
Purpose: Atherosclerotic cardiovascular disease (ASCVD) leads to considerable clinical and economic burdens. Primary prevention and secondary prevention of cardiac events seek to control low-density lipoprotein cholesterol (LDL-C) to established goals, which vary based on prevention setting and patient factors. Statins aim to lower LDL-C and are first-line treatment. Many patients struggle controlling LDL-C, despite use of statins, leading to poor health outcomes. The study objective was to estimate US unmet clinical needs, healthcare utilization and costs in primary and secondary prevention settings, based on LDL-C goal attainment.
Methods: This retrospective cohort study leveraged 2020-2021 MarketScan administrative claims linked to laboratory data, to assess the clinical and economic burden of statin-treated patients not at LDL-C goals. Patients taking statins were segmented into 6 groups based on the prevention setting, LDL-C goal attainment, and risk level (secondary prevention).
The number of statin treated patients in each segment was estimated and inflated to national estimates, along with annualized healthcare resource utilization and all-cause healthcare costs.
Results: Almost 125,000 statin treated patients did not meet LDL-C goals. The US national estimates suggest that 7.8 and 9.7 million patients in primary prevention were above and far above goal, respectively. In secondary prevention, 5 million and 8 million patients were above and far above goals. High healthcare utilization emerged in multiple settings of care (e.g., outpatient, inpatient, and emergency department) across prevention settings and risk levels. Mean annual costs for primary prevention above goal were approximately $9,000, while annualized costs for not high risk and very high-risk secondary prevention above goal were approximately $14,000 and $27,000, respectively.
Conclusions: Millions of patients on statins are not achieving their LDL-C goals, indicating a significant clinical burden among patients with, or at risk for ASCVD. This unmet treatment need results in substantial healthcare resource use and costs each year.
Disclosures: Nothing to disclose by any author(s)
31Cardiovascular and cerebrovascular event-related mortality in the African Americans;a twenty-year time-trend analysis.
Shaaf Ahmad(1), Uzair Nisar Malik(2), Kaleem Maqsood(3), Muhammad Amir(3)
- University of North Carolina at Chapel Hill, 2. King Edward Medical University 3. The University of the Punjab
Purpose: To determine the impact of targeted healthcare interventions aimed at improving cardiovascular and cerebrovascular disease outcomes among the African American populations, by recording a longitudinal trend shift over the course of the last two decades.
Methods: The CDC WONDER database was queried from 1999-2020. Only the patients identifying as African-Americans were deemed eligible for inclusion. Age-adjusted mortality rates (AAMR) per 100,000 with 95% confidence intervals were obtained. Log-linear regression model was fitted for estimating trend shift with annual percent change (APC) and average annual percent change (AAPC) values. Joinpoint® 5.2.0 statistical package was used for computation. A p-value of >0.05 was considered significant.
Results: A total of 1,532,522 deaths attributable to ischemic heart disease (62%), congestive heart failure (9.3%), hypertensive heart failure (11.2%), and stroke (17.3%) were recorded among the African Americans over the duration of the study period.
The overall incidence in mortality due to ischemic heart disease (AAMR1999: 226.6 to AAMR2020: 114.4, AAPC1999-2020: -3.3, 95% CI: -3.5, -3.0) and stroke (AAMR1999: 62.4 to AAMR2020: 32.3, AAPC1999-2020: -3.3, 95% CI: -3.5, -3.1) decreased in the past two decades. While the AAMR for congestive heart failure and hypertensive heart disease experienced an upturn in the later half of the study period (AAPC-congestive heart failure: 0.8, 95% CI: 0.6, 0.9 and AAPC-HHD= 1.0 95% CI: 0.5, 1.4).
Conclusions: The results of our analysis reveal a positive trend of improvement in the ischemic heart disease and stroke related mortality among the African American populations. However, an increase in hypertensive and congestive heart disease related mortality following a period of stability is alarming and calls for immediate remediation. Strategies developed by taking into account the socioeconomic and historical determinants, such as poverty, an underrepresentation and general mistrust of the healthcare system, and a lack of education among other factors associated with worse outcomes in this subgroup are the need of the hour.
Disclosures: Nothing to disclose by any author(s)
2Contemporary Prevalence, Comorbidity Burden, and Treatment of Overweight and Obesity: Insights from the Multicenter Mass General Brigham Healthcare System
John W. Ostrominski, MD1,2,3;David Zelle, BA1;Ozan Unlu, MD1,3;Austen M. Smith, DO2,3;Michela Tucci, MPH1;Heather J. Baer, ScD3,4,5;Christopher P. Cannon, MD1,3;Caroline M. Apovian, MD2,3;Joshua Toliver, PhD6;Wojciech Michalak, MSc6;Anthony Fabricatore, PhD6;Briain O. Hartaigh, PhD6;Benjamin M. Scirica MD MPH1,3;Kelly Olsson, MA6;Alexander J. Blood, MD, MSc1,2,3
1: Division of Cardiovascular Medicine, Brigham and Women’s Hospital, Boston, MA, USA;2: Division of Endocrinology, Diabetes and Hypertension, Brigham and Women’s Hospital, Boston, MA, USA;3: Harvard Medical School, Boston, MA, USA;4: Division of General Internal Medicine and Primary Care, Brigham and Women’s Hospital, Boston, MA USA;5: Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA;6: Novo Nordisk Inc., Plainsboro, NJ USA
Purpose: Real-world evidence is critical to identify treatment gaps and inform healthcare service design, but contemporary anti-obesity medication (AOM) use patterns are sparsely reported. The aim of this analysis was to describe the prevalence of obesity/overweight, evidence-based obesity-related conditions (ORCs), and AOM use among eligible patients, with a focus on cardiovascular disease (CVD).
Methods: In this cross-sectional analysis of the multicenter Mass General Brigham healthcare system spanning 2018-2022, we identified all adult patients eligible for AOM (BMI 27-29.9 kg/m2 with ≥1 ORC or BMI ≥30 kg/m2). The prevalence of ORCs was ascertained using administrative codes and available EHR data. Prescription of FDA-approved AOM by BMI category, number of ORCs, number of key CVD risk factors, and the presence of prior MACE were also evaluated.
Results: Of 2,469,474 individuals who met inclusion criteria, 1,110,251 (45%) were eligible for AOM (median age, 54 years;57% female). Of these, 31%, 41%, 17%, and 11% had a BMI (kg/m2) of 27-29.9, 30-34.9, 35-39.9, and ≥40, respectively. Prior metabolic/bariatric surgery was seen in 1%. Musculoskeletal disorders (53%), dyslipidemia/hyperlipidemia (37%), and hypertension (35%) were the most common ORCs, with ≥2 ORCs observed in 62%. Prescription of any FDA-approved AOM was observed in only 1.4% of all eligible patients. Liraglutide 3.0 mg (46% of all AOM) was the most prescribed AOM.
AOM prescriptions increased modestly with higher BMI, ORC burden, and number of CVD risk factors. Among those with prior MACE (9%), 1% (also 1% if without T2DM) were prescribed FDA-approved AOM.
Conclusions: Although nearly 1 in 2 contemporary patients in a large healthcare system are eligible by guidelines and FDA labeling, AOM prescription remains exceedingly low, even among high-risk persons with severe obesity and established CVD. Novel care delivery pathways are needed to accelerate closure of these considerable implementation gaps.
Disclosures: Heather J. Baer: Research grants- PCORI (Patient-Centered Outcomes Research Institute) and NIH (National Institutes of Health);Consulting- American University of Beirut (for SHARP, Scholars in Health Research Program) Christopher P. Cannon: Research Grants- Amgen, Better Therapeutics, Boehringer Ingelheim, Daiichi Sankyo, Merck, Novo Nordisk, Pfizer;Consulting- Amryt/Chiesi, Alnylam, Amarin, Amgen, Applied Therapeutics, Ascendia, Biogen, Boehringer Ingelheim, Bristol Myers-Squibb, CSL Behring, Eli Lilly, Janssen, Lexicon, Merck, Milestone, Pfizer, Rhoshan, Sanofi Caroline M. Apovian: Research Grants- NIH, PCORI and GI Dynamics, Inc.;Advisory Board Participation- Altimmune, Inc., CinFina Pharma, Inc., Cowen and Company, LLC, Currax Pharmaceuticals, LLC, EPG Communication Holdings Ltd, Form Health, Inc., Gelesis, Srl., L-Nutra, Inc., NeuroBo Pharmaceuticals, Inc., Novo Nordisk, Inc., OptumRx, Inc., Pain Script Corporation, Palatin Technologies, Inc., Pursuit By You, ReShape Lifesciences Inc., Riverview School, Xeno Biosciences Joshua Toliver, Wojciech Michalak, Anthony Fabricatore, Briain O. Hartaigh, Kelly Olsson: Employees of, and shareholders in, Novo Nordisk, Inc. Benjamin M. Scirica: Research Grants- Better Therapeutics, Boehringer Ingelheim, Merck, NovoNordisk, and Pfizer;Consulting- Abbvie (DSMB), AstraZeneca (DSMB), Boehringer Ingelheim, Better Therapeutics, Bristol Myers-Squibb, Elsevier Practice Update Cardiology, Esperion, Hanmi (DSMB), Lexeo (DSMB), Lexicon, NovoNordisk;Equity- Health [at] Scale and Doximity. Alexander J. Blood: Research Grants- Boehringer Ingelheim, Novo Nordisk, Eli Lilly, General Electric Health;Consulting- Walgreens Health, Color Health, Arsenal Capital Partners;Equity- Knownwell
36Effect of IL-6 Inhibition on Lipoprotein(a) Levels: A Systematic Review and Meta-Analysis
Saeid Mirzai, Emil deGoma, John Walsh, Raya Mahbuba, Yung Chyung, Michael D. Shapiro
Wake Forest University School of Medicine, Tourmaline Bio, Inc.
Purpose: Phase 3 trials are currently evaluating anti-IL-6 monoclonal antibodies (mAbs) in atherosclerotic cardiovascular disease (ASCVD). Experimental studies suggest that IL-6 inhibition may reduce ASCVD risk via mechanisms like reducing endothelial activation, leukocyte recruitment, foam cell formation, plaque rupture, and hepatic synthesis of prothrombotic proteins. Importantly, IL-6 inhibition may decrease hepatic apolipoprotein(a) [apo(a)] synthesis, lowering lipoprotein(a) [Lp(a)], a highly atherogenic lipoprotein. We conducted a systematic review and meta-analysis to quantify the effect of anti-IL-6/IL-6R mAbs on Lp(a) levels.
Methods: We searched PubMed, EMBASE, and Cochrane databases for studies published by June 30, 2024, that reported pre- and post-treatment Lp(a) levels and absolute Lp(a) changes and compared repeat doses of anti-IL-6/IL-6R mAbs versus a comparator (i.e., tumor necrosis factor inhibitors or placebo) over time. Given variability in reported units, the standardized mean difference (SMD) in Lp(a) levels was calculated using a random-effects model, accounting for heterogeneity. Medians/interquartile ranges were converted to means/standard deviations (SDs) using the methods described by Wan et al. (2014). Missing absolute change SDs were calculated using Cochrane methods.
Results: The analyses included ten studies with 1,201 total participants (876 rheumatoid arthritis, 325 chronic kidney disease) receiving either an anti-IL-6/IL-6R mAb (311 tocilizumab, 153 sarilumab, 247 ziltivekimab) or comparator (78 placebo, 412 TNFi). The mean age across the study groups ranged from 50 to 70 years, with 25 to 100% women. The follow-up duration ranged from 2 to 12 months. The average Lp(a) levels across all studies and treatment groups were 65.7 (SD 89.5) nmol/L among 325 participants and 25.7 (SD 32.8) mg/dL among 876 participants.
Eight studies (n=648) provided the data necessary to compare pre- to post-treatment Lp(a) levels at 2-3 months following anti-IL-6/IL-6R mAb therapy. Pooled analysis indicated a reduction in Lp(a) at 2-3 months with SMD of -0.29 (95% CI -0.44 to -0.14). There were four studies (n=243) that had 6-month follow-up data. Pooled analysis indicated a reduction in Lp(a) at 6 months with SMD of -0.33 (95% CI -0.51 to -0.15, p<0.001). Four comparative studies that had 2-3 month follow-up data were pooled (n=915) for a total of 534 participants receiving anti-IL-6/IL-6R mAb therapy compared with 381 participants receiving the comparator. Pooled analysis indicated a reduction in Lp(a) at 2-3 months with an SMD of -0.49 (95% CI -0.73 to -0.24, p<0.001). There were two comparative studies that had 6-month follow-up data (n=450) which were pooled for a total of 200 participants receiving anti-IL-6/IL-6R mAb therapy compared with 250 participants receiving the comparator. Pooled analysis indicated a reduction in Lp(a) at 6 months with SMD of -0.97 (95% CI -1.16 to -0.77, p<0.001).
Conclusions: This meta-analysis indicates significant reductions in Lp(a) levels with anti-IL-6/IL-6R mAbs compared to controls. The potential clinical relevance for ASCVD prevention warrants further investigation in outcome trials.
Disclosures: SM has no interests to disclose. EdG, JW, and YC are employees of Tourmaline Bio, Inc. RM declares no conflicts of interest. MDS is supported by institutional grants from Amgen, Arrowhead, Boehringer Ingelheim, 89Bio, Esperion, Novartis, Ionis, Merck, New Amsterdam, and Cleerly;has participated in scientific advisory boards with Amgen, Agepha, Ionis, Novartis, New Amsterdam, and Merck;and has served as a consultant for Ionis, Novartis, Regeneron, Aidoc, Shanghai Pharma Biotherapeutics, Kaneka, Novo Nordisk, Arrowhead, and Tourmaline.
4Extensive Atherosclerotic Coronary Artery Disease in a Patient with Severe Hypertriglyceridemia
Asem Ali, Khanh-Van Tran
Boston University Medical Center, UMass Memorial Medical Center
Purpose: Although severe hypertriglyceridemia is a known risk factor for acute pancreatitis, it can also be associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD) in certain patient groups. Unfortunately, cardiovascular evaluation is sometimes overlooked, putting patients at risk for significant cardiac events. We present a case of a patient with severe hypertriglyceridemia found to have extensive coronary artery disease (CAD)
Methods: A 41-year-old male with a past medical history of Type 2 diabetes mellitus, hypertension, a previous episode of hypertriglyceridemia-induced pancreatitis while on liraglutide, and transverse sinus stenosis was admitted to the hospital for management of hypertriglyceridemia. His home medications included insulin glargine, metformin, carvedilol, lisinopril, rosuvastatin, ezetimibe, fenofibrate, and icosapent ethyl. His diabetes was poorly controlled at that time. His triglyceride levels were 7,026 mg/dL. Though he had no evidence of pancreatitis, he was placed on IV insulin for management for prevention of pancreatitis. During the admission, his history revealed that his mother had passed away at age 53 from coronary artery disease, yet he had not previously been evaluated for CAD. He was initiated on a PCSK9 inhibitor and referred to cardiology for outpatient evaluation.
His triglycerides levels improved to less than 500. During outpatient cardiology evaluation, the patient was referred for cardiac catheterization, which revealed right-dominant circulation with three-vessel CAD, including a 100% chronic occlusion of the proximal left anterior descending artery (LAD), 50% narrowing of the ramus intermedius, and non-hemodynamically significant stenoses in the right coronary artery (RCA) and left circumflex artery (LCx). The patient underwent successful percutaneous coronary intervention (PCI) of the proximal LAD with full restoration of TIMI 3 flow.
Results: This case provides a valuable reminder to clinicians to consider cardiac risk evaluation and management in patients with severe hypertriglyceridemia, and not only for pancreatitis risk. In this instance, the patient, with a significant family history of CAD, was not evaluated, likely due to his young age and the common misconception that severe hypertriglyceridemia only increases the risk of pancreatitis. Given the extent of his disease, the outcomes could have been devastating.
Conclusions: It is of utmost importance to give attention to cardiac risk factors should be considered in all patients with hypertriglyceridemia, regardless of the severity.
Disclosures: Nothing to disclose by any authors.
13Knowledge gap and prescribing patterns of GLP-1RA and SGLT2 inhibitors among Chinese doctors: findings from Cardio-Metabolic Survey
Jing Liu1, Xiaofeng Su1, Yongchen Hao2, Jing Liu2, on behalf of CMS investigators
- Peking University People’s Hospital; 2. Beijing Anzhen Hospital, Capital Medical University
Purpose: New anti-diabetic medications, such as glucagon like peptide 1 receptor agonists (GLP-1RA) and sodium glucose co-transporter 2 (SGLT2) inhibitors are recommended to reduce cardiovascular and renal events in type 2 diabetes mellitus (T2DM) by recent guidelines, independent of glucose control. While there is still room for improvement in their clinical utilization in real world. This study aims to address the knowledge gap, prescription patterns and willingness, and barriers faced by Chinese doctors.
Methods: The Cardio-Metabolic Survey (CMS) was a cross-sectional study conducted among doctors across Beijing who managed diabetic patients in clinical practice, via an online survey platform, Surveystar, from May 1st, to Dec. 31th, 2022.
Results: A total of 358 doctors from 57 hospitals across Beijing participated in this survey, 34.9% were from tertiary hospitals and the other from secondary hospitals or community healthcare centers.
Only 30%-40% doctors demonstrated a somewhat understanding of the mechanism and clinical applications of GLP-1RA or SGLT2 inhibitors. There is no significant difference in the level of understanding of these two medications overall (p = 0.336). However, the doctors in tertiary hospitals have a higher understanding of GLP1-RA and SGLT2 inhibitors compared to those in non-tertiary hospitals (understanding of GLP1-RA: Pearson’s R = 0.104, p = 0.049, understanding of SGLT2 inhibitors: Pearson’s R = 0.139, p = 0.008). 40.2% of doctors have never prescribed GLP1-RA, and 36.6% for SGLT2 inhibitors. The frequency of prescribing SGLT2 inhibitors was significantly higher than prescribing GLP-1RA (p = 0.005). The main barriers for clinicians in prescribing GLP-1RA or SGLT2 inhibitor include high cost, poor adherence, concerns about side effects, and insufficient knowledge about these medications.
Conclusions: Limited understanding and low prescription frequency for GLP-1RA and SGLT2 inhibitors were found in Chinese doctors. Prescription barriers include high costs and limited knowledge. Enhancing doctors’ understanding of GLP-1RA and SGLT2 inhibitors and strengthening the ability for T2DM management, are urgently needed.
Disclosures: Nothing to disclose by any authors.
27Lipid goal attainment across baseline socioeconomic and clinical factors comparing an “inclisiran first” implementation strategy and usual care: Subgroup analysis of VICTORION-INITIATE
Koren1, F. Rodriguez2, P.P. Toth3,4, Y. Ali5, K. Kleeman5, S. Sarwat5, C. Abbas5, C. East6
- Jacksonville Center for Clinical Research, Division of Flourish Research, Jacksonville, FL, USA; 2. Division of Cardiovascular Medicine and the Center for Digital Health, Stanford University School of Medicine, Stanford, CA, USA; 3. Preventive Cardiology, CGH Medical Center, Rock Falls, IL, USA; 4. Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD, USA; 5. Novartis Pharmaceutical Corporation, East Hanover, NJ, USA; 6. Soltero Cardiovascular Research Center, Baylor Scott & White Research Institute, Dallas, TX, USA.
Purpose: Addressing inequities in cardiovascular care has become a public health priority. Recent results from VICTORION-INITIATE (NCT04929249), a pragmatically designed, randomized clinical trial, showed the benefit of using inclisiran immediately if patients with atherosclerotic cardiovascular disease (ASCVD) failed to achieve low-density lipoprotein cholesterol (LDL-C) <70 mg/dL on maximally tolerated statins. This analysis aimed to evaluate the effectiveness and safety of an “inclisiran first” implementation strategy versus usual care in subgroups that may be associated with health care inequities.
Methods: VICTORION-INITIATE was conducted at 45 representative clinical settings across 20 states in the USA. Patients with ASCVD randomized 1:1 (stratified by insurance status) received open-label inclisiran 284 mg at Days 0, 90, and 270 plus usual care or usual care alone (lipid management directed by treating physicians). Treating physicians had access to LDL-C measurements and were encouraged to intensify treatment per lipid guidelines. We compared the efficacy and safety endpoints for inclisiran first and usual care in prespecified subgroups (race, ethnicity, sex, renal function, and statin intensity) and by income level (post-hoc analysis). LDL-C goal attainment was analyzed by subgroup using a logistic regression model with treatment, baseline LDL-C, and health insurance at baseline as explanatory variables. Missing data were imputed using ‘non-responder’ (ie, ‘negative’ outcome) imputation. For percentage change from baseline to Day 330 in other lipids and lipoproteins, data were analyzed using a mixed-effects model for repeated measures with treatment, visit, baseline, health insurance at baseline, treatment-by-visit interaction, and baseline-by-visit interaction as explanatory variables assuming an unstructured covariance matrix.
Results: The study randomized 450 patients. Baseline demographic and clinical parameters were balanced between study arms (≥65 years of age: inclisiran first: 63.1%, usual care: 61.3%; non-White: inclisiran first: 15.6%, usual care: 15.1%;
Hispanic: inclisiran first: 13.8%, usual care: 16.9%; female: inclisiran first: 29.8%, usual care: 32.0%; income ≤$50,000: inclisiran first: 58.7%, usual care: 58.2%; estimated glomerular filtration rate ≥30 to <60 mL/min/1.73m2: inclisiran first: 20.0%, usual care: 17.8%; no statins at baseline: inclisiran first: 9.8%, usual care: 10.2%). At Day 330 across all subgroups, compared with usual care, significantly more patients in the inclisiran first arm achieved LDL C <70 mg/dL (inclisiran first: 50.0% to 91.1%, usual care: 8.8% to 25.4%; P<0.001 except for ‘statin intensity: none’ where P=0.005) and LDL-C <55 mg/dL (inclisiran first: 27.3% to 77.0%, usual care: 2.6% to 10.3%; P<0.001 except for ‘statin intensity: none’ where P=0.044). Within the usual care arm, the proportions of patients achieving LDL-C <70 mg/dL and <55 mg/dL, respectively, were numerically lower for non-White (8.8% and 2.9%) and Hispanic (10.5% and 2.6%) than White (24.6% and 10.2%) and non-Hispanic (24.9% and 10.3%) patients. We did not observe differences in LDL-C goal attainment for these subgroups in patients receiving inclisiran first. Compared with usual care, inclisiran first resulted in greater mean percentage change from baseline to Day 330 in non–HDL-C (least squares [LS] mean difference: −52.0% to −26.6%), apolipoprotein B (LS mean difference: −51.2% to −23.1%), and lipoprotein(a) (LS mean difference: −27.9% to −2.3%), irrespective of subgroup. The incidence of treatment-emergent adverse events (TEAEs) and serious TEAEs compared similarly between inclisiran first and usual care for each subgroup (inclisiran first: 35.5% to 69.2%, usual care: 34.2% to 84.2%, and inclisiran first: 3.2% to 16.9%, usual care: 0.0% to 36.8%, respectively).
Conclusions: VICTORION-INITIATE enrolled a diverse population reflective of “real-world” US clinical practice. The inclisiran first strategy consistently resulted in higher rates of LDL-C goal attainment for all subgroups studied and did not lead to differences in lipid outcomes by race or ethnicity as compared with usual care. No additional safety concerns for the inclisiran first strategy were identified.
Disclosures: MJK is an employee of a company that received PI fees for his participation in the Novartis VICTORION-INITIATE trial and that has received study grants and consulting fees from multiple manufacturers of PCSK9 inhibitors and other treatments for lipid disorders. FR has received consulting fees from HealthPals, Novartis, Novo Nordisk (CEC), Edwards, Kento Health, Inclusive Health, Arrowhead Pharmaceuticals, Movano Health, iRhythm, and HeartFlow; and has equity in Carta Healthcare. PPT has received speaker bureau fees from Amgen and has served as a consultant for Novartis. YA, KK, SS, and CAA are employees of Novartis Pharmaceuticals Corporation. CE has received research support from Amgen, Bard, 89bio, Gore, Lilly, Medtronic, Merit Medical, Mission Therapeutics, Novartis, Novo Nordisk, Penumbra, and ReCor Medical.
17Modeling the Impact of Semaglutide 2.4 mg in US Patients with Atherosclerotic Cardiovascular Disease and BMI ≥27 kg/m2
Mads Faurby, MSc1; Michael G. Nanna, MD2; Joshua C. Toliver, PhD, PharmD2; Quan V. Doan, PharmD3; Alasdair D. Henry, PhD3; Thomas Scassellati Sforzolini, MS3; Alina Levine, MS3; Anthony Fabricatore, PhD2, Azadeh S. Houshmand-Øregaard, MD, PhD2; Regan Sevinsky, PharmD, BCPS1; Ann Marie Navar, MD, PhD4
1 Novo Nordisk Inc., Plainsboro, NJ; 2 Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, CT; 3 Genesis Research Group, Hoboken, NJ; 4 UT Southwestern Medical Center, Dallas, TX
Purpose: The SELECT trial demonstrated a 20% risk reduction in major adverse cardiovascular events (MACE) with semaglutide 2.4 mg in adults with atherosclerotic cardiovascular disease (ASCVD) and overweight/obesity (BMI ≥27 kg/m2). We aimed to quantify the potential population impact of this treatment in the US.
Methods: National Health and Examination Survey (NHANES) data were used to characterize the US population meeting SELECT trial criteria: BMI ≥27 kg/m2, age ≥45 years, ASCVD, and no diabetes, with the number of potential treatment candidates determined using 2023 census projections. The 10-year rate of recurrent MACE events was estimated based on the SMART2 risk calculator. The potential treatment effect of semaglutide 2.4 mg on the number of MACE events in this population was estimated using results from the SELECT trial.
Results: As of 2023, 6,161,981 US adults met SELECT inclusion criteria (mean age 67.2 ± 9.9 years, 43.6% female, mean BMI 32.6 ± 5.0 kg/m2).
Based on SMART2, an estimated 2,529,310 individuals (41.0%) will experience at least one MACE event in the next 10 years, with the total number of events estimated at 3,064,993. Of these, 497,631 MACE events could be avoided with semaglutide 2.4 mg treatment.
Conclusions: The possible therapeutic impact of semaglutide 2.4 mg on eligible US adults is substantial, with the potential to prevent nearly half a million CV events and deaths over the next 10 years.
Disclosures: This research was funded by Novo Nordisk Inc. (Plainsboro, NJ, USA). Medical writing and editorial support was provided by Rebecca Hahn, MPH, of KJT Group, Inc. (Rochester, NY, USA), which was funded by Novo Nordisk Inc. MGN is a consultant for Merck and HeartFlow, Inc. He reports current research support from the American College of Cardiology Foundation supported by the George F. and Ann Harris Bellows Foundation, the Patient-Centered Outcomes Research Institute (PCORI), the Yale Claude D. Pepper Older Americans Independence Center (P30AG021342), and the National Institute on Aging/National Institutes of Health from R03AG074067. AMN reports funding for research to her institution from Esperion and Amgen, and honoraria and consulting fees from Amgen, Eli Lilly, Esperion, Janssen, Merck, NewAmsterdam, Novo Nordisk, Novartis, Pfizer, and Silence Therapeutics. Her spouse receives research funding to his institution from Amgen and Esperion, and consulting from Janssen and Amgen. MF, JT, AF, RS, AHØ are employees and shareholders of Novo Nordisk Inc. QVD, AH, TSS, AL are employed by Genesis Research Group, a consulting company that received funding from Novo Nordisk to carry out this research.
7Obicetrapib Demonstrates Significant Reductions of Lp(a) on Top of High-Intensity Statins
SotirosTsimikas1, Xiaohong Yang1, Andrew Hsieh2, Doug Fissel2, Marc Ditmarsch2, Michael Davidson2, John Kastelein2
1University of California San Diego, San Diego, United States of America, 2NewAmsterdam Pharma, Naarden, Netherlands
Purpose: Elevated lipoprotein (a) [Lp(a)] leads to increased cardiovascular disease (CVD) risk. There are no pharmacologic therapies approved for reducing Lp(a). Previous cholesteryl ester transfer protein (CETP) inhibitors and approved lipid agents have modest Lp(a) effects. We examined the effects of obicetrapib, a novel CETP inhibitor, on Lp(a).
Methods: ROSE1 and ROSE2 are phase 2 trials of obicetrapib on top of high-intensity statins by persons without CVD and low-density lipoprotein cholesterol >70 mg/dL. In ROSE1 120 subjects received 5 or 10 mg obicetrapib or placebo;in ROSE2 119 received 10 mg obicetrapib, 10 mg obicetrapib + 10 mg ezetimibe or placebo. Lp(a) was measured by immunoturbidimetry in ROSE1 and by the UCSD isoform independent assay using monoclonal antibody LPA-KIV9 in ROSE2.
Results: Median baseline Lp(a) for 10 mg obicetrapib and placebo was 29.9 and 45.3 nmol/L in ROSE1 and 44.0 and 37.8 nmol/L in ROSE2, respectively. Median % changes from baseline for obicetrapib 10 mg and placebo, respectively, were -56.5 and +4.00 in ROSE1 and -47.2 and +2.3 in ROSE2. Pooled (N=127) median difference in % change corrected for placebo was 57.1% (p<0.001). In both trials >50% of obicetrapib subjects had a >60% reduction in Lp(a).
Conclusions: Obicetrapib 10 mg on top of high-intensity statin significantly lowered Lp(a) by 57% vs. placebo in a pooled analysis, a substantially greater reduction than with proprotein convertase subtilisin kexin type 9 inhibitors (15-30%), niacin (30%) or other CETP inhibitors (25%).
Disclosures: This investigation was funded by NewAmsterdam Pharma, Naarden, The Netherlands
19Rates of Acute Pancreatitis and Cardiovascular Events among Adults with Severe Hypertriglyceridemia in US Clinical Practice
Seth J. Baum1, Asia Sikora Kessler2, Emily Kutrieb3, Montserrat Vera Llonch2, Alex Lonshteyn3, Derek Weycker3, Daniel E. Soffer4
1 Flourish Research, Boca Raton, FL, USA; 2 Ionis Pharmaceuticals Inc., Boston, MA, USA; 3 Avalere Health, Boston, MA, USA; 4 University of Pennsylvania Health System, Philadelphia, PA, USA
Purpose: Elevated triglycerides (TG) are an important risk factor for acute pancreatitis (AP) and cardiovascular (CV) events. The objective of this study was to estimate rates of AP and CV events within subgroups of adults defined by TG level—including those with severe hypertriglyceridemia (sHTG [TG ≥500 mg/dL])—in US clinical practice.
Methods: A retrospective observational cohort design and data spanning January 2013 through December 2019 from the Merative MarketScan Research Databases (Commercial Claims and Encounters, Medicare Supplemental and Coordination of Benefits, and Labs) were employed. The study population comprised adults with ≥1 TG value and was stratified based on the first observed TG value (<150 [normal], 150-499, 500-879, ≥880 mg/dL); adults without continuous healthcare enrollment during the 1-year period prior to the first TG value (“history period”) were excluded. AP and CV events were identified via hospitalizations with a corresponding principal diagnosis code and were ascertained from the first observed TG value through the end of the study period. CV events included hospitalizations for heart disease (e.g., myocardial infarction, unstable angina), cerebrovascular disease (e.g., stroke, transient ischemic attack [TIA]), and heart failure. Rates of AP and CV events per 1,000 person-years (PY) were estimated for each TG-specific subgroup, overall and for subsets defined therein based on age (<40, ≥40 years), pre-existing diabetes, history of AP, history of CV event, and history of lipid-lowering therapy, respectively.
Results: Study population totaled 1.8M adults (TG <150: N=1.3M; TG 150-499: N=449K; TG 500-879: N=12,050; TG ≥880: N=3,944). Selected baseline characteristics of the study population (ranges, across TG levels) were: age ≥40 years (71.1% [<150] to 81.3% [500-879]); male (40.9% [<150] to 73.8% [500-879]); pre-existing diabetes (12.9% [<150] to 39.1% [≥880]); history of AP (0.2% [<150] to 2.2% [≥880]); history of CV events (0.5% [<150] to 0.7% [≥880]); and history of lipid-lowering therapy (16.2% [<150] to 33.1% [≥880]).
On an overall basis, rates (95% confidence intervals) of AP per 1,000 PY increased monotonically from lowest TG value (<150: 0.6 [0.5-0.6]) to highest TG value (≥880: 9.9 [7.6-12.9]), corresponding to a relative rate of 17.4 (13.3-22.8) for adults with TG ≥880 versus TG <150. AP rates were particularly high among adults in the TG ≥880 subgroup who also had a history of AP (193.0 [127.3-292.8]), pre-existing diabetes (13.9 [10.2-19.0]), or a history of lipid-lowering therapy (13.9 [9.4-20.6]), or who were aged <40 years (17.0 [10.9-26.5]). Rates of CV events per 1,000 PY—on an overall basis— also increased monotonically from lowest TG value (<150: 3.3 [3.3-3.4]) to highest TG value (≥880: 10.3 [8.3-12.8]), corresponding to a relative rate of 3.1 (2.5-3.8) for adults with TG ≥880 versus TG <150. CV event rates were highest among adults in the TG ≥880 subgroup who also had a history of CV events (116.5 [61.6-220.5]), pre-existing diabetes (18.1 [14.0-23.4]), or a history of lipid-lowering therapy (14.5 [10.6-19.7]).
Conclusions: Rates of AP and CV events are substantially higher among adults with elevated TG values, and are especially high among adults with sHTG, in particular those with sHTG who also have other risk factors (or proxies for risk factors). Understanding the magnitude of disease risk among sHTG patients, with increasing levels of TGs as well as within important subgroups, is critical to improving patient care and outcomes.
Disclosures: Funding for this research was provided by Ionis Pharmaceuticals. Seth J. Baum is an investigator and consultant for Ionis Pharmaceuticals. Asia Sikora Kessler is an employee of Ionis Pharmaceuticals and owns company stock. Emily Kutrieb was employed by Avalere Health (during conduct of study), which received funding for this research from Ionis Pharmaceuticals. Montserrat Vera-Llonch is an employee of Ionis Pharmaceuticals and owns company stock. Alex Lonshteyn is employed by Avalere Health, which received funding for this research from Ionis Pharmaceuticals. Daniel E. Soffer is an investigator and consultant for Ionis Pharmaceuticals. Derek Weycker is employed by Avalere Health, which received funding for this research from Ionis Pharmaceuticals.
33Resolvin E1 heals injured cardiomyocytes: Therapeutic implications and H-FABP as a readout for cardiovascular disease & systemic inflammation
Allyson Zheng 1, Nasi Huang 2, David Bean 2, Sindhu Rayapaneni 1, Jude T. Deeney 2, Manish Sagar 3, James A. Hamilton 2
Boston University1, Boston University School of Medicine2, Boston Medical Center3
Purpose: Acute coronary syndrome (ACS) is the leading cause of death and disability in the US, and SARS-CoV-2 COVID-19 the third leading cause of death. As reported extensively, many COVID patients admitted to BUSM with severe pulmonary pathologies also had inflammatory cardiovascular (CV) pathologies that increase the likelihood of major adverse cardiovascular events (MACE) during hospitalization and often after discharge. Rapid and reliable detection of COVID is crucial, since MI can occur as early as 2 days after admission. Detection and therapy will be enhanced by our mechanistic studies of heart fatty acid binding protein (H-FABP). Our study is based on the hypothesis that cardiovascular events and inflammation will be detected by leakage of H-FABP, after cardiomyocyte membrane damage. H- FABP is a small soluble intracellular molecule found almost exclusively in the cardiomyocyte cytoplasm has been used as a clinical measure of damage in patients with heart failure and myocardial infarction (MI). It has been shown to be a sensitive, rapid, and specific assay for detecting CVD quickly upon admission. Our in vitro cell studies demonstrated that H-FAB measured by ELISA is a sensitive and reliable biomarker of cardiomyocyte damage induced by lipopolysaccharide (LPS), and healing of the membrane by RvE1,a specialized pro-resolving mediator (SPM) derived from the Omega-3 fatty acid, eicosapentaenoic acid (EPA), a dietary nutrient that balances inflammation to restore homeostasis. EPA has also been shown to promote muscle repair after MI.
Methods: Using commercial ELISA sandwich assays, we tested our hypothesis that H-FABP will be detected in the supernatant of cells after cardiomyocyte membrane damage and in the blood of patients with COVID and/or other inflammatory comorbidities. Blood samples were diluted 1:15 in sample diluent provided by the commercial human H-FABP ELISA kit. To induce cardiomyocyte cell membrane damage we applied the Endotoxin lipopolysaccharide (LPS) in cultured immortalized cardiomyocytes and stem cell-derived cardiac cell systems, to induce cell membrane damage and inflammation. ELISA assays showed instantaneous concentration-dependent leakage of H-FABP into the buffer of cultured cardiomyocytes, and H-FABP was significantly decreased in cells treated by resolvins. The assay was processed through a microplate reader at 450 nm to obtain the quantitative value entered in our graphs and tables. After establishing the reproducibility of the high sensitivity of H-FABP, we tested our hypothesis that inflammation-lowering therapeutics (RvE1) will reduce the damage by LPS to heart cells and that can be validated by decreased leakage of H-FABP by the ELiSA methods in 12-well plates. For quantification of H-FABP, supernatant samples were centrifuged after collection and diluted 1:10 in sample diluent provided by the ELISA kit. We obtained blood samples from the BMC COVID biorepository, which collects blood from patients upon admission to the hospital. This biorepository has clinical information, such as demographics, disease severity, treatments, complications, and comorbidities (such as End Stage Renal Disease).
Results: Conditions for measuring H-FABP for injury and therapy. Dose-dependent and time- dependent amounts of H-FABP released from cardiomyocytes into the media supernatant were measured by ELISA..
Increased LPS exposure resulted in an increased H-FABP concentration (p < 0.05, Lipopolysaccharide was used in cultured cells as a model for inflammation damage to optimize standard error = 0.071, N = 33), showing that heart muscle damage can originate at a cellular level. H-FABP was detected at low concentrations (ng/ml). The addition of RvE1 caused decreased leakage of H-FABP, which validates our hypothesis of inflammation as a mechanism of injury. The treatment with RVE1 was dose- and time-dependent With a 4 hour incubation, H-FABP concentration decreased by 72.3%. With a 24 hour incubation, H-FABP concentration decreased by 99.4%.H-FABP was a highly sensitive biomarker in the blood assays and reflected the type and number of comorbidities. Patients with 2 or 3 comorbidities had statistically higher blood H-FABP than those with 1 or no comorbidities (unpaired two-tailed t-tests: p = 0.0001 for both non-COVID patients and COVID patients). Patients with a COVID history also had statistically higher H-FABP than patients without recent COVID history (unpaired two-tailed t-test: p = 0.0063, N = 9). H-FABP provided remarkable differentiation of patients with no comorbidities and one or more comorbidities in both groups. Additionally, higher H-FABP concentrations were found in patients with diagnosed ESRD (p = 0.0009). The kidney normally contains a low amount of H-FABP, but higher amounts have been attributed to an accumulation of damaged cardiac cells in the filtration of the blood and entrapment in dense glomerular structures.
Conclusions: Since the early studies linking CVD to other risk factors, SARS-CoV-2 infection has been documented to increase inflammation of the heart muscle in up to 60% of patients recovering from COVID-19. As the authors conclude, there still is not a clear link between risk factors and long term problems. There is increasing evidence that long term SARS-CoV-2 infection greatly increases the risk of long-term kidney disease. Our proposed H-FABP measurements in patient blood with identified inflammatory-driven comorbidities emphasize the unique value of H-FABP in monitoring comorbidities with multiple risk factors, including ESRD, CVD), and diabetes. A major gap in the healthcare of patients is the need for continuous attention for cardiac injury and whether comorbidities improve with timely treatment, which will be enhanced by our therapy with RvE1 and other SPMs to prevent further cardiac issues. Early identification, diagnosis, and treatment decrease the risk of further downstream adverse health consequences. Our study promotes and provides a basis for the standardization of criteria with highly validated blood biomarkers that encompass heart, vascular, and other organ pathologies that will enable informed decision-making by physicians. Our studies support a unifying mechanistic hypothesis of high systemic inflammation and therapy based on inflammation resolution that can be achieved by lifestyle changes to supplement proven therapeutics for the acute treatment of infection. The cohort of the study will benefit from inexpensive therapeutics and from a holistic approach. It has been shown that SARS-CoV-2 spike protein, which is highly infectious, binds to LPS and boosts proinflammatory activity. The spike protein is bound to the SARS-CoV-2 virus membrane and desorbs rapidly, which facilitates systemic viral infection, We will perform parallel trials of damage and healing in cardiomyocytes with purified spike protein, which does not require the restrictions a BL3 lab for studies of the SARS-CoV-2 viral particles.
Disclosures: Nothing to disclose by any author(s)
15Sitosterolemia: An Atypical Case of Compound Heterozygous Mutation in ABCG5 in a Young Puerto Rican Male
Karen N. Yelton Torres, Oswald Mora Osoria, Jose M. García Mateo
Hospital Damas
Purpose: Sitosterolemia, is a rare disorder of lipid metabolism, caused by loss of function mutations in the “ATP-binding cassette subfamily G” (ABCG5 and ABCG8) genes located in a head-to-head human chromosome 2p21, as an autosomal recessive condition. Sitosterolemia is more prevalent in Middle Eastern population and can be inherited as a homozygous or compound heterozygous pattern. Regarding pathophysiology, this condition is characterized by increased intestinal absorption and decreased biliary excretion of dietary sterols, hypercholesterolemia and premature coronary atherosclerosis. As a result of this disorder in lipoprotein metabolism, patients with this condition can have phenotypical variations regarding the presence of tuberous xanthomas, elevated plasma cholesterol and phytosterol levels, thrombocytopenia and hemolytic anemia. This condition even though is more prevalent in the Middle Eastern population, can also be found in Hispanic population as well. It is of great importance, to include this condition as part of our differential diagnosis when we encounter young patients with hypercholesterolemia and perform genetic panel testing to aid in the management and treatment of this rare disorder of lipid metabolism.
Methods: Case report of a 21-year-old Puerto Rican young man that presents with hypercholesterolemia to our endocrinology and lipidology clinic. Complete laboratory workup and genetic testing panel results confirmed diagnosis of sitosterolemia. Patient currently continues medical follow up on our clinic after starting ezetimibe therapy.
Results: This case report involves a 21-year-old Puerto Rican man who presented to our endocrinology and lipidology clinic with elevated LDL-C levels since late childhood. He had no prior genetic testing or medical treatment and denied chest pain, shortness of breath, palpitations, or cardiovascular events. Physical examination was unremarkable, with no corneal arcus or tendinous xanthomas.
His lipid profile showed total cholesterol 290 mg/dL, LDL-C 217 mg/dL, triglycerides 69 mg/dL, and HDL-C 59 mg/dL. A genetic panel revealed a compound heterozygous mutation (c.914C>G, p.(Thr305Arg) in the ABCG5 gene, resulting in a diagnosis of sitosterolemia. Elevated plasma sitosterol levels confirmed the diagnosis. The patient was advised to follow a low cholesterol/low plant sterol diet and was prescribed ezetimibe. At a follow-up appointment 12 weeks later, his lipid profile showed total cholesterol 231 mg/dL, LDL-C 164 mg/dL, triglycerides 104 mg/dL, and HDL-C 59 mg/dL. Ezetimibe works by inhibiting the NPC1L1 transporter, crucial for cholesterol absorption in the small intestine, effectively reducing the amount of cholesterol entering the bloodstream and lowering LDL-C levels. Despite the underlying genetic condition, ezetimibe reduced LDL-C by 24%, demonstrating its role in managing cholesterol in this rare genetic disorder. The patient’s dietary modifications and ezetimibe therapy will require ongoing evaluation to optimize lipid levels and manage the condition effectively. Although the ABCG5 mutation is more prevalent in the Middle Eastern population, this case has been found to be one of the eight individuals heterozygous for this variant. These heterozygous mutations in ATP-binding cassettes play an important role in the absorption of dietary and biliary sterols in the liver and their excretion into bile. Accumulated plant sterols in hepatocytes inactivate SREBP-2, downregulating hepatic LDL-R expression and decreasing serum LDL-C uptake, leading to a poor response to statins.
Conclusions: This case report highlights the importance of genetic testing and comprehensive evaluation for an accurate diagnosis, as other pathologies like Familial Hypercholesterolemia can present similarly but differs in management. While more common in Middle Eastern populations, this case also highlights sitosterolemia’s presence in Hispanic individuals, emphasizing the need for increased awareness and understanding in diverse populations.
Disclosures: Nothing to disclose by any authors
24Subgroup Analysis by Gender and Body Mass Index (BMI) in People Living With Overweight/Obesity in the Survodutide, a Glucagon/GLP-1 Receptor Dual Agonist, Phase II Trial
Carel W. le Roux, Oren Steen, Kathryn J. Lucas, Elena Startseva, Anna Unseld, Anita M. Hennige
St. Vincent’s University Hospital and University College Dublin School of Medicine, Dublin, Ireland;Private practice, Toronto, Ontario, Canada;Diabetes & Endocrinology Consultants PC, Morehead City, NC, USA;Boehringer Ingelheim International GmbH, Ingelheim, Germany;Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach/Riss, Germany;Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach/Riss, Germany
Purpose: To explore the effect of gender and body mass index (BMI) on weight loss and adverse events with survodutide in people living with overweight/obesity.
Methods: In this double-blind, placebo (PBO)-controlled Phase II trial (NCT04667377), 387 adults with BMI ≥27 kg/m2 without diabetes were randomized 1:1:1:1:1 to weekly subcutaneous survodutide (0.6, 2.4, 3.6, 4.8mg) or PBO over 46 weeks. Percentage change in body weight (primary endpoint), absolute change in body weight and waist circumference (secondary endpoints), and adverse events (AEs) were assessed in subgroups based on gender and BMI at baseline (BL). Data were analyzed descriptively for all participants who received ≥1 dose of study drug and had data for ≥1 efficacy endpoint (full analysis set [FAS];planned treatment: n=384).
Results: Of 384 participants, 68.2% (262) were female. At BL, 9.9% (38), 30.5% (117), 31.8% (122), and 27.9% (107) had a BMI of <30, 30–<35, 35–<40, and ≥40kg/m2, respectively. Demographics and clinical characteristics at BL were similar between males and females and across BMI subgroups. At Week 46, mean percentage change in body weight from BL with survodutide 4.8mg vs PBO was –11.9% vs –3.3% in males and –17.0% vs –3.2% in females, and –19.1% vs –1.7%, –15.8% vs –3.1%, –15.4% vs –5.8%, and –13.4% vs –0.8% across BL BMI categories. Mean absolute body weight loss from BL (survodutide 4.8mg vs PBO) was –15.9 vs –4.2kg in males and –22.0 vs –3.0kg in females. Reductions in absolute body weight with survodutide 4.8mg vs PBO were similar across BMI subgroups: –21.3 vs 1.4kg, –16.2 vs –3.3kg, –22.2 vs –7.5kg, and –19.9 vs –1.6kg. Mean absolute change in waist circumference from BL (survodutide 4.8mg vs PBO) was –12.8 vs –1.7cm in males and –17.9 vs –4.9cm in females, and –8.4 vs –2.6cm, –14.3 vs –6.4cm, –17.5 vs –5.0cm, and –17.2 vs 3.3cm across BL BMI categories.
A higher proportion of participants lost ≥15% of BL body weight with survodutide 4.8mg vs PBO: 31.8% vs 9.5% in males and 66.7% vs 3.0% in females, and 75.0% vs 14.3%, 57.9% vs 4.5%, 52.0% vs 6.7%, and 50.0% vs 0.0% across BL BMI categories;respectively. All survodutide doses (pooled) were tolerated across gender and BL BMI subgroups. In males vs females, rates of any AE (87.9% vs 92.4%), serious AEs (4.0% vs 4.3%), and discontinuations due to AEs (25.3% and 24.3%) were comparable. Gastrointestinal AEs with all survodutide doses were experienced by fewer males (65.7%) than females (79.5%);mild to moderate nausea was the most frequently reported gastrointestinal AE in both subgroups.
Conclusions: After 46 weeks of survodutide treatment, females appeared to lose more body weight and waist circumference than males. Participants with a lower vs higher BL BMI generally lost more proportional body weight, with an opposite trend observed for waist circumference. *This is an encore abstract
Disclosures: CWLR has received personal fees from Boehringer Ingelheim, Eli Lilly, GI Dynamics, Gila Pharmaceuticals, Herbalife, Johnson & Johnson, Keyron, Novo Nordisk, and Zealand Pharma outside the submitted work;OS has received research support from Alnylam, Anji, AstraZeneca, Boehringer Ingelheim, CRISPR Therapeutics, Eli Lilly, Gilead Sciences, Janssen, Kowa, Medicago, Moderna, Novartis, Novo Nordisk, Pfizer, Sanofi, ViaCyte and Zucara Therapeutics;speaker bureau fees from Abbott, Amgen, AstraZeneca, Bausch Health, Boehringer Ingelheim, Eli Lilly, Janssen, LMC, Novo Nordisk and Sanofi;and consultancy fees from Amgen, Bayer, Eli Lilly, Novo Nordisk and Sanofi;KJL declares no conflicts of interest;ES, AU, and AMH are employees of Boehringer Ingelheim
This encore abstract was originally presented at ENDO 2024 (Boston, MA, USA; June 1–4, 2024)
22Survodutide, a glucagon receptor/GLP-1 receptor (GCGR/GLP-1R) dual agonist, improves cardiometabolic parameters in adults with obesity: analysis of a placebo-controlled, randomised phase 2 trial
Carel W. le Roux, Oren Steen, Kathryn J. Lucas, Elif I. Ekinci, Elena Startseva, Anna Unseld, Anita M. Hennige
St. Vincent’s University Hospital and University College Dublin School of Medicine, Dublin, Ireland;Private practice, Toronto, Ontario, Canada;Diabetes & Endocrinology Consultants PC, Morehead City, NC, USA;Austin Health, Heidelberg, Victoria, Australia;The Australian Centre for Accelerating Diabetes Innovation, University of Melbourne, Parkville, Australia;and Melbourne Medical School, University of Melbourne, Melbourne, Victoria, Australia;Boehringer Ingelheim International GmbH, Ingelheim, Germany;Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany;Boehringer Ingelheim International GmbH, Biberach, Germany
Purpose: Obesity increases the risk of cardiovascular disease and contributes to cardiovascular risk factors, such as hypertension and dyslipidemia. Survodutide is a GCGR/GLP-1R dual agonist in clinical development for obesity. In a phase 2 clinical trial in individuals with obesity without diabetes (NCT04667377), survodutide elicited up to 18.7% mean reduction in body weight after 46 weeks (primary endpoint) according to actual treatment. We explored the effect of survodutide on cardiometabolic parameters in this trial cohort.
Methods: 387 people aged ≥18 to <75 years with body mass index (BMI) ≥27 kg/m2 without diabetes were randomized 1:1:1:1:1 to once-weekly subcutaneous survodutide (0.6, 2.4, 3.6, 4.8 mg) or placebo for 46 weeks, comprising an initial 20-week escalation period when the dose could be adjusted for gastrointestinal tolerability, followed by a 26-week maintenance period. We evaluated changes from baseline to week 46 in waist circumference;lipid parameters (triglyceride [TG], high-density lipoprotein [HDL], very low-density lipoprotein [VLDL], low-density lipoprotein [LDL], total cholesterol [TC], and non-HDL cholesterol [non-HDL-C]);and blood pressure by presence or absence of hypertension before and at screening. Data were analyzed descriptively for all participants receiving ≥1 dose of study drug with data for ≥1 efficacy endpoint, i.e. full analysis set (FAS), according to doses received during the maintenance period (actual treatment) and according to doses assigned at randomization (planned treatment) using on-treatment data.
Results: In the FAS (n=384), baseline demographic and clinical characteristics were similar across treatment groups: overall mean age 49.1 years, BMI 37.1 kg/m2, 262 (68.2%) female, 301 (78.4%) White, 40 (10.4%) Asian, and 37 (9.6%) Black. Before and at screening, 133 (34.6%) participants had hypertension and 108 (28.1%) had dyslipidemia. Waist circumference was reduced in all survodutide doses vs placebo;the largest mean reduction was 16.6 cm (4.8 mg group;actual treatment). Survodutide was associated with reductions of up to 10.2 mmHg in systolic blood pressure and 4.8 mmHg in diastolic blood pressure from baseline to week 46 by actual treatment;similar reductions were observed for planned treatment, and reductions were comparable with or without hypertension before and at screening. A marked decrease in mean TG was observed in all survodutide groups by planned treatment. Mean HDL was relatively unchanged over the period. Small decreases occurred in mean VLDL (all survodutide doses) and mean LDL (2.4 and 3.6 mg doses). Mean TC and non-HDL-C decreased in 0.6, 2.4, and 3.6 mg groups.
Conclusions: In people living with obesity, the GCGR/GLP-1R dual agonist survodutide was associated with clinically meaningful reductions in waist circumference, blood pressure (with or without hypertension before and at screening), and TG. *This is an encore abstract
Disclosures: CWLR has received personal fees from Boehringer Ingelheim, Eli Lilly, GI Dynamics, Gila Pharmaceuticals, Herbalife, Johnson & Johnson, Keyron, Novo Nordisk, and Zealand Pharma outside the submitted work. OS has received research support from Alnylam, Anji, AstraZeneca, Boehringer Ingelheim, CRISPR Therapeutics, Eli Lilly, Gilead Sciences, Janssen, Kowa, Medicago, Moderna, Novartis, Novo Nordisk, Pfizer, Sanofi, ViaCyte and Zucara Therapeutics;speaker bureau fees from Abbott, Amgen, AstraZeneca, Bausch Health, Boehringer Ingelheim, Eli Lilly, Janssen, LMC, Novo Nordisk and Sanofi;and consultancy fees from Amgen, Bayer, Eli Lilly, Novo Nordisk and Sanofi. KJL declares no conflicts of interest. EIE is a consultant to Bayer and Eli Lilly Australia, and her institute reports research funding support from Amgen, Bayer, Boehringer Ingelheim, Eli Lilly Australia, and Versanis. ES, AU, and AMH are employees of Boehringer Ingelheim.
This encore abstract was originally presented at European Society of Cardiology (ESC) Congress 2024 (London, UK/Hybrid; August 30–September 2, 2024)
30Temporal trends analyzing the impact of chronic obstructive pulmonary disease on congestive heart failure related mortality statistics.
Shaaf Ahmad 1, Kaleem Maqsood 2, Uzair Nisar Malik 3, , Muhammad Amir 2, Husna Ahmad 2
- University of North Carolina at Chapel Hill, 2. The University of the Punjab, 3. King Edward Medical University
Purpose: COPD, the fifth most common chronic disease worldwide, is a slowly progressing pulmonary disorder with an underlying component of systemic inflammation. Low circulating levels of oxygen, alterations in pulmonary vessel hemodynamics and elevated levels of cytokines are all implicated in inducing cardiovascular dysfunction in patients with COPD. This analysis aims to determine the impact of targeted interventions directed against reducing the heart failure-related mortality burden in patients with COPD.
Methods: CDC WONDER database was queried from 1999-2021. Only patients younger than 54 years old were included. Age-adjusted mortality rates (AAMR) per 100,000 with 95% confidence intervals were obtained. Joinpoint® 5.0 software was used to analyze trend shift using log-linear regression to calculate the average annual percent change (AAPC) values.
Results: The overall AAMR attributable to CHF in patients with CHD increased from 5.5 (5.4, 5.6) in 1999 to 7.0 (7.0, 7.1) in 2019 (AAPC: 1.6;1.3, 2.0). Oklahoma, Kentucky, Mississippi and Arkansas recorded mortality rates above the 90th percentile. Whereas, mortality was the lowest in New York, New Jersey, Florida and Hawaii. When stratifying by sex, males (7.8;7.7, 8 [AAPC: 0.9]) experienced higher mortality rates than the females (6.5;6.4, 6.6 [AAPC: 2.1]), but the females experienced a greater increase in their AAMRs. CHF-related mortality was the highest among the NH Whites with COPD (AAMR-overall: 9.2;9.2, 9.3) and the lowest in the Asians and Pacific Islanders (AAMR-overall: 1.2;1.1, 1.2). The AAMRs for the residents of rural counties were three times as high as those for large city dwellers. (AAMR-rural: 12.5;12.4, 12.6 versus AAMR-metro: 4.6;4.6, 4.6).
Conclusions: CHF continues to be a prime contributor to mortality in patients with underlying COPD. Despite aggressive measures, the mortality rates have risen in the past two decades, with significant sociodemographic disparities. Our paper strives to highlight the need for early identification, and an aggressive and proactive management of heart failure in patients with chronic obstructive pulmonary disease.
Disclosures: Nothing to disclose by any author(s)
11The Hidden Divide: Examining Inequities in Healthcare Provider Training and Practices
Suketu Patel, MD, PhD1, Eirasmin Lokpez-Cobo, MA, MS2, Brianna Calderon-Roman, MS2,, Jarvier Mohammed, PhD1
- Havas Health Network
- Republica Havas Health
Purpose: The purpose of this study is to examine the persistent inequities in healthcare provider (HCP) training and practices, which are key drivers of health disparities and particularly affect marginalized populations. While efforts over the past few decades have focused on social determinants of health, systemic barriers within healthcare providers remain underexplored and largely unaddressed. In line with this, data demonstrates that multicultural patients with cardiometabolic diseases face significant healthcare disparities. This study focuses on three key contributors to inequitable HCP care: medical bias, lack of representation, and inadequate cultural competence. By assessing existing literature, we sought to uncover how these factors impact patient outcomes and propose actionable strategies for education, healthcare, and pharmaceutical stakeholders to initiate impactful, equity-driven changes in clinical settings.
Methods: This study employs a comprehensive literature review to synthesize existing knowledge on inequities in healthcare provider training and practices. We systematically reviewed peer-reviewed journal articles, public policy documents, health policy studies, and national socio-demographic data. We did a deep dive on reports that contextualize the impact of demographic shifts in the U.S. population on the demand for equitable healthcare, and publications on educational gaps in medical training, cultural competence mandates, and systemic barriers within healthcare organizations. This comprehensive review enabled a multi-faceted analysis that integrates both academic and practical perspectives, offering insights that are directly applicable to education, healthcare, and pharmaceutical stakeholders.
Results: Our analysis revealed three overarching contributors to inequities in healthcare provider training and practices: medical bias, lack of representation among healthcare providers, and inadequate cultural competency training. Medical biases, both conscious and unconscious, were shown to significantly affect patient care decisions, leading to delayed diagnoses, inappropriate treatments, and overall poorer outcomes for marginalized groups.
Lack of representation in the medical workforce—particularly among racial, ethnic, and gender minorities—further perpetuates health disparities by eroding trust and communication between patients and providers. This disconnect often results in misdiagnoses and reluctance to seek care. Inadequate cultural competency training exacerbates these issues, as healthcare providers are often unprepared to effectively communicate with or treat patients from diverse backgrounds. These findings underscore the importance of integrating cultural competency and humility into medical education and training. Several strategies are proposed to address these gaps. Increasing diversity in medical schools through targeted recruitment and scholarship programs will create a healthcare workforce that reflects the patients it serves, fostering trust and improving outcomes. Mentorship programs and inclusive support systems are critical to empowering minority medical students, while revamping curricula and enforcing cultural competence training will enhance providers’ ability to offer equitable care. In addition, healthcare organizations can further promote inclusion through bias training, partnerships with cultural experts, and culturally relevant healthcare communications grounded on a patient-centric approach. Enhancing diversity in clinical trials, engaging community leaders, and empowering Advanced Practice Providers (APPs) as cultural navigators will also improve outcomes for diverse populations. These strategies offer a pathway to reducing healthcare disparities and improving outcomes for all patient populations, especially those who are underserved.
Conclusions: This study highlights critical gaps in healthcare provider training and practices that contribute to health inequities. Addressing healthcare inequities requires a multifaceted approach that targets medical bias, enhances representation, and improves cultural competency. As the U.S. becomes increasingly diverse, the need for culturally competent, patient-centered care will become even more critical. The evidence strongly supports the notion that equitable healthcare cannot be achieved solely through patient-focused interventions; healthcare providers play a pivotal role in either perpetuating or dismantling systemic barriers. Medical education, healthcare, and pharmaceutical organizations can lead this transformation. By implementing targeted recruitment and mentorship programs, revising medical education curricula, and fostering inclusive practices we can build a more diverse and culturally competent healthcare workforce. These efforts, coupled with community engagement and culturally relevant care and communications, will help reduce disparities, improve patient outcomes, and create a more equitable healthcare system for all.
Disclosures: Nothing to disclose by any authors.
35Utilization of High-Sensitivity C-Reactive Protein Testing in Primary and Secondary ASCVD Prevention
Emil deGoma, Yung Chyung, John Walsh, C. William Pike, Jananee Muralidharan, Vincent Marino, J. Craig Davis, Saurabh Gombar, Michael D. Shapiro
Tourmaline Bio, Inc., Atropos Health, Wake Forest University School of Medicine
Purpose: Ongoing clinical trials incorporate high-sensitivity C-reactive protein (hs-CRP) as a prognostic and predictive biomarker of ASCVD risk to help enrich for high-risk patients who may derive greater benefit from novel anti-inflammatory therapies. Hs-CRP is a widely available, inexpensive, standardized, and validated test that stratifies risk in both primary and secondary settings. Independent of other risk factors, higher levels of hs-CRP have been strongly associated with an increased risk of major adverse cardiovascular events. Despite the incorporation of hs-CRP testing into risk assessment guidelines, characterization of its utilization remains limited. As such, we sought to characterize the use of hs-CRP testing in ASCVD prevention settings.
Methods: We analyzed risk factors, ASCVD, and hs-CRP testing from EVERSANA EHR Integrated Database, a nationally representative electronic health records database, from 1 Jan 2016 to 8 Nov 2023. Analysis of the primary prevention population focused on high-risk patients, defined as those age 50 years or older with the diagnosis of diabetes or 2 or more of the following risk factors: tobacco use, hyperlipidemia, or hypertension. Sensitivity analyses were conducted to exclude patients with concomitant inflammatory or infectious diseases.
Results: In our dataset, only 25,550 (0.7%) of 3.7 million secondary prevention patients and 20,925 (0.3%) of 6.5 million high-risk primary prevention patients had any hs-CRP measurement. Analysis by year showed no meaningful changes in hs-CRP utilization from 2016 to 2023. Among secondary prevention patients who had any hs CRP recorded, median age was 64 years, 52% were men, and median hs-CRP was 3.3 mg/L. Excluding secondary prevention patients with a concomitant diagnosis of inflammatory or infectious disease or hs-CRP>20 mg/L, median hs-CRP was 1.7 mg/L, with hs-CRP ≥2 mg/L and ≥3 mg/L observed in 46% and 34%, respectively.
Conclusions: In the US, the use of hs-CRP testing in primary and secondary prevention of ASCVD is low. Among patients with hs-CRP tested, the prevalence of systemic inflammatory risk was high. Enhancing education on the clinical benefits of hs-CRP testing may facilitate tailoring of treatment intensity and modality more closely to ASCVD risk profiles.
Disclosures: EdG, YC, and JW are employees of Tourmaline Bio. CWP, JM, VM, JCD, and SG are employees of Atropos Health, contracted by Tourmaline Bio. MDS is supported by institutional grants from Amgen, Arrowhead, Boehringer Ingelheim, 89Bio, Esperion, Novartis, Ionis, Merck, New Amsterdam, and Cleerly;has participated in scientific advisory boards with Amgen, Agepha, Ionis, Novartis, New Amsterdam, and Merck;and has served as a consultant for Ionis, Novartis, Regeneron, Aidoc, Shanghai Pharma Biotherapeutics, Kaneka, Novo Nordisk, Arrowhead, and Tourmaline.
