SAT658 Tirzepatide Reduces The Predicted Risk Of Developing Atherosclerotic Cardiovascular Disease: A Post-hoc Analysis Of The Surmount-1 Trial

Disclosure: E.R. Hankosky: Employee; Self; Eli Lilly & Company. Stock Owner; Self; Eli Lilly & Company. H. Wang: Other; Self; Eli Lilly & Company. N.M. Lisa: Employee; Self; Eli Lilly & Company. Stock Owner; Self; Eli Lilly & Company. H. Kan: Employee; Self; Eli Lilly & Company. Stock Owner; Self; Eli Lilly & Company. F. Wang: Employee; Self; Eli Lilly & Company. Stock Owner; Self; Eli Lilly & Company. N.N. Ahmad: Employee; Self; Eli Lilly & Company. Stock Owner; Self; Eli Lilly & Company. A. Stefanski: Grant Recipient; Self; Eli Lilly & Company. Employee; Self; Eli Lilly & Company. Stock Owner; Self; Eli Lilly & Company. W. Garvey: Consulting Fee; Self; Eli Lilly & Company, Novo Nordisk, Boehringer Ingelheim, Pfizer, Inc., Fractyl Laboratories, Merck. Grant Recipient; Self; Eli Lilly & Company, Novo Nordisk, Pfizer, Inc. Background: Tirzepatide (TZP) resulted in substantial and sustained body weight reduction among participants with obesity or overweight in SURMOUNT-1, a phase 3 randomized clinical trial. Using predictive modelling, the current study assessed the impact of TZP treatment on the 10-year risk of developing atherosclerotic cardiovascular disease (ASCVD) among SURMOUNT-1 participants. Methods: The American College of Cardiology/American Heart Association (ACC/AHA) risk engine was applied to data from SURMOUNT-1 participants free of ASCVD at baseline. ASCVD risk scores were calculated at baseline, 24, and 72 weeks. The model inputs were age, total cholesterol, high density lipoprotein, systolic blood pressure, hypertension treatment, diabetes, and smoking status. Mean percent change in the 10-year risk score from baseline to week 72 was compared between TZP groups and placebo (PBO) using Mixed Model for Repeated Measures (MMRM), adjusted for baseline risk scores and country; risk scores were analyzed on log-scale. Since the risk score was low in the overall SURMOUNT-1 population, a subgroup analysis was conducted in participants with higher ASCVD risk at baseline (score≥7.5%, ACC/AHA intermediate-to-high risk). Results: A total of 2461 participants (TZP 5 mg, n=614; 10 mg, n=616; 15 mg, n=609; PBO, n=622) were included (mean age=45 years; female=68%; White=70%). At baseline, the median 10-year predicted risk score ranged from 1.5%–1.6% and did not differ across treatment groups. Median absolute risk scores for TZP 5/10/15 mg and PBO groups were 1.4%, 1.2%, 1.3%, and 1.6% at week 24, and 1.3%, 1.2%, 1.1%, and 1.7% at week 72, respectively. At week 72, MMRM-estimated relative change in risk from baseline was -16.4%, -23.5%, -22.4%, and 12.7% for TZP 5/10/15mg and PBO, leading to significantly greater reduction for TZP groups compared to PBO (TZP 5 mg: -25.8%; 10 mg: -32.1%; 15 mg: -31.1%; p≤0.001). Among 272 participants (TZP 5 mg, n=83; 10 mg, n=66; 15 mg, n=55; PBO, n=68) with intermediate-to-high baseline ASCVD risk, median risk scores for TZP 5/10/15 mg and PBO groups were: baseline: 11.3%, 10.5%, 10.9%, 10.1%; week 72: 11.3%, 9.0%, 10.3%, 11.7%, respectively. MMRM-estimated relative risk reduction at week 72 was -10.3%, -20.6%, -16.1%, and 6.4% for TZP 5/10/15 mg and PBO groups, respectively. Consistent with the primary analysis, relative risk reduction was significantly greater in TZP groups compared to PBO (TZP 5 mg = -15.7%; 10 mg = -25.3%; 15 mg = -21.1%; p≤0.01). Conclusion: TZP treatment significantly reduced the 10-year predicted risk of developing ASCVD compared to PBO, though the magnitude of reduction in absolute risk scores was small due to low baseline risk in the overall population. Among participants with higher ASCVD risk at baseline, TZP treatment resulted in larger absolute reductions in risk along with significant relative risk reduction consistent with the primary analysis. Presentation: Saturday, June 17, 2023