Post hoc analysis of SURMOUNT-J: tirzepatide versus placebo and predicted 10-year cardiovascular disease risk in Japanese adults with obesity disease

Objective Obesity management is central to reducing cardiovascular disease (CVD) risk. In the phase 3 SURMOUNT-J trial, tirzepatide significantly reduced body weight and improved cardiometabolic parameters versus placebo in Japanese adults with obesity disease (as defined by the Japan Society for the Study of Obesity JASSO, referring to obesity requiring clinical treatment) and without diabetes. We conducted post hoc analyses to predict 10-year CVD risk and the number of potentially preventable CVD events based on predicted risk with tirzepatide versus placebo.Methods Adults meeting the JASSO criteria for obesity disease and without prior CVD received once-weekly tirzepatide (10 mg or 15 mg) or placebo for 72 weeks. Change in predicted 10-year CVD risk was assessed from baseline to Week 72 using Framingham risk equations. The number of potentially preventable CVD events was projected using national statistics and the Medical Data Vision database.Results Among 186 participants who completed treatment (n = 64, tirzepatide 10 mg; n = 59, tirzepatide 15 mg; n = 63, placebo), mean predicted 10-year CVD risk at baseline was 12.6%. Tirzepatide treatment was associated with significant reductions in predicted 10-year CVD risk at Week 72, with mean absolute reductions from baseline of 2.8% (95% confidence interval CI: −3.7%, −1.9%) (10 mg) and 2.5% (95% CI: −3.4%, −1.6%) (15 mg) versus an increase of 2.0% (95% CI: 1.1%, 2.9%) with placebo (model-derived hazard ratios 0.65 and 0.68, respectively, p < 0.001). Reduction in predicted risk was evident by Week 8 and sustained through Week 72. Extrapolated to approximately 5.1 million estimated treatment-eligible individuals in Japan without prior CVD, the projected model-based estimate for number of potentially preventable CVD events with tirzepatide treatment (10 mg) is 123,000 CVD events over 10 years, compared with an estimated increase of 88,000 events with placebo.Conclusions In this post hoc analysis, tirzepatide treatment was associated with a significant reduction in predicted 10-year CVD risk versus placebo, which was associated with an increase in predicted risk, supporting the potential role of tirzepatide in primary CVD prevention.Clinical trial registration ClinicalTrials.gov, NCT04844918.