Beneficial CV effects of tirzepatide in patients with HFpEF and obesity

This summary is based on the presentation of Milton Packer, MD (Dallas, TX, US) at the AHA Scientific Sessions 2024 – Effect of Tirzepatide on Major Heart Failure Outcomes in Patients With Heart Failure With a Preserved Ejection Fraction and Obesity: The SUMMIT Trial.

Introduction and methods

Obesity – and in particular visceral adiposity – plays a key role in the development of HFpEF. Treatment with the dual GIP/GLP-1RA tirzepatide leads to substantial weight loss in people with obesity, but it is unclear whether this drug has beneficial effects on cardiovascular outcomes. The SUMMIT trial evaluated whether treatment with the dual GIP/GLP-1RA tirzepatide improves cardiovascular outcomes in patients with HFpEF and obesity.

The SUMMUT trial was an international, double-blind, phase 3, placebo-controlled trial, in which 731 patients with HFpEF and obesity were randomized to tirzepatide or matching placebo. Patients in the tirzepatide group received a starting dose of tirzepatide 2.5 mg once weekly and doses were escalated to maximally tolerated dose of 15 mg once weekly by 20 weeks. Median duration of follow-up was 104 (IQR: 66-126) weeks.

The first primary endpoint was a composite of cardiovascular mortality or worsening HF events and the second primary endpoint was the change in KCCQ-Clinical Summary Score (CSS) from baseline to 52 weeks.

Main results

• Tirzepatide reduced time-to-first-event for cardiovascular mortality or worsening HF compared with placebo (HR: 0.62: 95%CI: 0.41-0.95; RR: 38%; P=0.026).
• This benefit was driven primarily by worsening HF events requiring hospitalization or urgent intravenous drugs for HF (HR: 0.41; 95%CI: 0.22-0.75; P=0.004).
• Treatment with tirzepatide led to a larger improvement in KCCQ-CSS from baseline to 52 weeks compared with placebo (between-group mean difference: 6.9 points; 95%CI: 3.3-10.6; P<0.001).
• The treatment effects of tirzepatide on the two co-primary endpoints were consistent across all predefined subgroups.
• At 52 weeks, treatment with tirzepatide vs. placebo improved 6-minute walk distance (6MWD; difference: +18.3 meters; 95%CI: 9.9-26.7; P<0.001), body weight (difference; -11.6%; 95%CI: -12.9 to -10.4; P<0.001) and hsCRP levels (difference; -34.9%; 95%CI: -45.6 to -22.2; P<0.001).
• The safety profile of tirzepatide in this study was consistent with prior trials with tirzepatide. A total of 4.1% patients in the tirzepatide group discontinued treatment due to gastrointestinal side effects.

Conclusion

In the SUMMIT trial, tirzepatide reduced the composite of cardiovascular mortality and worsening HF events in patients with HFpEF and obesity compared with placebo. This effect was driven by worsening HF events. Tirzepatide also improved health status as assessed with KCCQ-CSS, 6MWD, body weight and hsCRP levels.

- Our reporting is based on the information provided at the AHA Scientific Sessions 2024 -

The findings of this study were simultaneously published in N Eng J Med.

Watch a video with Milton Packer about SUMMIT