Key Points
- SUMMIT was a multi-national trial that compared cardiovascular outcomes among patients with heart failure with preserved ejection fraction (HFpEF) and obesity that were randomized to tirzepatide (a GLP-1 receptor agonist) or placebo.
- Patients in the tirzepatide arm had a significantly lower risk of a composite of worsening heart failure events and cardiovascular death, driven by a reduction in heart failure events. In addition, they experienced significantly larger gains in health status and physical functioning compared to placebo.
Tirzepatide is currently approved by the US Food and Drug Administration for the treatment of type 2 diabetes as well as weight management among those with diabetes. While it is established that obesity can contribute to worsening heart failure and that tirzepatide is very effective at inducing weight loss, the impact of tirzepatide on cardiovascular outcomes among patients with HFpEF and obesity is uncertain.
On November 16, 2024 the results of “Tirzepatide for Heart Failure with Preserved Ejection Fraction and Obesity” (from the SUMMIT Trial Study Group) were presented at AHA Scientific Sessions 2024 with simultaneous publication in the New England Journal of Medicine. The purpose of this study was to test the effect of tirzepatide on major heart failure outcomes in patients with HFpEF and obesity.
This multi-national double-blind trial randomized 731 adults aged 40 or older with HFpEF (congestive heart failure with an EF ≥ 50%) and obesity (BMI ≥ 30 kgm2) to weekly injections of tirzepatide or placebo in a 1:1 fashion. Tirzepatide was up titrated to a maximum dose of 15mg/week as tolerated. The two primary end points were a composite of adjudicated death from cardiovascular causes or a worsening heart-failure event (assessed in a time-to-first-event analysis) and the change from baseline to 52 weeks in the Kansas City Cardiomyopathy Questionnaire (KCCQ) clinical summary score. The mean age was 65.2 years and the mean BMI was 38.3 kg/m2; 54% were women,
At a median of 2 years of follow up, tirzepatide was associated with a significantly lower risk of cardiovascular death or a worsening heart failure event compared to placebo (9.9% vs 15.3% respectively, HR 0.62 [95% CI 0.41-0.95]; p =0.026). This was driven primarily by a decrease in worsening heart failure events (8.0% vs 14.2%, HR 0.54 [0.34-0.85]) as there was no significant difference in cardiovascular mortality (2.2% vs 1.4%, HR 1.58 [0.52-4.83]). Patients in the tirzepatide group also experienced a significant improvement in KCCQ scores compared to placebo. About 4% of tirzepatide patients discontinued treatment due to gastrointestinal side effects.
Milton Packer, M.D., a distinguished scholar in cardiovascular science at Baylor University Medical Center in Dallas and a visiting professor at Imperial College in London, concluded: “These results indicate tirzepatide produced meaningful benefits for people living with heart failure with preserved ejection fraction and obesity. The patients experienced a lower combined risk of worsening heart failure events and cardiovascular disease death, along with improved health status and exercise tolerance. This is the first trial to demonstrate that a medication can change the clinical trajectory of the disease in patients with HFpEF and obesity.”