Tirzepatide improved symptoms, function and medication burden in HFpEF and obesity analysis
New detail on tirzepatide's effect on symptoms, walking distance and medication use matters to patients with this hard-to-treat form of heart failure, though approval for it has not been reported.
A detailed analysis of the SUMMIT trial published in the journal Circulation found that tirzepatide improved heart failure symptoms, exercise capacity and quality of life, and cut the number of heart failure medications patients needed, in people who have heart failure with preserved ejection fraction (HFpEF) and obesity. Tirzepatide is the molecule sold as Mounjaro and Zepbound [1].
SUMMIT, which stands for Study of Tirzepatide in Participants with Heart Failure With Preserved Ejection Fraction and Obesity, enrolled 731 patients with class II to IV heart failure, an ejection fraction of at least 50% and a body mass index of at least 30 kg/m2. Of them, 364 were assigned to tirzepatide, injected weekly and increased as tolerated to 15 mg, and 367 to placebo, both added to their usual heart failure treatment. Median follow-up was 104 weeks, with a maximum of 3.0 years [1].
At the start, patients averaged 65.2 years of age, 53.8% (393) were women, average BMI was 38.2, the average Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) was 53.5 and the average six-minute walk distance was 302.8 meters. Just over half — 53%, or 388 patients — had a worsening heart failure event in the previous 12 months [1].
The trial's two primary endpoints were the time to a first worsening heart failure event or cardiovascular death, and the change in KCCQ-CSS at 52 weeks [1]. In the expanded analysis, at 52 weeks tirzepatide increased KCCQ-CSS by 6.9 points compared with placebo (95% CI, 3.3 to 10.6), six-minute walk distance by 18.3 meters (95% CI, 9.9 to 26.7) and the EQ-5D-5L health state index by 0.06 (95% CI, 0.03 to 0.09). All three results had a P value below 0.001 [1].
Patients taking tirzepatide also shifted toward better scores on the Patient Global Impression of Severity for overall health (proportional odds ratio 1.99; 95% CI, 1.44 to 2.76) and toward a better New York Heart Association class (proportional odds ratio 2.26; 95% CI, 1.54 to 3.31), and they needed fewer heart failure medications (P=0.015) [1].
For heart failure events specifically, tirzepatide lowered the risk of worsening heart failure that required hospitalization or intravenous drugs in an urgent care setting, with a hazard ratio of 0.41 (95% CI, 0.22 to 0.75) [1]. Across several ways of defining the combined risk of death and worsening heart failure, hazard ratios ranged from 0.41 to 0.67 [1]. When all of the outcomes were ranked together — death first, then worsening heart failure, then the 52-week changes in KCCQ-CSS and six-minute walk distance — the win ratio was 1.63 (95% CI, 1.17 to 2.28; P=0.004), meaning the tirzepatide group had more favorable comparisons than the placebo group [1].
The journal published an accompanying editorial titled "Holistic View of Tirzepatide's Role in Obesity-Related HFpEF" [1].
Why it matters for patients
Obesity is one of the main drivers of HFpEF, and the condition tends to worsen as body mass index rises [1]. The article notes that none of the medications previously developed for HFpEF target obesity, and that, taken together, the benefits of those drugs on worsening heart failure events, health status and exercise capacity have generally been modest [1]. That leaves many patients with persistent symptoms and limits on daily activity.
The trial results describe how tirzepatide performed in one specific group: adults with class II to IV heart failure, an ejection fraction of at least 50%, a BMI of at least 30, and, in most cases, a heart failure flare in the prior year. Everyone was also already taking other heart failure therapy [1]. The researchers say the results may apply to a wide range of patients with HFpEF and obesity, including those without meaningfully elevated NT-proBNP before treatment [1].
Tirzepatide is not semaglutide; semaglutide is the molecule in Ozempic, Wegovy and Rybelsus, and this trial did not test it. What tirzepatide does to the risk of death on its own, how it compares with other HFpEF treatments, and how the drug's side effects and discontinuation rates played out in SUMMIT have not been reported in this analysis. Whether tirzepatide is approved for HFpEF has not been disclosed, and no cost or insurance-coverage information is included.
What happens next
SUMMIT's primary results were published earlier [1]. The article states that the trial data "may have important implications in the development of guidelines for the treatment of patients with heart failure with preserved ejection fraction and obesity," but no timeline for guideline review, regulatory filing or approval decision has been reported [1]. Under the trial's data-sharing terms, anonymized participant data can be requested six months after the studied indication is approved in the United States and European Union and after the primary publication is accepted, whichever comes later; no expiration date has been set [1]. The sponsor was Eli Lilly and Company, and the trial is registered as NCT04847557 [1].
Sources
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