Treatment with tirzepatide reduced the risk of cardiovascular (CV) death and worsening heart failure (HF) in patients with HF with preserved ejection fraction (HFpEF) and obesity, according to the SUMMIT trial presented at AHA 2024.

“Tirzepatide reduced the composite of CV death and worsening HF events by 38 percent (p=0.026), … which was statistically significant, achieving success on our primary endpoint,” said lead author Dr Milton Packer from Baylor University Medical Center in Dallas, Texas, US.

“Obesity contributes to worsening HF, and tirzepatide causes considerable weight loss [in patients with obesity. However], research is lacking on its effects on CV outcomes [in patients with obesity and HFpEF],” said Packer.

“SUMMIT is the first trial in patients with HFpEF and obesity, with major HF outcomes as the primary prespecified endpoint,” he noted.

This trial included 731 patients (mean age 65.2 years, 53.8 percent female) diagnosed with HFpEF and obesity with a mean BMI of 38.3 kg/m². Participants were randomized to receive either tirzepatide (n=364) or placebo (n=367) for 52 weeks. Tirzepatide was given at a starting dose of 2.5 mg once weekly, with the dose gradually increasing from 2.5 mg/week, as tolerated, to a target dose of 15 mg/week.

Over a median follow-up of 104 weeks, as assessed in a time-to-first event analysis, the primary composite endpoint of CV death and worsening HF only occurred in 9.9 percent of tirzepatide-treated patients compared with 15.3 percent of placebo-treated patients (5.5 vs 8.8 events per 100 patient-years). [AHA 2024, abstract 4171195]

Packer further stated that the result was mainly driven by a decreased risk of worsening HF events resulting in hospitalization (HR, 0.41; p=0.004) or use of urgent intravenous drug therapy (HR, 0.44; p=0.018).

Moreover, this benefit was paralleled by an improvement in health status, as shown by an increase in KCCQ-CSS* at 52 weeks, the study’s co-primary endpoint, among patients treated with tirzepatide compared with placebo (19.5 vs 12.7 points; between-group difference of 6.9; p<0.001).

Of note, the effect of tirzepatide on both primary outcomes of CV death or worsening HF and KCCQ-CSS appeared to be consistent across prespecified subgroups, Packer noted.

As for the key secondary endpoints, a significant increase in the 6-minute walk distance (between-group difference, 18.3 metres) and reduction in body weight (between-group difference, -11.6 percent) and high-sensitivity C-reactive protein level, a marker of systemic inflammation (between-group difference, -34.9 percent; p<0.001 for all) was observed at 52 weeks, all of which favoured tirzepatide over placebo.

“These results indicate that tirzepatide produced meaningful benefits for people living with HFpEF and obesity,” said Packer. “The patients experienced a lower combined risk of worsening HF events and CV 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.”

“The safety profile of tirzepatide in SUMMIT was consistent with prior tirzepatide clinical trials,” he added.

*KCCQ-CSS: Kansas City Cardiomyopathy Questionnaire-clinical summary score