AHA 2024 – Tirzepatide lowers the risk of worsening heart failure and CVD death for obese adults

Researchers from the SUMMIT trial have reported that treatment with tirzepatide has reduced the risk of worsening heart failure and cardiovascular disease-related  death for obese adults.

The findings were reported on Nov. 16, 2024 at the American Heart Association Scientific Sessions 2024.

“These results indicate tirzepatide produced meaningful benefits for people living with heart failure with preserved ejection fraction [HFpEF] and obesity,” said lead study author 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. Packer.

“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,” Packer added.

Tirzepatide is FDA-approved for the treatment of people with Type 2 diabetes or for chronic weight management in people with overweight or obesity.

Between April 20, 2021 and June 30, 2023, researchers screened 1,494 patients with heart failure and obesity at 129 health centers in nine countries.

They enrolled 731 adults ages 40 years and older. The mean age at enrollment was 65.2 years and 53.8% of the subjects were women. For the entire group, the mean BMI of 38.3 kg/m².

All subjects had ejection fraction ≥50%, and they were randomized to receive either tirzepatide or placebo, 364 in the tirzepatide group and 367 in the placebo group.

Median follow-up was 104 weeks. And 15 patients (2%) were lost to follow-up by the conclusion of the study, 4 in the tirzepatide group, 11 in the placebo group.

The subjects received a weekly injection of tirzepatide or placebo. The weekly dose was gradually increased from 2.5 mg to a maximum dose of 15 mg per week.

All subjects continued taking their regular medications including those for heart failure.

Every 1-6 months, the investigators monitored body weight, heart failure symptoms, major worsening heart failure events, changes in heart failure medications and adverse events.

The investigators reported that cardiovascular death or worsening heart failure events occurred in 36 subjects (9.9%) in the tirzepatide group and 56 subjects (15.3%) in the placebo group. This was a 38% reduction in risk among those treated with tirzepatide.

Worsening heart failure events appeared in 29 subjects (8.0%) in the tirzepatide group compared to 52 (14.2%) in the placebo group. This was a 46% reduction in risk for those treated with tirzepatide.

The researchers reported 15 cardiovascular deaths among both groups. Eleven were not preceded by worsening heart failure. Two in the tirzepatide group occurred after subjects had not taken the medication for more than 15 months.

For all subjects, there were 34 deaths for any reason.

At one year, the KCCQ-CSS 9 Kansas City Cardiomyopathy Questionnaire Clinical Summary Score) improved by an average of 6.9 points more in the tirzepatide group than the placebo group, suggesting greater improvement in physical function, quality of life and social function with heart failure among the tirzepatide subjects.

At one year, tirzepatide subjects achieved an 11.9% greater mean change in body weight compared to placebo subjects

Thet also achieved improvement in their six-minute walking distance test at one year by an average of 18.3 meters farther then the placebo group.

Subjects in the tirzepatide group also achieved less systemic inflammation, as indicated by a high-sensitivity C-reactive protein (hs-CRP) measure. The difference  between the groups was 32.9%, indicating lower levels of inflammation for the tirzepatide group.

“These results indicate tirzepatide produced meaningful benefits for people living with heart failure with preserved ejection fraction and obesity,” said Packer. “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.”