The SUMMIT trial, presented at the American Heart Association (AHA) Scientific Sessions 2024, reveals that tirzepatide (Zepbound/Mounjaro) significantly reduces the risk of worsening heart failure in patients with obesity and heart failure with preserved ejection fraction (HFpEF). The study, a multicenter, randomized, double-blind, placebo-controlled phase 3 trial, enrolled 731 adults with HFpEF and obesity across 10 countries.
Key Findings from the SUMMIT Trial
The trial demonstrated that tirzepatide was associated with a 38% reduction in the combined risk of heart failure hospitalization or cardiovascular death (HR, 0.62; 95% CI, 0.41 to 0.95; P = .026). Patients treated with tirzepatide also experienced a 12% to 21% reduction in body weight during the trial. The study's primary outcomes included the time-to-first occurrence of urgent heart failure visit, heart failure hospitalization, oral diuretic intensification, or cardiovascular death, and the change in the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) from baseline to week 52.
Impact on Heart Failure Events and Quality of Life
Further analysis indicated a 46% relative reduction in the risk of worsening heart failure events (HR, 0.54; 95% CI, 0.34 to 0.85) with tirzepatide. The KCCQ-CSS, a measure of health status, showed a significant improvement in the tirzepatide group, with a mean change of 19.5 (SD, 1.2) compared to 12.7 (SD, 1.3) in the placebo group (between-group difference, 6.9; 95% CI, 3.3 to 10.6; P < .001).
Safety Profile
Adverse events leading to discontinuation of the trial drug occurred in 6.3% of the tirzepatide group and 1.4% of the placebo group. Notably, adjudicated death from cardiovascular causes occurred in 2.2% of the tirzepatide group and 1.4% of the placebo group (HR, 1.58; 95% CI, 0.52 to 4.83).
Expert Commentary
"These results indicate tirzepatide produced meaningful benefits for people living with heart failure with preserved ejection fraction and obesity," said principal investigator Milton Packer, MD, from Baylor University Medical Center. "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."
Regulatory Submissions and Future Implications
Eli Lilly and Company has submitted tirzepatide for the treatment of HFpEF and obesity to the US FDA and the European Medicines Agency, with plans to submit to other regulatory agencies. Jeff Emmick, MD, PhD, senior vice president of product development at Eli Lilly and Company, stated, "The SUMMIT data suggest that, if approved, tirzepatide could provide a significant advancement for these patients, potentially setting a new standard of care."
