In a groundbreaking international trial called SUMMIT, tirzepatide, a dual GIP and GLP-1 receptor agonist, demonstrated a significant reduction in the combined risk of worsening heart failure events and cardiovascular death in obese adults with heart failure with preserved ejection fraction (HFpEF). The study, involving 731 participants across nine countries, marks the first successful trial evaluating a medication's impact on major heart failure outcomes in this specific patient population.
The findings, presented at the American Heart Association's Scientific Sessions 2024, revealed that participants taking tirzepatide experienced a 38% reduction in the combined risk of cardiovascular death or worsening heart failure events compared to those receiving a placebo. Specifically, worsening heart failure events occurred in 8.0% of the tirzepatide group compared to 14.2% in the placebo group, representing a 46% risk reduction.
Impact on Health Status and Function
Beyond reducing cardiovascular events, tirzepatide also significantly improved patients' overall health status and physical function. At one year, scores on the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) improved by an average of 6.9 points more in the tirzepatide group compared to the placebo group, indicating a perceived greater improvement in health and function. Additionally, participants in the tirzepatide group improved their six-minute walking distance by an average of 18.3 meters farther than the placebo group at one year.
Weight Loss and Inflammation Reduction
The study confirmed previous findings regarding tirzepatide's efficacy in weight management. Participants experienced a mean change in body weight of 11.9% greater weight loss in the tirzepatide group compared to the placebo group, measured at one year. Furthermore, tirzepatide demonstrated a reduction in systemic inflammation, as indicated by a 32.9% average difference in percent changes in high-sensitivity C-reactive protein (hs-CRP) levels compared to placebo.
Expert Commentary
"These results indicate tirzepatide produced meaningful benefits for people living with heart failure with preserved ejection fraction and obesity," said lead study author Milton Packer, M.D., 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."
Trial Design and Patient Population
The SUMMIT trial enrolled adults aged 40 years and older with a diagnosis of HFpEF and obesity (BMI ≥30 kg/m2). Participants were randomly assigned to receive either tirzepatide or placebo via weekly injections, with doses gradually increased from 2.5 mg to a maximum of 15 mg per week. The median follow-up duration was two years, with a maximum of three years.
Limitations and Future Directions
The study authors noted that the use of BMI as the sole measure of body size was a limitation, as some HFpEF patients may have a normal BMI but elevated waist-to-height ratios, indicating visceral adiposity. Further research is needed to identify the most accurate parameters for identifying patients who would benefit from tirzepatide treatment.
