Article Impact Level: HIGH Data Quality: STRONG Summary of New England Journal of Medicine, NEJMoa2410027. https://doi.org/10.1056/NEJMoa2410027 Dr. Milton Packer et al.
Points
- This double-masked, randomized trial evaluated tirzepatide’s effects on cardiovascular outcomes and quality of life in 731 patients with HFpEF and obesity over at least 52 weeks.
- Tirzepatide reduced the composite risk of cardiovascular death or worsening heart failure events (9.9% vs. 15.3% in placebo; HR 0.62; P=0.026), with a significant reduction in worsening heart failure events (8.0% vs. 14.2%; HR 0.54).
- Tirzepatide significantly improved Kansas City Cardiomyopathy Questionnaire scores (average increase of 19.5 vs. 12.7 points; P<0.001), reflecting better health status and quality of life.
- Adverse events, mainly gastrointestinal, led to drug discontinuation in 6.3% of tirzepatide patients compared to 1.4% of placebo patients.
- Tirzepatide effectively reduces cardiovascular risk and improves the quality of life in patients with HFpEF and obesity, although some adverse effects require consideration.
Summary
This double-masked, randomized, placebo-controlled trial evaluated the effects of tirzepatide, a dual GLP-1, and GIP receptor agonist, on cardiovascular outcomes in patients with heart failure with preserved ejection fraction (HFpEF) and obesity. A total of 731 patients with a body-mass index (BMI) of at least 30 and a left ventricular ejection fraction ≥50% were randomly assigned to receive either tirzepatide (up to 15 mg weekly) or placebo for at least 52 weeks. The primary endpoints were a composite of cardiovascular death or worsening heart failure events and the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS) change, which measures quality of life.
At the end of the 104-week follow-up period, the tirzepatide group showed a significantly lower rate of cardiovascular death or worsening heart failure events compared to the placebo group. Specifically, 9.9% of patients in the tirzepatide group experienced the composite event versus 15.3% in the placebo group (hazard ratio [HR], 0.62; 95% CI, 0.41–0.95; P=0.026). Worsening heart failure events occurred in 8.0% of the tirzepatide group compared to 14.2% in the placebo group (HR, 0.54; 95% CI, 0.34–0.85). Although cardiovascular death rates were slightly higher in the tirzepatide group (2.2% vs. 1.4%), this difference was not statistically significant (HR, 1.58; 95% CI, 0.52–4.83).
Tirzepatide also significantly improved health status as measured by the KCCQ-CSS, with an average change of 19.5 ± 1.2 points in the treatment group compared to 12.7 ± 1.3 points in the placebo group (between-group difference, 6.9; 95% CI, 3.3–10.6; P<0.001). Adverse events, primarily gastrointestinal, led to discontinuation of the drug in 6.3% of patients in the tirzepatide group versus 1.4% in the placebo group. These results suggest that tirzepatide reduces cardiovascular risk and improves the quality of life in patients with HFpEF and obesity.
Link to the article: https://www.nejm.org/doi/10.1056/NEJMoa2410027
References Packer, M., Zile, M. R., Kramer, C. M., Baum, S. J., Litwin, S. E., Menon, V., Ge, J., Weerakkody, G. J., Ou, Y., Bunck, M. C., Hurt, K. C., Murakami, M., & Borlaug, B. A. (2024). Tirzepatide for heart failure with preserved ejection fraction and obesity. New England Journal of Medicine, NEJMoa2410027. https://doi.org/10.1056/NEJMoa2410027
