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The following is a summary of “Tirzepatide for Heart Failure with Preserved Ejection Fraction and Obesity,” published in the November 2024 issue of Endocrinology by Packer et al.  

Obesity increases the risk of heart failure with preserved ejection fraction (HFpEF). Tirzepatide, a dual receptor agonist of the glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) helps in weight loss, but its effects on cardiovascular outcomes are unclear.  

Researchers conducted a prospective study to evaluate the effects of tirzepatide on cardiovascular outcomes in people with HFpEF and obesity.  

They assigned 731 participants with HF (ejection fraction ≥50%) and a body-mass index (BMI) ≥30 to receive tirzepatide (up to 15 mg subcutaneously once per week) or placebo for at least 52 weeks. The primary outcomes included cardiovascular death or worsening HF and changes in the Kansas City Cardiomyopathy Questionnaire (KCCQ) clinical summary score.  

The results showed that the composite of cardiovascular death or worsening HF occurred in 36 participants (9.9%) in the tirzepatide group and 56 participants (15.3%) in the placebo group (HR, 0.62; 95% CI, 0.41 to 0.95; P=0.026). Worsening HF events occurred in 29 participants (8.0%) in the tirzepatide group and 52 participants (14.2%) in the placebo group (HR, 0.54; 95% CI, 0.34 to 0.85), while cardiovascular death occurred in 8 participants (2.2%) and 5 participants (1.4%), respectively (HR, 1.58; 95% CI, 0.52 to 4.83). At 52 weeks, the mean change in the KCCQ clinical summary score was 19.5±1.2 for the tirzepatide group compared to 12.7±1.3 for the placebo group (between-group difference, 6.9; 95% CI, 3.3 to 10.6; P<0.001), AEs led to discontinuation of the drug in 6.3% of participants in the tirzepatide group and 1.4% in the placebo group.  

They concluded that tirzepatide reduced cardiovascular events and improved health status in people with HFpEF and obesity.  

Source: nejm.org/doi/full/10.1056/NEJMoa2410027