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RCT: Tirzepatide Reduces Heart Failure Events and Improves Health Status in Obese HFpEF Patients

16 Nov, 2024 | 16:42h | UTC

Background: Obesity significantly increases the risk of heart failure with preserved ejection fraction (HFpEF) due to visceral adiposity-induced systemic inflammation affecting the myocardium. Tirzepatide, a dual agonist of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, induces substantial weight loss. However, its effects on cardiovascular outcomes in obese HFpEF patients were previously unknown.

Objective: To assess the impact of tirzepatide on cardiovascular events and health status in patients with HFpEF and obesity.

Methods: In this international, double-blind, randomized, placebo-controlled trial, 731 patients with HFpEF (ejection fraction ≥50%), a body-mass index (BMI) of at least 30, and New York Heart Association class II–IV symptoms were assigned to receive tirzepatide (up to 15 mg subcutaneously once weekly) or placebo for at least 52 weeks. The two primary endpoints were the composite of adjudicated death from cardiovascular causes or worsening heart-failure events, and the change from baseline to 52 weeks in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS).

Results: Over a median follow-up of 104 weeks, death from cardiovascular causes or worsening heart-failure events occurred in 9.9% of patients in the tirzepatide group versus 15.3% in the placebo group (hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.41 to 0.95; P=0.026). Worsening heart-failure events occurred in 8.0% with tirzepatide versus 14.2% with placebo (HR, 0.54; 95% CI, 0.34 to 0.85). At 52 weeks, the mean increase in KCCQ-CSS was 19.5 points in the tirzepatide group compared to 12.7 points in the placebo group (between-group difference, 6.9; 95% CI, 3.3 to 10.6; P<0.001). Adverse events leading to discontinuation occurred in 6.3% of tirzepatide patients versus 1.4% of placebo patients, mainly due to gastrointestinal symptoms.

Conclusions: Tirzepatide significantly reduced the risk of cardiovascular death or worsening heart failure and improved health status in patients with HFpEF and obesity.

Implications for Practice: These findings suggest that tirzepatide may be an effective therapeutic option for reducing heart failure events and enhancing quality of life in obese patients with HFpEF. Its benefits may be attributed to significant weight loss and anti-inflammatory effects, offering a potential new approach in managing this patient population.

Study Strengths and Limitations: Strengths include the randomized, double-blind design and a long median follow-up of 104 weeks. Limitations involve the exclusion of patients with BMI less than 30, which may limit applicability to non-obese HFpEF patients with increased visceral adiposity. Additionally, the higher rate of gastrointestinal adverse events leading to discontinuation in the tirzepatide group warrants cautious consideration.

Future Research: Further studies are needed to evaluate tirzepatide’s effects in HFpEF patients with lower BMI but increased visceral adiposity and to elucidate the mechanisms underlying its cardiovascular benefits.

Reference: Packer M, Zile MR, Kramer CM, Baum SJ, Litwin SE, Menon V, Ge J, et al. Tirzepatide for Heart Failure with Preserved Ejection Fraction and Obesity. New England Journal of Medicine. Published November 16, 2024. DOI: http://doi.org/10.1056/NEJMoa2410027

 


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