Treatment benefit from tirzepatide was consistent across multiple domains of heart failure (HF) severity and did not differ by sex, despite women exhibiting greater adiposity, symptom severity and poorer exercise capacity but lower left ventricular mass and paracardiac fat deposition when compared to men, according to a secondary analysis of the SUMMIT trial published July 10 in JACC: Heart Failure.

Barry A. Borlaug, MD, FACC, et al., included 731 patients (54% women) with NYHA functional class II-IV HF with preserved ejection fraction (HFpEF) and BMI ≥30 kg/m². Trial participants were randomized to tirzepatide or placebo, and primary outcomes were time to cardiovascular death or worsening HF and change in KCCQ-Clinical Summary Score (CSS) at 52 weeks. Their analysis explored sex differences in baseline characteristics and treatment effect.

Women had greater BMI, waist to height ratio, symptom severity and poorer exercise capacity, while men had greater left ventricular remodeling and paracardiac fat. In women, higher waist to height ratio was associated with poorer kidney function (interaction p=0.043). This relationship was not observed in men.

Despite these baseline differences, the effect of tirzepatide on the risk of worsening HF or cardiovascular death in women vs. men was similar (hazard ratio, 0.66 and 0.61, respectively, interaction p=0.81). In women vs. men, the authors also note no heterogeneity in effect on KCCQ-CSS (8.1- and 5.5-point placebo-corrected improvement, respectively, interaction p=0.43) or six-minute walking distance (16 m and 15 m placebo-corrected improvement, respectively, interaction p=0.76).

Among participants randomized to the treatment group, women had a stronger association between decreases in body weight and improvements in KCCQ-CSS when compared to men (interaction p=0.0058).

"These data provide new insight into sex differences in obesity-related HFpEF, emphasizing the greater evidence if excess body fat and adipose-related sequelae such as inflammation and exercise dysfunction in women," write the authors. "We also show that benefits from tirzepatide were not unique to one sex but applied to both equally."