An analysis of the landmark EMPEROR-Preserved trial is providing new insights into the effects of the SGLT2 inhibitor on heart failure outcomes based on patient sex in heart failure with preserved ejection fraction (HFpEF).
With women representing 44.7% of the enrolled population in the phase 3 trial, investigators determined empagliflozin contributed to a similar degree of risk reduction for cardiovascular death or hospitalization for heart failure among female patients as was seen in their male counterparts, with these results consistent for the primary outcome, KCCQ-CSS, and other secondary outcomes.
“Sex did not influence the effect of empagliflozin on reducing the risk of cardiovascular death or HF hospitalization or on health status as assessed by KCCQ scores, and there was no significant treatment–by–sex–by–fraction interaction on the primary endpoints. These findings stand in contrast to the striking influence of sex on the response to neprilysin inhibition,” wrote investigators.
With women representing the majority of HFpEF patients in contemporary settings, an international team of investigators led by Stefan Anker, MD, PhD, with the specific intent of assessing the specific influence of sex on the effects of empagliflozin among patients with HFpEF. To do so, investigators designed their analysis using patient data from the EMPEROR-Preserved trial to estimate effects of empagliflozin on the study’s primary and secondary outcomes, with subgroup analyses planned to further estimate effects based on baseline ejection fraction.
EMPEROR-Preserved randomized 5988 patients to either 10 mg empagliflozin or placebo therapy. With a median follow-up of 26.2 months, results indicated a total of 926 primary outcome events among the overall study cohort, including 415 among 2997 patients randomized to empagliflozin and 511 among 2991 patients randomized to placebo therapy (HR, 0.79; 95% CI, 0.69-0.90; P <.001).
In the present analysis, initial results indicated women in the placebo arm tended to have a lower risk for adverse outcomes, including a lower risk of all-cause mortality (HR, 0.69 [95% CI, 0.56-0.84]). For the primary composite outcome, use of empagliflozin was associated with a similar degree of risk reduction for cardiovascular death or hospitalization for heart failure in both men (HR, 0.81 [95% CI, 0.69-0.96]) and women (HR, 0.75 [95% CI, 0.61-0.92]) (P for interaction=.54). Further analysis indicated sex did not modify the relationship between empagliflozin and outcomes based on baseline ejection fraction.
Additionally, investigators pointed out similar trends were observed for secondary outcomes and physiological measures. When assessing KCCQ scores, results suggested empagliflozin was associated with similar improvements in the KCCQ-CSS (men: 1.38 vs women: 1.63; P for interaction=.77) at 52 weeks, as well as for KCCQ-OS and KCCQ-TSS.
“Because the clinical benefits of empagliflozin in patients with HFpEF are consistent in both women and men, the decision about the use of empagliflozin in patients with HFpEF should be made independently of the patient’s sex,” investigators added.
This study, “Effects of Empagliflozin in Women and Men with Heart Failure and Preserved Ejection Fraction,” was published in Circulation.