In a subanalysis of the landmark DAPA-HF trial, dapagliflozin benefits were observed in both men and women, an important finding given variable response to cardiovascular drugs among women.
The sodium-glucose cotransporter-2 inhibitor dapagliflozin reduced the risk of worsening heart failure and death in both men and women with heart failure with reduced ejection fraction (HFrEF), according to results of a study published online today in JAMA Cardiology.
Dapagliflozin also improved symptoms, physical function, and health-related quality of life (HRQoL) in both sexes.
The study, a prespecified subgroup analysis of data from the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) trial, was conducted against existing evidence that women may respond differently to treatments for HFrEF than men, wrote the authors.
DAPA-HF was a phase 3 randomized clinical trial that evaluated the addition of once-daily dapagliflozin 10 mg vs placebo to guideline recommended therapy for HFrEF. The primary outcome was the composite of an episode of worsening HF (HF hospitalization or urgent HF visit requiring intravenous therapy) or cardiovascular (CV) death.
Of the 4744 patients randomized in DAPA-HF, 23.4% were women. The risk of worsening HF events or CV death was similarly reduced in men and women treated with dapagliflozin (hazard ratios, 0.73 [95% CI, 0.63-0.85] and 0.79 [95% CI, 0.59-1.06], respectively; P for interaction = .67) vs placebo. The benefit was consistent for the primary outcome and all-cause mortality.
Dapagliflozin increased the proportion of patients with a meaningful improvement in symptoms (Kansas City Cardiomyopathy Questionnaire [KCCQ] total symptom score of ≥5 points; men, 59% vs 50%; women, 57% vs 54%; P for interaction = .14) and decreased the proportion with worsening symptoms (KCCQ total symptom score decrease of ≥5 points; men, 25% vs 34%; women, 27% vs 31%; P for interaction = .15), regardless of sex. Results were consistent for the KCCQ clinical summary score and overall summary score.
Neither study drug discontinuation rates or serious adverse events were more frequent in the dapagliflozin vs placebo groups, in either men or women.
“The proportion of women in DAPA-HF was relatively low but similar to other global HFrEF trials,” wrote the authors, led by John J. V. McMurray, MD, of British Heart Foundation Cardiovascular Research Centre in Glasgow, Scotland. “Thus, women continue to be underrepresented in HF trials, and greater efforts should be made to increase the proportion of women in HF trials.”
In conclusion, the authors wrote, " Dapagliflozin reduced the risk of worsening HF, cardiovascular death, and all-cause death and improved symptoms, physical function, and health-related quality of life similarly in men and women with heart failure and reduced ejection fraction."
Dapagliflozin was approved by the US Food and Drug Administration (FDA) for the treatment of type 2 diabetes in 2014 and for patients with HFrEF with or without diabetes in May 2020.
Earlier this year, the FDA granted the drug Priority Review for the treatment of chronic kidney disease in patients with and without type 2 diabetes.