Is the effect of dapagliflozin in patients with heart failure and reduced ejection fraction consistent in men and women?
In this prespecified subgroup analysis of a randomized clinical trial that included 4744 patients, dapagliflozin, as compared with placebo, increased the proportion of patients with an improvement in the Kansas City Cardiomyopathy Questionnaire total symptom score, clinical summary score, and overall summary score and decreased the proportion with a deterioration, irrespective of sex.
Dapagliflozin reduced the risk of worsening heart failure and death and improved symptoms, physical function, and health-related quality of life similarly in men and women with heart failure and reduced ejection fraction.
Women may respond differently to certain treatments for heart failure (HF) with reduced ejection fraction (HFrEF) than men.
To investigate the efficacy and safety of dapagliflozin compared with placebo in men and women with HFrEF enrolled in the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure trial (DAPA-HF).
Design, Setting, and Participants
Prespecified subgroup analysis of a phase 3 randomized clinical trial conducted at 410 sites in 20 countries. Patients with New York Heart Association functional class II through IV with an ejection fraction of 40% or less and elevated N-terminal pro-B-type natriuretic peptide were eligible. Data were analyzed between June 2020 and January 2021.
Addition of once-daily 10 mg of dapagliflozin or placebo to guideline-recommended therapy.
Main Outcomes and Measures
The primary outcome was the composite of an episode of worsening HF (HF hospitalization or urgent HF visit requiring intravenous therapy) or cardiovascular death.
A total of 4744 patients were randomized in DAPA-HF, of whom 1109 were women (23.4%). Compared with placebo, dapagliflozin reduced the risk of worsening HF events or cardiovascular death to a similar extent in both men and women (hazard ratios, 0.73 [95% CI, 0.63-0.85] and 0.79 [95% CI, 0.59-1.06], respectively; P for interaction = .67). Consistent benefits were observed for the components of the primary outcome and all-cause mortality. Compared with placebo, dapagliflozin increased the proportion of patients with a meaningful improvement in symptoms (Kansas City Cardiomyopathy Questionnaire 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 (Kansas City Cardiomyopathy Questionnaire total symptom score decrease of ≥5 points; men, 25% vs 34%; women, 27% vs 31%; P for interaction = .15), irrespective of sex. Results were consistent for the Kansas City Cardiomyopathy Questionnaire clinical summary score and overall summary score. Study drug discontinuation and serious adverse events were not more frequent in the dapagliflozin group than in the placebo group in either men or women.
Conclusions and Relevance
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. In addition, dapagliflozin was safe and well-tolerated irrespective of sex.
ClinicalTrials.gov Identifier: NCT03036124
Butt JH, Docherty KF, Petrie MC, et al. Efficacy and Safety of Dapagliflozin in Men and Women With Heart Failure With Reduced Ejection Fraction: A Prespecified Analysis of the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure Trial. JAMA Cardiol. Published online March 31, 2021. doi:10.1001/jamacardio.2021.0379
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