Physicians' Academy for Cardiovascular Education

SGLT2i reduces risk of worsening HF or CV death similarly in men and women with HFrEF

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

Literature - Butt JH, Docherty KF, Petrie MC et al. - JAMA Cardiol. 2021 Mar 31;e210379. doi: 10.1001/jamacardio.2021.0379.

Introduction and methods

The DAPA-HF trial showed that addition of dapagliflozin to conventional guideline-recommended therapies reduced the composite outcome of CV death and worsening HF events in patients with HFrEF with and without diabetes in comparison to placebo [1]. It is known that women may respond differently to certain HF medications compared to men [2-8]. This prespecified subgroup analysis of DAPA-HF investigated the efficacy and safety of dapagliflozin in men and women.

DAPA-HF was a randomized, double-blind, placebo-controlled trial that randomized 4744 patients with HFrEF (1109 were women, 23.4%) to receive either dapagliflozin (10 mg, once daily) or placebo in addition to guideline-recommended therapy. Included patients were aged ≥18 years, had NYHA class II trough IV, LVEF≤40%, were optimally treated with pharmacologic or device therapy for HF and had NT-proBNP ≥600 pg/mL (≥400 pg/mL if hospitalized for HF within the last 12 months; ≥900 pg/mL in case of AF). Patients with eGFR <30 mL/min/1.73m² or rapidly declining kidney function, symptomatic hypotension, SBP <95 mmHg or type 1 diabetes were excluded. The primary outcome was the composite of worsening HF events or CV death. Secondary outcomes included HF hospitalization or CV death (and each outcome separately); total HF hospitalizations or CV death; all-cause death; an extended primary outcome (composite of the primary endpoint plus worseling HF symptoms/signs leading to initiation of new oral treatment or augmentation of existing oral treatment); change from baseline to 8 months in the Kansas City Cardiomyopathy Questionnaire total symptom score (KCCQ-TSS); KCCQ overall summary score (KCCQ-OSS) and KCCQ clinical summary score (KCCQ-CSS). Follow-up was 24 months.

Main results


Dapagliflozin added to guideline-recommended therapy reduced the risk of the primary endpoint of worsening HF events or CV death to a similar extent in men and women, compared to placebo. Dapagliflozin increased the proportion of patients with a clinically meaningful improvement of ≥5 points in KCCQ-TSS and decreased the proportion of patients with a clinically important deterioration of ≥5 points in KCCQ-TSS compared with placebo in both men and women. SEA and study drug discontinuation were similar between treatment groups, irrespective of sex.


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Find this article online at JAMA Cardiol.

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