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Sex Differences With Dapagliflozin in DAPA-HF and DELIVER Trials
Quick Takes
- Both women and men derived similar benefits from dapagliflozin across the full spectrum of EF in HF.
- Dapagliflozin reduced the primary composite outcome of CV death or a worsening HF event, its components, all-cause death, and total events, as well as improved KCCQ scores, similarly in men and women.
- These findings are consistent with other SGLT2 inhibitors, suggesting a class effect for these drugs.
Study Questions:
What is the impact of sex on the efficacy and safety of dapagliflozin?
Methods:
The investigators compared clinical outcomes by sex (including the composite of cardiovascular [CV] death or worsening heart failure [HF] events; CV death; all-cause death, total events [first and recurrent HF hospitalization and CV death], and Kansas City Cardiomyopathy Questionnaire [KCCQ] scores) across the spectrum of left ventricular ejection fraction (EF) in a prespecified patient-level pooled analysis of DAPA-HF and DELIVER trials. The authors used Cox models to compare outcomes in women and men. Treatment effects for time-to-event outcomes were analyzed using Kaplan-Meier estimates and Cox proportional hazards models, stratified by diabetes status and trials. Total events were analyzed using Lin-Wei-Yang-Ying model.
Results:
Of a total of 11,007 randomized patients, 3,856 (35%) were women. Women with HF were older, had higher body mass index, but were less likely to have a history of diabetes and myocardial infarction/stroke; and more likely to have hypertension and atrial fibrillation, compared to men. At baseline, women had higher EF but worse KCCQ scores than men. After adjusting for baseline differences, women were less likely than men to experience CV death (adjusted hazard ratio [aHR], 0.69; 95% confidence interval [CI], 0.60-0.79), all-cause death (aHR, 0.69; 95% CI, 0.62-0.78), HF hospitalizations (aHR, 0.82; 95% CI, 0.72-0.94), and total events (adjusted rate ratio, 0.77; 95% CI, 0.71-0.84). Dapagliflozin reduced the primary endpoint in both men and women similarly (p-interaction = 0.77) with no sex-related differences in secondary outcomes (all p-interactions > 0.35) or safety events. The benefit of dapagliflozin was observed across the entire EF spectrum and was not modified by sex (p-interaction > 0.40). There were no sex-related differences in serious adverse events, adverse events, or drug discontinuation due to adverse events.
Conclusions:
The authors concluded that sex did not modify the treatment effect of dapagliflozin across the range of EF.
Perspective:
This patient-level pooled meta-analysis of DAPA-HF and DELIVER trials reports that both women and men derived similar benefits from dapagliflozin across the full spectrum of EF in HF. Specifically, dapagliflozin reduced the primary composite outcome of CV death or a worsening HF event, its components, all-cause death, and total events, as well as improved KCCQ scores, similarly in men and women. Furthermore, the safety profile of dapagliflozin compared with placebo was also similar in men and women in these two trials. Finally, these findings are consistent with other sodium-glucose co-transporter-2 (SGLT2) inhibitors, suggesting a class effect for these drugs.
Clinical Topics: Arrhythmias and Clinical EP, Diabetes and Cardiometabolic Disease, Heart Failure and Cardiomyopathies, Prevention, Atrial Fibrillation/Supraventricular Arrhythmias, Acute Heart Failure, Hypertension
Keywords: Atrial Fibrillation, Body Mass Index, Cardiomyopathies, Diabetes Mellitus, Heart Failure, Hypertension, Metabolic Syndrome, Myocardial Infarction, Primary Prevention, Sex Characteristics, Sodium-Glucose Transporter 2 Inhibitors, Stroke Volume, Ventricular Function, Left
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