Abstract
Aims: We examined the efficacy and safety of dapagliflozin, compared with placebo, according to aetiology in patients with heart failure (HF) with reduced ejection fraction (HFrEF) enrolled in the Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure trial (DAPA-HF). Methods and results: Aetiology was investigator-reported and categorized as ischaemic or non-ischaemic. The primary outcome was the composite of an episode of worsening HF or cardiovascular death. A total of 4744 patients were randomized in DAPA-HF, of whom 2674 (56.4%) patients had an ischaemic aetiology. Participants with an ischaemic aetiology had a higher risk of cardiovascular mortality [hazard ratio (HR) 1.35, 95% confidence interval (CI) 1.13–1.63], but lower risk of HF hospitalization (HR 0.83, 95% CI 0.70–0.98) than non-ischaemic patients. Compared with placebo, dapagliflozin reduced the risk of worsening HF or cardiovascular death to a similar extent in both patients with ischaemic and non-ischaemic aetiology (HR 0.77, 95% CI 0.65–0.92, and HR 0.71, 95% CI 0.58–0.87, respectively; P for interaction = 0.55). Consistent benefits were observed for the components of the primary outcome and all-cause mortality. Dapagliflozin, as compared with placebo, increased the proportion of patients with an improvement of Kansas City Cardiomyopathy Questionnaire total symptom score (KCCQ-TSS) of ≥5 points (P for interaction = 0.32) and decreased the proportion with a deterioration in KCCQ-TSS of ≥5 points (P for interaction = 0.76), irrespective of aetiology. Study drug discontinuation and serious adverse events were similar according to treatment groups, irrespective of aetiology. Conclusions: Dapagliflozin reduced the risk of worsening HF and death, and improved symptoms, similarly in patients with ischaemic and non-ischaemic aetiology. In addition, dapagliflozin was safe and well-tolerated, irrespective of aetiology.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | European Journal of Heart Failure |
| Vol/bind | 23 |
| Udgave nummer | 4 |
| Sider (fra-til) | 601-613 |
| Antal sider | 13 |
| ISSN | 1388-9842 |
| DOI | |
| Status | Udgivet - 2021 |
Bibliografisk note
Funding Information:The DAPA-HF trial was funded by AstraZeneca. Prof. McMurray is supported by British Heart Foundation Centre of Research Excellence Grant RE/18/6/34217. Conflict of interest: Dr. Docherty reported personal fees from AstraZeneca and the University of Glasgow during the conduct of the study and personal fees from Eli Lilly outside the submitted work. Dr. Nicolau reported receiving grants from AstraZeneca during the conduct of the study and personal fees from Amgen, Daiichi-Sankyo, and Servier, grants from AstraZeneca, Bristol-Myers-Squibb, CLS Behring, Dalcor, Jansen, Novo Nordisk, and Vifor, and grants and personal fees from Bayer, Novartis, and Sanofi. Dr. Verma received grant support, lecture fees, and advisory board fees from AstraZeneca, Boehringer Ingelheim, Bayer, Janssen, and Merck, lecture fees from Sun Pharmaceutical Industries and EOCI Pharmacomm, grant support and advisory board fees from Amgen, and lecture fees and advisory board fees from Sanofi and Eli Lilly. Dr. Petrie reported grants from AstraZeneca during the conduct of the study; grants from Boehringer Ingelheim, Novo Nordisk, Novartis, and SQ Innovations and personal fees from Boehringer Ingelheim, Takeda, and Bayer outside the submitted work. Dr. Inzucchi reports personal fees and non-financial support from AstraZeneca, Boehringer Ingelheim, Sanofi/Lexicon, Merck, VTV Therapeutics, and Abbott/Alere, as well as personal fees from AstraZeneca and Zafgen.
Publisher Copyright:
© 2021 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.