Dapagliflozin and atrial fibrillation in heart failure with reduced ejection fraction: insights from DAPA-HF
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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Aims: Among patients with heart failure (HF) and reduced ejection fraction (HFrEF), those with atrial fibrillation (AF) may respond differently to certain treatments than patients without AF. We investigated the efficacy and safety of dapagliflozin in patients with HFrEF with and without AF in the Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure trial (DAPA-HF). We also examined the effect of dapagliflozin on new-onset AF. Methods and results: The primary outcome was the composite of an episode of worsening HF (HF hospitalization or urgent HF visit requiring intravenous therapy) or cardiovascular death. Of the 4744 patients randomized, 1910 (40.3%) had ‘any AF’ (history of AF or AF on enrolment electrocardiogram). Compared with placebo, dapagliflozin reduced the risk of worsening HF or cardiovascular death to a similar extent in patients with and without any AF [hazard ratio (HR) 0.75, 95% confidence interval (CI) 0.62–0.92 and 0.74, 95% CI 0.62–0.88, respectively; p for interaction = 0.88]. Consistent benefits were observed for the components of the primary outcome, all-cause mortality, and improvement of Kansas City Cardiomyopathy Questionnaire total symptom score. Among patients without AF at baseline, dapagliflozin did not significantly reduce the risk of new-onset AF compared with placebo (HR 0.86, 95% CI 0.60–1.22). However, patients with new-onset AF had a 5 to 6-fold higher risk of adverse outcomes when compared to those without incident AF. Conclusions: Dapagliflozin, compared with placebo, reduced the risk of worsening HF events, cardiovascular death, and all-cause death, and improved symptoms, in patients with and without AF. Dapagliflozin did not reduce the risk of new-onset AF.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | European Journal of Heart Failure |
| Vol/bind | 24 |
| Udgave nummer | 3 |
| Sider (fra-til) | 513-525 |
| Antal sider | 13 |
| ISSN | 1388-9842 |
| DOI | |
| Status | Udgivet - 2022 |
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: J.H.B. reports advisory board honoraria from Bayer, outside the submitted work. K.F.D. reports compensation from AstraZeneca for other services. P.S.J. reports compensation for consultant services from Novo Nordisk AS, Novartis, AstraZeneca and Boehringer Ingelheim. R.A.d.B. reports grants from Cardior Pharmaceuticals GmbH to other; compensation for other services from Novartis, AstraZeneca, Roche Diagnostics GmbH, Bayer, Abbott Fund; grants from AstraZeneca, Ionis Pharmaceuticals, Inc., Roche Diagnostics GmbH, Boehringer Ingelheim, Novo Nordisk and Abbott Fund to other. M.B. received personal fees from Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Servier, Medtronic, Vifor, and Novartis. A.S.D. reports receiving personal fees from Abbott, Biofourmis, Boston Scientific, Boehringer Ingelheim, Merck, Regeneron, and Relypsa and grants and personal fees from AstraZeneca, Alnylam, and Novartis. J.G.H. reports receiving grants and personal fees from AstraZeneca Canada and Boerhinger Ingelheim/Eli Lilly during the conduct of the study and grants and personal fees from Servier Canada, Novartis, Pfizer, and Bayer; personal fees from Otsuka, Alnylam, and Akcea; grants from Medtronic; and serving on the medical advisory board for Caridiol outside the submitted work. S.E.I. reports compensation for consultant services from Merck, Lexicon Pharmaceuticals, Inc., AstraZeneca, Boehringer Ingelheim, Abbott Diabetes Care, VTV Therapeutics, Novo Nordisk, Esperion; travel support from Novo Nordisk, Boehringer Ingelheim, AstraZeneca; compensation for other services from AstraZeneca, Boehringer Ingelheim. M.N.K. reports compensation for consultant services from Novo Nordisk, Applied Therapeutics, Janssen Global Services, LLC, AstraZeneca, Eli Lilly and Company, Merck, Bayer, Amgen, Sanofi US Services Inc, Boehringer Ingelheim, Vifor Pharma; grants from Boehringer Ingelheim, AstraZeneca. F.A.M. reports personal fees from AstraZeneca. J.C.N. reports 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. M.C.P. reports compensation for endpoint review committee services from Bayer, Boehringer Ingelheim, Takeda California, Inc, Novo Nordisk; compensation for consultant services from Boehringer Ingelheim, AstraZeneca, Novo Nordisk, Novartis, SQ Innovation; grants from Boehringer Ingelheim, Novartis, SQ Innovation and AstraZeneca to other. P.P. reports compensation for consultant services from AstraZeneca, Boehringer Ingelheim, Servier, Amgen, Vifor Pharma; compensation for other services from AstraZeneca, Pfizer, Novartis, Abbott Vascular. O.B. reports employment by AstraZeneca AB. A.M.L. reports stock holdings in AstraZeneca and employment by AstraZeneca. M. Sj?strand reports employment by AstraZeneca. S.D.S. reports compensation for consultant services from GlaxoSmithKline, Arena, Novartis, Quantum Genomics, Bayer, Bristol-Myers Squibb, Cardior, Cytokinetics, Sarepta Therapeutics, Action Medical Research, Tremeau, Theracos, Moderna, Akros, Amgen, Boehringer Ingelheim, Alnylam Pharmaceuticals, Roche Diagnostics Corporation, American Regent, AstraZeneca, Cardurion, Merck, Daiichi Sankyo, Myokardia, Sanofi Pasteur Inc, Abbott Vascular, Eli Lilly and Company, Johnson and Johnson, CellProThera, Tenaya, Cardiac Dimensions; grants from Theracos, Celladon Corporation, Bristol-Myers Squibb, GlaxoSmithKline, Amgen, Respicardia, Inc, Novo Nordisk, Bayer, AstraZeneca, Mesoblast, Myokardia, Actelion Pharmaceuticals, Alnylam Pharmaceuticals, Bellepheron, Ionis, Sanofi Pasteur Inc, Neurotronik, Cytokinetics, Eli Lilly and Company, Novartis, Eidos; stock options in Dinaqor; travel support from Corvia. M.S.S. reports research grant support through Brigham and Women's Hospital from: Abbott, Amgen, Anthos Therapeutics, AstraZeneca, Bayer, Daiichi-Sankyo, Eisai, Intarcia, IONIS, Medicines Company, MedImmune, Merck, Novartis, Pfizer, Quark Pharmaceuticals; and consulting for Althera, Amgen, Anthos Therapeutics, AstraZeneca, Bristol-Myers Squibb, CVS Caremark, DalCor, Dr. Reddy's Laboratories, Fibrogen, IFM Therapeutics, Intarcia, MedImmune, Merck, Moderna, Novo Nordisk. J.J.V.McM. reports grants from AstraZeneca. L.K. reports compensation for other services from Novartis, Novo Nordisk, AstraZeneca.
Funding Information:
: J.H.B. reports advisory board honoraria from Bayer, outside the submitted work. K.F.D. reports compensation from AstraZeneca for other services. P.S.J. reports compensation for consultant services from Novo Nordisk AS, Novartis, AstraZeneca and Boehringer Ingelheim. R.A.d.B. reports grants from Cardior Pharmaceuticals GmbH to other; compensation for other services from Novartis, AstraZeneca, Roche Diagnostics GmbH, Bayer, Abbott Fund; grants from AstraZeneca, Ionis Pharmaceuticals, Inc., Roche Diagnostics GmbH, Boehringer Ingelheim, Novo Nordisk and Abbott Fund to other. M.B. received personal fees from Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Servier, Medtronic, Vifor, and Novartis. A.S.D. reports receiving personal fees from Abbott, Biofourmis, Boston Scientific, Boehringer Ingelheim, Merck, Regeneron, and Relypsa and grants and personal fees from AstraZeneca, Alnylam, and Novartis. J.G.H. reports receiving grants and personal fees from AstraZeneca Canada and Boerhinger Ingelheim/Eli Lilly during the conduct of the study and grants and personal fees from Servier Canada, Novartis, Pfizer, and Bayer; personal fees from Otsuka, Alnylam, and Akcea; grants from Medtronic; and serving on the medical advisory board for Caridiol outside the submitted work. S.E.I. reports compensation for consultant services from Merck, Lexicon Pharmaceuticals, Inc., AstraZeneca, Boehringer Ingelheim, Abbott Diabetes Care, VTV Therapeutics, Novo Nordisk, Esperion; travel support from Novo Nordisk, Boehringer Ingelheim, AstraZeneca; compensation for other services from AstraZeneca, Boehringer Ingelheim. M.N.K. reports compensation for consultant services from Novo Nordisk, Applied Therapeutics, Janssen Global Services, LLC, AstraZeneca, Eli Lilly and Company, Merck, Bayer, Amgen, Sanofi US Services Inc, Boehringer Ingelheim, Vifor Pharma; grants from Boehringer Ingelheim, AstraZeneca. F.A.M. reports personal fees from AstraZeneca. J.C.N. reports 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. M.C.P. reports compensation for endpoint review committee services from Bayer, Boehringer Ingelheim, Takeda California, Inc, Novo Nordisk; compensation for consultant services from Boehringer Ingelheim, AstraZeneca, Novo Nordisk, Novartis, SQ Innovation; grants from Boehringer Ingelheim, Novartis, SQ Innovation and AstraZeneca to other. P.P. reports compensation for consultant services from AstraZeneca, Boehringer Ingelheim, Servier, Amgen, Vifor Pharma; compensation for other services from AstraZeneca, Pfizer, Novartis, Abbott Vascular. O.B. reports employment by AstraZeneca AB. A.M.L. reports stock holdings in AstraZeneca and employment by AstraZeneca. M. Sjöstrand reports employment by AstraZeneca. S.D.S. reports compensation for consultant services from GlaxoSmithKline, Arena, Novartis, Quantum Genomics, Bayer, Bristol‐Myers Squibb, Cardior, Cytokinetics, Sarepta Therapeutics, Action Medical Research, Tremeau, Theracos, Moderna, Akros, Amgen, Boehringer Ingelheim, Alnylam Pharmaceuticals, Roche Diagnostics Corporation, American Regent, AstraZeneca, Cardurion, Merck, Daiichi Sankyo, Myokardia, Sanofi Pasteur Inc, Abbott Vascular, Eli Lilly and Company, Johnson and Johnson, CellProThera, Tenaya, Cardiac Dimensions; grants from Theracos, Celladon Corporation, Bristol‐Myers Squibb, GlaxoSmithKline, Amgen, Respicardia, Inc, Novo Nordisk, Bayer, AstraZeneca, Mesoblast, Myokardia, Actelion Pharmaceuticals, Alnylam Pharmaceuticals, Bellepheron, Ionis, Sanofi Pasteur Inc, Neurotronik, Cytokinetics, Eli Lilly and Company, Novartis, Eidos; stock options in Dinaqor; travel support from Corvia. M.S.S. reports research grant support through Brigham and Women's Hospital from: Abbott, Amgen, Anthos Therapeutics, AstraZeneca, Bayer, Daiichi‐Sankyo, Eisai, Intarcia, IONIS, Medicines Company, MedImmune, Merck, Novartis, Pfizer, Quark Pharmaceuticals; and consulting for Althera, Amgen, Anthos Therapeutics, AstraZeneca, Bristol‐Myers Squibb, CVS Caremark, DalCor, Dr. Reddy's Laboratories, Fibrogen, IFM Therapeutics, Intarcia, MedImmune, Merck, Moderna, Novo Nordisk. J.J.V.McM. reports grants from AstraZeneca. L.K. reports compensation for other services from Novartis, Novo Nordisk, AstraZeneca. . Conflict of interest
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.
Publisher Copyright:
© 2021 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.
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