Effect of Dapagliflozin, Compared With Placebo, According to Baseline Risk in DAPA-HF
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Objectives: The authors sought to examine the effect of dapagliflozin across the spectrum of risk in patients enrolled in DAPA-HF. Background: In the DAPA-HF (Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure) trial, the sodium-glucose cotransporter 2 inhibitor dapagliflozin decreased the risk of worsening HF events and cardiovascular death in patients with HF and reduced ejection fraction. Methods: The MAGGIC (Meta-analysis Global Group in Chronic Heart Failure) and the PARADIGM-HF (Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure) PREDICT-HF (Risk of Events and Death in the Contemporary Treatment of Heart Failure) risk models were used to categorize patients according to risk score quintiles. The authors analyzed rates of the primary composite outcome of a worsening HF event or cardiovascular death, its components, and all-cause mortality according to risk quintile and whether risk modified the effect of dapagliflozin. Results: The MAGGIC score was available for 4,740 of 4,744 patients in DAPA-HF (median score 22 [IQR: 18–25]). A1-point increase was associated with an 8.2% (95% CI: 6.9%–9.4%) higher relative risk of the primary endpoint (P < 0.001). The benefit of dapagliflozin over placebo for the primary endpoint was similar across the spectrum of MAGGIC risk score (interaction P = 0.71). Applying the overall relative risk reduction (26%) with dapagliflozin added to standard therapy resulted in 7 fewer patients in the highest MAGGIC risk quintile experiencing a primary outcome, compared with 2 in the lowest quintile, per 100 person-years of treatment. The findings with PREDICT-HF were similar, although this model led to better risk discrimination. Conclusions: The benefits of dapagliflozin were consistent across the broad spectrum of baseline risk in DAPA-HF.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | JACC: Heart Failure |
| Vol/bind | 10 |
| Udgave nummer | 2 |
| Sider (fra-til) | 104-118 |
| ISSN | 2213-1779 |
| DOI | |
| Status | Udgivet - 2022 |
Bibliografisk note
Funding Information:
DAPA-HF ( NCT03036124 ) was funded by AstraZeneca. J.J.V.M. is supported by a British Heart Foundation Centre of Research Excellence Grant (RE/18/6/34217). Dr Docherty’s employer (University of Glasgow) has been remunerated by AstraZeneca for involvement in the DAPA-HF trial; and has received speaker’s fees from AstraZeneca and Eli Lilly. Dr Jhund’s employer (University of Glasgow) has been remunerated by AstraZeneca for involvement in the DAPA-HF and DELIVER trials; and has received speakers and advisory board fees from Novartis and advisory board fees and grants from Boehringer Ingelheim. Dr Inzucchi has received personal fees and nonfinancial support from AstraZeneca, Boehringer Ingelheim, Sanofi/Lexicon, Merck, VTV Therapeutics, and Abbott/Alere, and personal fees from AstraZeneca and Zafgen. Dr Køber has received financial support from AstraZeneca and personal fees from Novartis and Bristol Myers Squibb as a speaker. Dr Kosiborod has received personal fees from AstraZeneca and Vifor Pharma; grants, personal fees, and other from AstraZeneca; grants and personal fees from Boehringer Ingelheim; and personal fees from Sanofi, Amgen, NovoNordisk, Merck (Diabetes), Janssen, Bayer, Applied Therapeutics, and Eli Lilly. Dr Martinez has received personal fees from AstraZeneca. Dr Ponikowski has received personal fees and other from AstraZeneca, Boehringer Ingelheim, Bayer, Bristol Myers Squibb, Cibiem, Novartis, and RenalGuard; personal fees from Pfizer, Servier, Respicardia, Berlin-Chemie, and Amgen; and grants, personal fees, and other from Vifor Pharma. Dr Sabatine has received grants from Bayer, Daiichi-Sankyo, Eisai, GlaxoSmithKline, Pfizer, Poxel, Quark Pharmaceuticals, and Takeda; grants and personal fees from Amgen, AstraZeneca, Intarcia, Janssen Research and Development, The Medicines Company, MedImmune, Merck, and Novartis; and personal fees from Anthos Therapeutics, Bristol Myers Squibb, CVS Caremark, Dal-Cor, Dyrnamix, Esperion, IFM Therapeutics, and Ionis. Dr Sabatine is a member of the TIMI Study Group, which has also received institutional research grant support through Brigham and Women’s Hospital from Abbott, Aralez, Roche, and Zora Biosciences. Drs. Lindholm, Bengtsson, Sjöstrand, and Langkilde are employees of AstraZeneca. Dr Solomon has received research grants from Actelion, Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, Bristol Myers Squibb, Celladon, Cytokinetics, Eidos, Gilead, GlaxoSmithKline, Ionis, Lilly, Mesoblast, MyoKardia, National Institutes of Health/NHLBI, Neurotronik, Novartis, NovoNordisk, Respicardia, Sanofi Pasteur, Theracos; and consulted for Abbott, Action, Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boeringer-Ingelheim, Bristol Myers Squibb, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi-Sankyo, GlaxoSmithKline, Lilly, Merck, Myokardia, Novartis, Roche, Theracos, Quantum Genomics, Cardurion, Janssen, Cardiac Dimensions, Tenaya, Sanofi-Pasteur, Dinaqor, Tremeau, CellProThera, Moderna, American Regent and Sarepta. Dr McMurray’s employer, the University of Glasgow, has been remunerated by AstraZeneca for working on the DAPA-HF, DELIVER, and DETERMINE trials, Amgen, Boehringer Ingelheim, Cytokinetics, DalCor, GlaxoSmithKline, Pfizer, Theracos and Novartis; financial support from Bayer, Bristol Myers Squibb, Cardurion, KBP Biosciences, Ionis and Alnylam; and has received speaker’s fees from Abbott, Alkem Metabolics, Eris Lifesciences, Hikma, Lupin, Sun Pharmaceuticals, Medscape/Heart.Org, ProAdWise Communications, Radcliffe Cardiology, Servier and the Corpus; and is director of Global Clinical Trial Partners Ltd (GCTP).
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© 2022 The Authors
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