Effects of Dapagliflozin in Asian Patients With Heart Failure and Reduced Ejection Fraction in DAPA-HF.

Background: Patients with heart failure with reduced ejection fraction (HFrEF) in Asia exhibit many differences from those in other parts of the world.
Objectives: This study sought to investigate the efficacy and safety of dapagliflozin, compared with placebo, in HFrEF patients in Asia, compared with those elsewhere, enrolled in the DAPA-HF (Dapagliflozin and Prevention of Adverse-outcomes in Heart Failure) trial.
Methods: Patients in New York Heart Association functional class II to IV with a left ventricular ejection fraction ≤40% and elevated N-terminal pro-B-type natriuretic peptide were eligible for the DAPA-HF trial. The primary outcome in the DAPA-HF trial was the composite of an episode of worsening HF (HF hospitalization or urgent HF visit requiring intravenous therapy) or cardiovascular death.
Results: Of the 4,744 patients in the DAPA-HF trial, 1,096 (23.1%) were enrolled in Asia; 721 (15.2% overall, 65.8% of patients in Asia) were enrolled in East Asia (237 in China, 343 in Japan, and 141 in Taiwan), 138 (2.9% overall, 12.6% in Asia) in South-East Asia (Vietnam), and 237 (5.0% overall, 21.6% in Asia) in South Asia (India). Patients from Asia had similar rates of worsening HF events and mortality compared with patients elsewhere. Compared with placebo, dapagliflozin reduced the risk of the primary endpoint to the same extent in patients from Asia (HR: 0.65; 95% CI: 0.49 to 0.87) as elsewhere (HR: 0.77; 95% CI: 0.66 to 0.89) ( P for interaction = 0.32). Consistent benefits were observed for the other prespecified outcomes and among the regions of Asia. Study drug discontinuation and prespecified adverse events did not differ between regions.
Conclusions: Dapagliflozin, compared with placebo, reduced the risk of worsening HF events and cardiovascular death to the same extent in Asian patients as elsewhere. (Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure [DAPA-HF]; NCT03036124).
Competing Interests: This study was funded by AstraZeneca. Dr McMurray was supported by a British Heart Foundation Centre of Research Excellence Grant RE/18/6/34217. Dr Docherty has received grant support from Novartis and speaker fees from AstraZeneca; and his employer, the University of Glasgow, has been remunerated for his time spent working on the DAPA-HF trial. Dr Anand has received fees for serving on a steering committee from AstraZeneca, ARCA biopharma, Amgen, and LivaNova; for serving as chair of a data and safety monitoring board from Boston Scientific; for serving on an endpoint committee from Boehringer Ingelheim; and for serving on an advisory board from Zensun. Dr Chiang has received honorarium for lectures from AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Merck Sharp & Dohme, Novartis, Pfizer, and Sanofi. Dr Chopra has received consulting fees from Novartis. Dr Desai has received consulting fees from Abbott, Biofourmis, Boston Scientific, Boehringer Ingelheim, DalCor Pharmaceuticals, and Regeneron; grant support (paid to Brigham and Women’s Hospital) and consulting fees from Alnylam Pharmaceuticals and Novartis; and advisory board fees from Corvidia and Relypsa. Dr Kitakaze has received grant support and lecture fees from Astellas Pharma, Sanofi, Pfizer, Ono Pharmaceutical, Novartis, and Mitsubishi Tanabe Pharma; lecture fees from Daiichi Sankyo, Bayer, Boehringer Ingelheim, Kowa Pharmaceutical, Sawai Pharmaceutical, MSD, Shionogi, Kureha, Taisho Toyama Pharmaceutical, Takeda Pharmaceutical, and Toa Eiyo; and manuscript fees from Japan Medical Data Center. Dr Verma has 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 Vinh has reported that he has no relationships relevant to the contents of this paper to disclose. 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 other support from AstraZeneca and personal fees from Novartis and Bristol Myers Squibb as a speaker. Dr Kosiborod has received personal fees from AstraZeneca; received grants, personal fees, and other from AstraZeneca; received grants and personal fees from Boehringer Ingelheim; and served as consultant for Vifor Pharma and personal fees from Sanofi, Amgen, Novo Nordisk, Merck (Diabetes), Janssen, Bayer, GlaxoSmithKline, Glytec, Novartis, Applied Therapeutics, Amarin, and Eli Lilly. Dr Martinez has received personal fees from AstraZeneca. Drs Bengtsson, Langkilde, and Sjostrand are full-time employees of AstraZeneca. Dr Ponikowski has received personal fees and other from AstraZeneca, Boehringer Ingelheim, Bayer, BMS, Cibiem, Novartis, and RenalGuard; personal fees from Pfizer, Servier, Respicardia, and Berlin-Chemie; other from 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, DalCor, Dyrnamix, Esperion, IFM Therapeutics, and Ionis. Dr Sabatine has served as 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. Dr Solomon has received grants from AstraZeneca, Bellerophon, Celladon, Ionis, Lone Star Heart, Mesoblast, National Institutes of Health/National Heart, Lung, and Blood Institute, Sanofi Pasteur, and Eidos; grants and personal fees from Alnylam, Amgen, AstraZeneca, BMS, Gilead, GSK, MyoKardia, Novartis, Theracos, Bayer, and Cytokinetics; and personal fees from Akros, Corvia, Ironwood, Merck, Roche, Takeda, Quantum Genomics, AoBiome, Janssen, Cardiac Dimensions, Tenaya, and Daiichi Sankyo. Dr Jhund has received other from AstraZeneca; personal fees from Novartis and Cytokinetics; and grants from Boehringer Ingelheim. Dr McMurray has received nonfinancial support and other from AstraZeneca, Cardiorentis, Amgen, Oxford University/Bayer, Theracos, Abbvie, Novartis, GlaxoSmithKline, Vifor-Fresenius, Kidney Research UK, and Novartis; and other support from Bayer, DalCor, Pfizer, Merck, and Bristol Myers Squibb.
(© 2022 The Authors.)