Efficacy of Dapagliflozin in Black Versus White Patients With Heart Failure and Reduced Ejection Fraction.

OBJECTIVES

This study sought to investigate the efficacy and safety of dapagliflozin in Black and White patients with heart failure (HF) with reduced ejection fraction (HFrEF) enrolled in DAPA-HF (Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure).

BACKGROUND

Black patients may respond differently to certain treatments for HFrEF than White patients.

METHODS

Patients with New York Heart Association functional class II to IV with an ejection fraction of ≤40% and elevated N-terminal pro-B-type natriuretic peptide were eligible for DAPA-HF. Because >99% of Black patients were randomized in the Americas, this post hoc analysis considered Black and White patients enrolled only in North and South America. The primary outcome was the composite of a worsening HF event (HF hospitalization or urgent HF visit requiring intravenous therapy) or cardiovascular death.

RESULTS

Of the 4,744 patients randomized in DAPA-HF, 1,494 (31.5%) were enrolled in the Americas. Of these, 1,181 (79.0%) were White, and 225 (15.1%) were Black. Black patients had a higher rate of worsening HF events, but not mortality, compared with White patients. Compared with placebo, dapagliflozin reduced the risk of the primary endpoint similarly in Black patients (HR: 0.62; 95% CI: 0.37-1.03) and White patients (HR: 0.68; 95% CI: 0.52-0.90; P-interaction = 0.70). Consistent benefits were observed for other prespecified outcomes, including the composite of total (first and repeat) HF hospitalizations and cardiovascular death (P-interaction = 0.43) and Kansas City Cardiomyopathy Questionnaire total symptom score. Study drug discontinuation and serious adverse events were not more frequent in the dapagliflozin group than in the placebo group in either Black or White patients.

CONCLUSIONS

Dapagliflozin reduced the risk of worsening HF and cardiovascular death, and it improved symptoms, similarly in Black and White patients without an increase in adverse events. (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).

Informations de copyright

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Funding Support and Author Disclosures DAPA-HF was funded by AstraZeneca. Dr McMurray 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 he has also received speaker fees from AstraZeneca and Eli Lilly. Dr Ogunniyi has received research grants from AstraZeneca, Boehringer Ingelheim, and Zoll and Advisory Board fees from Pfizer. Dr Desai has received grants and personal fees from AstraZeneca during the conduct of the study; personal fees from Abbott, Biofourmis, Boston Scientific, Boehringer Ingelheim, Corvidia, DalCor Pharma, Relypsa, Regeneron, and Merck; grants and personal fees from Alnylam and Novartis; and personal fees from Amgen, outside the submitted work. Dr Diez has received personal fees from AstraZeneca. Dr Howlett has received research grants from University Hospital Foundation, Pfizer, and Novartis; consulting fees from AstraZeneca, Bayer, Novartis, Merck, Janssen, Otsuka, Servier, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Akcea, Alnylam, and Pfizer; speaker fees from AstraZeneca, Bayer, Novartis, Merck, Janssen, Servier, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, and Pfizer; and has participated on a Data Safety Monitoring Board or Advisory Board for Novartis, AstraZeneca, and Medtronic. Dr Nicolau has received research grants and personal fees from Vifor Pharma (National Lead Investigator [NLI]/Steering Committee [SC] member for AFFIRM); research grants from AstraZeneca (NLI), Bayer (Principal Investigator [PI] Compass), Esperion and CLS Behring (NLI/SC member), DalCor (NLI), Janssen (NLI/SC member), Novartis (PI, consultant), Novo Nordisk (PI), and Sanofi (NLI, PI, Advisory Board); and personal fees from Amgen (consultant), Bayer, Daiichi-Sankyo (speaker), Novartis, Sanofi, and Servier (speaker, Advisory Board). Dr O’Meara or her institution has received financial support for clinical trials from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Merck, and Novartis; has served as a consultant or speaker for Amgen, Boehringer Ingelheim, Novartis, and AstraZeneca. Dr Verma has received personal fees from AstraZeneca, Sun Pharmaceuticals, and Toronto Knowledge Translation Working Group during the conduct of the study; grants and personal fees from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, and Merck; grants from Bristol Myers Squibb; and personal fees from Eli Lilly, Janssen, Novartis, Novo Nordisk, and Sanofi. 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 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, Novo Nordisk, Merck (Diabetes), Janssen, Bayer, Applied Therapeutics, and Eli Lilly. Dr Lindholm is an employee of AstraZeneca. Dr Martinez has received personal fees from AstraZeneca. Dr Bengtsson is an employee of 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, and Berlin-Chemie; financial support 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, Dal-Cor, Dyrnamix, Esperion, IFM Therapeutics, and Ionis; and 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. Dr Sjöstrand is an employee 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/National Heart, Lung, and Blood Institute, Neurotronik, Novartis, Novo Nordisk, Respicardia, Sanofi Pasteur, and Theracos and has consulted for Abbott, Action, Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boehringer 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 Langkilde is an employee of AstraZeneca. Dr Jhund’s employer (University of Glasgow) has been remunerated by AstraZeneca for involvement in the DAPA-HF and DELIVER trials; has received speaker and Advisory Board fees from Novartis; and Advisory Board fees and grants from Boehringer Ingelheim. Dr McMurray’s employer, the University of Glasgow, has been remunerated by AstraZeneca for working on the DAPA-HF, DELIVER, and DETERMINE trials as well as Amgen, Boehringer Ingelheim, Cytokinetics, DalCor, GlaxoSmithKline, Pfizer, Theracos, and Novartis; has received other support from Bayer, Bristol Myers Squibb, Cardurion, KBP Biosciences, Ionis, and Alnylam; has received speaker 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.