Dapagliflozin in Patients Recently Hospitalized With Heart Failure and Mildly Reduced or Preserved Ejection Fraction

Jonathan W. Cunningham, Muthiah Vaduganathan, Brian L. Claggett, Ian J. Kulac, Akshay S. Desai, Pardeep S. Jhund, Rudolf A. de Boer, David DeMets, Adrian F. Hernandez, Silvio E. Inzucchi, Mikhail N. Kosiborod, Carolyn S.P. Lam, Felipe Martinez, Sanjiv J. Shah, Martina M. McGrath, Eileen O'Meara, Ulrica Wilderäng, Daniel Lindholm, Magnus Petersson, Anna Maria LangkildeJohn J.V. McMurray, Scott D. Solomon*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

57 Citations (Scopus)

Abstract

Background: Patients recently hospitalized for heart failure (HF) are at high risk for rehospitalization and death. Objectives: The purpose of this study was to investigate clinical outcomes and response to dapagliflozin in patients with HF with mildly reduced or preserved left ventricular ejection fraction (LVEF) who were enrolled during or following hospitalization. Methods: The DELIVER (Dapagliflozin Evaluation to Improve the LIVES of Patients With PReserved Ejection Fraction Heart Failure) trial randomized patients with HF and LVEF >40% to dapagliflozin or placebo. DELIVER permitted randomization during or shortly after hospitalization for HF in clinically stable patients off intravenous HF therapies. This prespecified analysis investigated whether recent HF hospitalization modified risk of clinical events or response to dapagliflozin. The primary outcome was worsening HF event or cardiovascular death. Results: Of 6,263 patients in DELIVER, 654 (10.4%) were randomized during HF hospitalization or within 30 days of discharge. Recent HF hospitalization was associated with greater risk of the primary outcome after multivariable adjustment (HR: 1.88; 95% CI: 1.60-2.21; P < 0.001). Dapagliflozin reduced the primary outcome by 22% in recently hospitalized patients (HR: 0.78; 95% CI: 0.60-1.03) and 18% in patients without recent hospitalization (HR: 0.82; 95% CI: 0.72-0.94; Pinteraction = 0.71). Rates of adverse events, including volume depletion, diabetic ketoacidosis, or renal events, were similar with dapagliflozin and placebo in recently hospitalized patients. Conclusions: Dapagliflozin safely reduced risk of worsening HF or cardiovascular death similarly in patients with and without history of recent HF hospitalization. Starting dapagliflozin during or shortly after HF hospitalization in patients with mildly reduced or preserved LVEF appears safe and effective.

Original languageEnglish
Pages (from-to)1302-1310
Number of pages9
JournalJournal of the American College of Cardiology
Volume80
Issue number14
DOIs
Publication statusPublished - 4 Oct 2022
Externally publishedYes

Bibliographical note

Funding Information:
DELIVER was sponsored by AstraZeneca. Dr Cunningham has received grant support from the American College of Cardiology/Association of Black Cardiologists Bristol Myers Squibb Research Award. Dr Claggett has received consulting fees from Amgen, Cardurion, Corvia, and Novartis. Dr Vaduganathan has received research grant support or served on advisory boards for American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, Boehringer Ingelheim, Cytokinetics, Lexicon Pharmaceuticals, Novartis, Pharmacosmos, Relypsa, Roche Diagnostics, Sanofi, and Tricog Health; has speaker engagements with AstraZeneca, Novartis, and Roche Diagnostics; and participates on clinical trial committees for studies sponsored by Galmed, Novartis, Bayer AG, Occlutech, and Impulse Dynamics. Dr Desai has received grant support from Abbott, Alnylam, AstraZeneca, Bayer, and Novartis; and has received consulting fees from Abbott, Alnylam, AstraZeneca, Avidity, Axon Therapeutics, Bayer, Biofourmis, Boston Scientific, Cytokinetics, GlaxoSmithKline, Merck, Novartis, Parxel, Regeneron, Roche, and Verily. Dr Jhund's employer has been remunerated for his work on the DELIVER and DAPA-HF trials by AstraZeneca; has received consulting and speaker fees from Novartis, AstraZeneca, and Boehringer Ingelheim; has received research funding from Boehringer Ingelheim; and has received remuneration for clinical trial work from Novo Nordisk and Bayer. Dr de Boer has received research grants and/or fees from AstraZeneca, Abbott, Boehringer Ingelheim, Cardior Pharmaceuticals GmbH, Ionis Pharmaceuticals, Novo Nordisk, and Roche; and has had speaker engagements with Abbott, AstraZeneca, Bayer, Bristol Myers Squibb, Novartis, and Roche. Dr DeMets has received consulting fees from Frontier Science, Actelion, Bristol Myers Squibb, Medtronic, Boston Scientific, GlaxoSmithKline, and Merck; and has received consulting fees and is the owner of DL DeMets Consulting. Dr Hernandez has received research grant support from American Regent, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Merck, Novartis, Somologic, and Verily; and has served as a consultant or on the Advisory Board for Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cytokinetics, Eidos, Intercept, Merck, and Novartis. Dr Inzucchi has served on clinical trial committees and/or as a consultant to AstraZeneca, Boehringer Ingelheim, Novo Nordisk, Lexicon, Merck, Pfizer, vTv Therapeutics, Abbott, and Esperion; and has delivered lectures sponsored by AstraZeneca and Boehringer Ingelheim. Dr Kosiborod has received research grant support from AstraZeneca and Boehringer Ingelheim; has served as a consultant or on an advisory board for Alnylam, Amgen, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Esperion Therapeutics, Eli Lilly, Janssen, Lexicon, Merck (Diabetes and Cardiovascular), Pharmacosmos, Novo Nordisk, Sanofi, and Vifor; has received other research support from AstraZeneca; and has received honoraria from AstraZeneca, Boehringer Ingelheim, and Novo Nordisk. Dr Lam is supported by a Clinician Scientist Award from the National Medical Research Council of Singapore; has received research support from Bayer and Roche Diagnostics; has served as a consultant or has been on the Advisory Board/Steering Committee/Executive Committee for AstraZeneca, Abbott, Actelion, Alleviant Medical, Allysta Pharma, Amgen, AnaCardio AB, Applied Therapeutics, Bayer, Boehringer Ingelheim, Boston Scientific, Cytokinetics, Darma Inc, EchoNous Inc, Eli Lilly, Impulse Dynamics, Ionis Pharmaceutical, Janssen Research & Development LLC, Medscape/WebMD Global LLC, Merck, Novartis, Novo Nordisk, Prosciento Inc, Radcliffe Group Ltd, Roche Diagnostics, Sanofi, Siemens Healthcare Diagnostics, and Us2.ai; and serves as cofounder and nonexecutive director of Us2.ai. Dr Martinez has received personal fees from AstraZeneca. Dr Shah has received research grants from the National Institutes of Health (U54 HL160273, R01 HL107577, R01 HL127028, R01 HL140731, R01 HL149423), Actelion, AstraZeneca, Corvia, Novartis, and Pfizer; and has received consulting fees from Abbott, Actelion, AstraZeneca, Amgen, Aria CV, Axon Therapies, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardiora, Coridea, CVRx, Cyclerion, Cytokinetics, Edwards Lifesciences, Eidos, Eisai, Imara, Impulse Dynamics, GSK, Intellia, Ionis, Ironwood, Lilly, Merck, MyoKardia, Novartis, Novo Nordisk, Pfizer, Prothena, Regeneron, Rivus, Sanofi, Sardocor, Shifamed, Tenax, Tenaya, and United Therapeutics. Dr O’Meara has received research funds (paid to her institution) for clinical trials from American Regent, Amgen, AstraZeneca, Bayer, Cardurion, Cytokinetics, Novartis, and Pfizer; has received consulting fees paid to her or her institutions from AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Eli Lilly, and Janssen; and has received speaker fees from AstraZeneca, Bayer, and Boehringer Ingelheim. Drs Wilderäng, Lindholm, Petersson, and Langkilde are employees and shareholders of AstraZeneca. Dr McMurray has received funding to his institution, Glasgow University, for his work on clinical trials, consulting, and other research activities from Alnylam, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardurion, Cytokinetics, Dal-Cor, GlaxoSmithKline, Ionis, KBP Biosciences, Novartis, Pfizer, and Theracos; and has received personal lecture fees from the Corpus, Abbott, Hickma, Sun Pharmaceuticals, Medscape/Heart.Org, Radcliffe Cardiology, Servier Director, and Global Clinical Trial Partners (GCTP). 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, NovoNordisk, Respicardia, Sanofi Pasteur, Theracos, and US2.AI; 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, Sarepta, Lexicon, Anacardio, and Akros. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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