With modern therapies for heart failure (HF) with reduced ejection fraction (HFrEF), some patients can improve their cardiac function during treatment. But despite this improvement in the ability of their hearts to pump, these patients with so called heart failure with improved ejection fraction (HFimpEF) remain at high risk for adverse outcomes. Unfortunately, they have been excluded from virtually all clinical trials in heart failure and there has been little evidence about how best to improve clinical management for this growing patient population. Researchers from Brigham and Women’s Hospital, a founding member of Mass General Brigham, and collaborators from the University of Minnesota and University of Glasgow have conducted an analysis that suggests that this patient population may further benefit from initiation of the SGLT2 inhibitor dapagliflozin, a heart failure medication that has received attention after presentations earlier this year on data from the randomized, controlled DELIVER clinical trial. In a prespecified analysis of data from the DELIVER trial, researchers looked at outcomes for 1,151 patients with HFimpEF and found that dapagliflozin reduced the primary composite outcome, first worsening heart failure events, cardiovascular death and total worsening heart failure events.
“These are essentially the first large-scale randomized outcomes data in patients with heart failure and improved ejection fraction,” said co-corresponding author Scott D. Solomon, MD, of the BWH Division of Cardiovascular Medicine. “As current therapy of heart failure with reduced ejection fraction gets better, and more and more patients show improvement, this group is becoming larger. These data suggest that addition of an SGLT2 inhibitor can benefit these patients and should inform treatment decision-making.”
Read more in Nature Medicine.
Paper cited: Vardeny O. “Dapagliflozin in heart failure with improved ejection fraction: a prespecified analysis of the DELIVER trial” Nature Medicine DOI: 10.1038/s41591-022-02102-9
Journal
Nature Medicine
DOI
10.1038/s41591-022-02102-9
COI Statement
O.V. has received institutional research support for DELIVER
from AstraZeneca and institutional research support from Bayer.
J.C.F. has received research grants from the National Institutes of
Health (NIH), has consulted with Novartis, Amgen, AstraZeneca,
Boehringer Ingelheim/Lilly, Abbott, Capricor, Windtree, LabCorp
and has provided support to AHA, NIH, HFSA and HRS. A.S.D. reports
institutional grant support from Abbott, Alnylam, AstraZeneca, Bayer,
Novartis and consulting fees from Abbott, Alnylam, AstraZeneca,
Avidity, Axon Therapeutics, Bayer, Biofourmis, Boston Scientific,
Cytokinetics, GSK, Merck, Novartis, Parxel, Regeneron, Roche and
Verily. P.S.J.’s employer has been remunerated for his work on the
DELIVER and DAPA-HF trials by AstraZeneca, reports consulting
and speakers fees for Novartis, AstraZeneca, Boheringer Ingelheim,
research funding from Boehringer Ingelheim and remuneration for
clinical trial work from Novo Nordisk and Bayer. B.C. has received
consulting fees from Amgen, Cardurion, Corvia and Novartis. M.V.
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, speaker engagements with Novartis and Roche
Diagnostics and participates on clinical trial committees for
studies sponsored by Galmed, Novartis, Bayer AG, Occlutech and
Impulse Dynamics. R.A.D.B. has received research grants and/
or fees from AstraZeneca, Abbott, Boehringer Ingelheim, Cardior
Pharmaceuticals, Ionis Pharmaceuticals, Novo Nordisk and Roche,
and has had speaker engagements with Abbott, AstraZeneca, Bayer,
Bristol Myers Squibb, Novartis, and Roche. A.F.H. has received
research grants from American Regent, Amgen, AstraZeneca,
Bayer, Boehringer Ingelheim, Merck, Novartis, Somologic and Verily,
and has served as a consultant on the advisory boards for Amgen,
AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific,
Bristol Myers Squibb, Cytokinetics, Eidos, Intercept, Merck and
Novartis. C.S.P.L. 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
consultant on the advisory board/steering committee/executive
committee for Actelion, Alleviant Medical, Allysta Pharma, Amgen,
AnaCardio AB, Applied Therapeutics, AstraZeneca, Bayer, Boehringer
Ingelheim, Boston Scientific, Cytokinetics, Darma, EchoNous, Eli
Lilly, Impulse Dynamics, Ionis Pharmaceutical, Janssen Research &
Development LLC, Medscape/WebMD Global LLC, Merck, Novartis,
Novo Nordisk, Prosciento, Radcliffe Group Ltd., Roche Diagnostics,
Sanofi, Siemens Healthcare Diagnostics and Us2.ai and serves as
cofounder and nonexecutive director of Us2.ai. S.E.I. has served
on clinical trial committees or as a consultant to AstraZeneca,
Boehringer Ingelheim, Novo Nordisk, Lexicon, Merck, Pfizer, vTv
Therapeutics, Abbott and Esperion, and has given lectures sponsored
by AstraZeneca and Boehringer Ingelheim. F.A.M. has received
consultation fees and research grants from AstraZeneca, Baliarda,
Bayer, Boheringer Ingelheim, Bristol Myers Squibb, Gador, Milestone,
Novartis, Pfizer and St. Lukes University. M.N.K. has received research
grant support from AstraZeneca and Boehringer Ingelheim, has
served as a consultant on the advisory board for Alnylam, Amgen,
Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim,
Eli Lilly, Esperion Therapeutics, Janssen, Lexicon, Merck (Diabetes
and Cardiovascular), Novo Nordisk, Sanofi, Pharmacosmos and Vifor
Pharma, has received other research support from AstraZeneca and
has received honoraria from AstraZeneca, Boehringer Ingelheim
and Novo Nordisk. D.D. has received consulting fees from Frontier
Science, Actelion, Bristol Myers Squibb, Medtronic, Boston Scientific,
GSK and Merck and has received consulting fees and is the owner
of DL DeMets Consulting. E.O. has received research funds (paid
to her institution) for clinical trials from American Regent, Amgen,
AstraZeneca, Bayer, Cardurion, Cytokinetics, Novartis and Pfizer, and
has received consulting fees from AstraZeneca, Bayer, Boehringer
Ingelheim, Cytokinetics, Eli Lilly and Janssen, as well as speaker
fees from AstraZeneca, Bayer and Boehringer Ingelheim. J.C.C. has
received research grants from Novartis, Orion Pharma, AstraZeneca,
Vifor Pharma, Bristol Myers Squibb, and has consulted for Novartis,
Orion Pharma, AstraZeneca, Vifor Pharma, Bayer, Boehringer
Ingelheim, Gilead, Menarini and Pfizer. J.D. also received research
grants from AstraZeneca, Servier Poland and lecture fees from
Bayer Healthcare, Boehringer Ingelheim and Novartis. C.C. has
received honoraria from AstraZeneca, Bayer, Boehringer Ingelheim,
Daiichi-Sankyo, Eli Lilly, Menarini, MSD, Novartis, Pfizer and Sanofi.
M.K. reports personal fees from Daiichi-Sankyo, personal fees from
Viatris, personal fees from Ono, grants from Novartis, grants and
personal fees from Tanabe-Mitubishi, grants from Takeda, grants
and personal fees from AstraZeneca, grants and personal fees from
Boehringer Ingelheim, grants from Kowa, personal fees from Otsuka
and personal fees from Eli Lilly, outside the submitted work. M.P. and
A.M.L. are employees and shareholders of AstraZeneca. D.L. was an
AstraZeneca employee when the DELIVER trial was conducted. D.L.
is now affiliated with Department of Medicine, Norrtälje Hospital,
Norrtälje, Sweden. J.J.V.M. has received payments through Glasgow
University for work on clinical trials, consulting and other activities
from Alnylam, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim,
Bristol Myers Squibb, Cardurion, Cytokinetics, Dal-Cor, GSK, Ionis,
KBP Biosciences, Novartis, Pfizer and Theracos, personal lecture
fees from the Corpus, Abbott, Hikma, Sun Pharmaceuticals,
Medscape/Heart.Org, Radcliffe Cardiology, Servier Director and
Global Clinical Trial Partners. S.D.S. has received research grants
from Actelion, Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer,
Bristol Myers Squibb, Celladon, Cytokinetics, Eidos, Gilead, GSK,
Ionis, Lilly, Mesoblast, MyoKardia, NIH/National Heart, Lung, and
Blood Institute, Neurotronik, Novartis, Novo Nordisk, 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, GSK, 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. S.Z. received research grant support, served on
advisory boards for or had speaker engagements with Abbott, Akcea
Therapeutics, AstraZeneca, Amgen, Alnylam, Bayer, Bristol Myers
Squibb, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, Novartis,
Novo Nordisk, Otsuka, Pfizer, Servier and Vifor Pharma and serves
on a clinical trial steering committee as a national lead for studies
sponsored by AstraZeneca, Bayer, Boehringer Ingelheim, Merck and
Novartis.
