Effect of Dapagliflozin on 6-Minute Walk Distance in Heart Failure With Preserved Ejection Fraction: PRESERVED-HF.

Autor:	Lewis GD; Cardiology Division, Massachusetts General Hospital, Boston (G.D.L., L.P.C.)., Gosch K; Saint Luke's Mid America Heart Institute, Kansas City, MO (K.G., M.E.N., S.L.W., T.K., M.N.K., A.J.S.).; University of Missouri-Kansas City School of Medicine (K.G., M.E.N., T.K., M.N.K., A.J.S.)., Cohen LP; Cardiology Division, Massachusetts General Hospital, Boston (G.D.L., L.P.C.)., Nassif ME; Saint Luke's Mid America Heart Institute, Kansas City, MO (K.G., M.E.N., S.L.W., T.K., M.N.K., A.J.S.).; University of Missouri-Kansas City School of Medicine (K.G., M.E.N., T.K., M.N.K., A.J.S.)., Windsor SL; Saint Luke's Mid America Heart Institute, Kansas City, MO (K.G., M.E.N., S.L.W., T.K., M.N.K., A.J.S.)., Borlaug BA; Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (B.A.B.)., Kitzman DW; Department of Internal Medicine, Sections on Cardiovascular Medicine and Geriatrics, Wake Forest University School of Medicine, Winston-Salem, NC (D.W.K.)., Shah SJ; Department of Medicine and Bluhm Cardiovascular Institute, Division of Cardiology, Northwestern University Feinberg School of Medicine, Chicago, IL (S.J.S., S.S.K.)., Khumri T; Saint Luke's Mid America Heart Institute, Kansas City, MO (K.G., M.E.N., S.L.W., T.K., M.N.K., A.J.S.).; University of Missouri-Kansas City School of Medicine (K.G., M.E.N., T.K., M.N.K., A.J.S.)., Umpierrez G; Emory University, Atlanta, GA (G.U.)., Lamba S; First Coast Cardiovascular Institute, Jacksonville, FL (S.L.)., Sharma K; Johns Hopkins University School of Medicine, Baltimore, MD (K.S.)., Khan SS; Department of Medicine and Bluhm Cardiovascular Institute, Division of Cardiology, Northwestern University Feinberg School of Medicine, Chicago, IL (S.J.S., S.S.K.)., Kosiborod MN; Cardiology Division, Massachusetts General Hospital, Boston (G.D.L., L.P.C.).; University of Missouri-Kansas City School of Medicine (K.G., M.E.N., T.K., M.N.K., A.J.S.)., Sauer AJ; Saint Luke's Mid America Heart Institute, Kansas City, MO (K.G., M.E.N., S.L.W., T.K., M.N.K., A.J.S.).; University of Missouri-Kansas City School of Medicine (K.G., M.E.N., T.K., M.N.K., A.J.S.).
Jazyk:	angličtina
Zdroj:	Circulation. Heart failure [Circ Heart Fail] 2023 Nov; Vol. 16 (11), pp. e010633. Date of Electronic Publication: 2023 Oct 23.
DOI:	10.1161/CIRCHEARTFAILURE.123.010633
Abstrakt:	Background: Heart failure with preserved ejection fraction is associated with significant functional limitations, yet treatments for improving exercise performance have been elusive. We sought to explore the association between prespecified patient characteristics and changes in 6-minute walk distance that constitute a clinically significant response to dapagliflozin. Methods: We performed a responder analysis to understand patient characteristics associated with clinically meaningful improvement in 6-minute walk test (6MWT) distance ≥15 m among patients randomized to 12 weeks of dapagliflozin versus placebo in the double-blind PRESERVED-HF trial (Effects of Dapagliflozin on Biomarkers, Symptoms and Functional Status in Patients With Preserved Ejection Fraction Heart Failure). Results: A total of 289 randomized patients had 6MWT distance completed at baseline and 12 weeks. Patients randomized to dapagliflozin improved walking distance by ≥15 m more frequently than those on placebo (n=64, 44% versus n=48, 34%). After adjusting for baseline covariates, patients randomized to dapagliflozin were more likely to experience a clinically meaningful improvement in 6MWT distance compared with those that received placebo (adjusted odds ratio, 1.66 [95% CI, 1.00-2.75]; P =0.05). Dapagliflozin-treated patients were also less likely to have a ≥15 m reduction in 6MWT distance compared with placebo-treated patients (adjusted odds ratio, 0.56 [95% CI, 0.33-0.94]; P =0.03). These results were consistent across all prespecified subgroups (all P values for interaction were not significant). Conclusions: Compared with those on placebo, patients with heart failure with preserved ejection fraction randomized to dapagliflozin were more likely to experience a clinically meaningful improvement and less likely to experience a deterioration in physical function over 12 weeks as measured by 6MWT distance. Beneficial response to dapagliflozin was consistent across prespecified subgroups. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03030235. Competing Interests: Disclosures Dr Lewis reports research funding from the National Institutes of Health (NIH) R01-HL 151841, R01-HL131029, R01-HL159514, U01-HL160278, Amgen, Cytokinetics, Applied Therapeutics, AstraZeneca, SoniVie, NXT, and Rivus. He has received honoraria for advisory boards outside of the current study from Pfizer, Merck, Boehringer-Ingelheim, NXT, American Regent, Cyclerion, Cytokinetics, Amgen, RIVUS, and NXT and receives royalties from UpToDate for scientific content authorship related to exercise physiology. Dr Nassif is a consultant to Vifor and has received research support from Cytokinetics. Dr Borlaug receives research support from the NIH (R01 HL128526, R01 HL162828, and U01 HL160226) and the US Department of Defense (W81XWH2210245), and research grant funding from AstraZeneca, Axon, GlaxoSmithKline, Medtronic, Mesoblast, Novo Nordisk, and Tenax Therapeutics. Dr Borlaug has served as a consultant for Actelion, Amgen, Aria, Axon Therapies, BD, Boehringer-Ingelheim, Cytokinetics, Edwards Lifesciences, Eli Lilly, Imbria, Janssen, Merck, Novo Nordisk, NGM, NXT, and VADovations and is named inventor (US Patent no. 10,307,179) for the tools and approach for a minimally invasive pericardial modification procedure to treat heart failure. Dr Kitzman has received honoraria as a consultant for Boehringer-Ingelheim, Novo Nordisk, AstraZeneca, Corvia, Rivus, Keyto, Saint Luke’s Medical Center, and Novartis and grant funding from Novartis, Bayer, Novo Nordisk, Rivus, Saint Luke’s Medical Center, and AstraZeneca and stock ownership in Gilead Sciences. Dr Shah is supported by research grants from the NIH (U54 HL160273, R01 HL140731, and 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 Umpierrez is partly supported by research grants from the NIH/National Center for Advancing Translational Sciences (UL 3UL1TR002378-05S2) from the Clinical and Translational Science Award program, and from the NIH and National Center for Research Resources (NIH/National Institute of Diabetes and Digestive and Kidney Diseases 2P30DK111024-06). He has also received research support (to Emory University) from Dexcom, Bayer, Abbott, and AstraZeneca. Dr Sharma is an advisory board member and consultant for Alleviant, AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol Myers Squibb, Cytokinetics, Janssen, Novartis, Novo Nordisk, and RIVUS and receives honoraria. Dr Khan receives funding from the American Heart Association (19TPA34890060) and NIH (1R01HL159250). Dr Kosiborod receives grant/research support from AstraZeneca, Boehringer-Ingelheim, and Pfizer; honoraria from AstraZeneca, Boehringer-Ingelheim, and Novo Nordisk; is a consultant for 35Pharma, Alnylam, Amgen, Applied Therapeutics, AstraZeneca, Bayer, Boehringer-Ingelheim, Cytokinetics, Dexcom, Eli Lilly, Esperion Therapeutics, Imbria Pharmaceuticals, Janssen, Lexicon, Merck (Diabetes and Cardiovascular), Novo Nordisk, Pharmacosmos, Pfizer, Sanofi, scPharmaceuticals, Structure Therapeutics, Vifor Pharma, and Youngene Therapeutics; and has stock options from Artera Health and Saghmos Therapeutics. Dr Sauer is a consultant for Bayer, Abbott, Acorai, Biotronik, Boston Scientific, Edwards Life Sciences, Impulse Dynamics, Medtronics, Story Health, and Vifor Pharma and owns stock in ISHI. The other authors report no disclosures.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu