Abstract
Aims: In heart failure with reduced ejection fraction (HFrEF), there is an ‘obesity paradox’, where survival is better in patients with a higher body mass index (BMI) and weight loss is associated with worse outcomes. We examined the effect of a sodium–glucose co-transporter 2 inhibitor according to baseline BMI in the Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure trial (DAPA-HF). Methods and results: Body mass index was examined using standard categories, i.e. underweight (<18.5 kg/m2); normal weight (18.5–24.9 kg/m2); overweight (25.0–29.9 kg/m2); obesity class I (30.0–34.9 kg/m2); obesity class II (35.0–39.9 kg/m2); and obesity class III (≥40 kg/m2). The primary outcome in DAPA-HF was the composite of worsening heart failure or cardiovascular death. Overall, 1348 patients (28.4%) were under/normal-weight, 1722 (36.3%) overweight, 1013 (21.4%) obesity class I and 659 (13.9%) obesity class II/III. The unadjusted hazard ratio (95% confidence interval) for the primary outcome with obesity class 1, the lowest risk group, as reference was: under/normal-weight 1.41 (1.16–1.71), overweight 1.18 (0.97–1.42), obesity class II/III 1.37 (1.10–1.72). Patients with class I obesity were also at lowest risk of death. The effect of dapagliflozin on the primary outcome and other outcomes did not vary by baseline BMI, e.g. hazard ratio for primary outcome: under/normal-weight 0.74 (0.58–0.94), overweight 0.81 (0.65–1.02), obesity class I 0.68 (0.50–0.92), obesity class II/III 0.71 (0.51–1.00) (P-value for interaction = 0.79). The mean decrease in weight at 8 months with dapagliflozin was 0.9 (0.7–1.1) kg (P < 0.001). Conclusion: We confirmed an ‘obesity survival paradox’ in HFrEF. We showed that dapagliflozin was beneficial across the wide range of BMI studied. Clinical Trial Registration: ClinicalTrials.gov NCT03036124.
Originalsprog | Engelsk |
---|---|
Tidsskrift | European Journal of Heart Failure |
Vol/bind | 23 |
Udgave nummer | 10 |
Sider (fra-til) | 1662-1672 |
Antal sider | 11 |
ISSN | 1388-9842 |
DOI | |
Status | Udgivet - 2021 |
Bibliografisk note
Funding Information:P.S.J. reported his employer being paid by AstraZeneca for his time working on the study and receiving personal fees from and his employer being paid by Novartis; grants and personal fees from Boehringer Ingelheim; personal fees from Cytokinetics and Vifor Pharma outside the submitted work; and being the director of Global Clinical Trials Partners Ltd. K.F.D. reported his employer, the University of Glasgow, being paid by AstraZeneca (sponsor of DAPA‐HF) for his involvement in the DAPA‐HF trial and receiving personal fees from Eli Lilly outside the submitted work. J.B. reported receiving personal fees from AstraZeneca during the conduct of the study and grants from the Ministry of Health/Grant Agency for Health Research of the Czech Republic and personal fees from Novartis, Boehringer Ingelheim, Amgen, Medpace, and Pfizer outside the submitted work. C.E.C. reported receiving honorarium for lectures from AstraZeneca, Boehringer Ingelheim, Daiichi‐Sankyo, Merck Sharp & Dohme, Novartis, Pfizer, and Sanofi. M.D. reported receiving personal fees from AstraZeneca during the conduct of the study. J.H. reported receiving grants and personal fees from AstraZeneca Canada and Boerhinger Ingelheim/Eli Lilly during the conduct of the study and grants and personal fees from Servier Canada, Novartis, Pfizer, and Bayer; personal fees from Otsuka, Alnylam, and Akcea; grants from Medtronic; and serving on the medical advisory board for Caridiol outside the submitted work. C.E.A.L. reported receiving personal fees and financial reimbursement to the institution from AstraZeneca during the conduct of the study and personal fees from Novartis and Pfizer outside the submitted work. M.C.P. reported receiving lecture fees from AstraZeneca and Eli Lilly during the conduct of the study and personal fees from Novo Nordisk, AstraZeneca, NAPP Pharmaceuticals, Takeda Pharmaceutical, Alnylam, Bayer, Resverlogix, and Cardiorentis and grants and personal fees from Boehringer Ingelheim and Novartis outside the submitted work. M.S. reported receiving personal fees and nonfinancial support from AstraZeneca and personal fees from Novo Nordisk and Bohringer Ingelheim outside the submitted work. S.E.I. reported receiving personal fees from AstraZeneca during the conduct of the study and personal fees from AstraZeneca, Boehringer Ingelheim, Merck, VTV Therapeutics, Sanofi/Lexicon, and Novo Nordisk outside the submitted work. L.K. reported receiving grants from AstraZeneca to the institution for participation in Dapa‐HF steering committee during the conduct of the study and personal fees from speakers honorarium from AstraZeneca and Novartis outside the submitted work. M.N.K. reported receiving grants and personal fees from AstraZeneca and Boehringer Ingelheim and personal fees from Sanofi, Amgen, Novo Nordisk, Merck, Eisai, Janssen, Bayer, GlaxoSmithKline, Glytec, Intarcia, Novartis, Applied Therapeutics, Amarin, and Eli Lilly outside the submitted work. F.A.M. reported receiving personal fees from AstraZeneca during the conduct of the study. P.P. reported receiving personal fees and fees to his institution from participation as an investigator in clinical trials from AstraZeneca during the conduct of the study and from Boehringer Ingelheim, Servier, Novartis, Berlin‐Chemie, Bayer, Renal Guard Solutions, Pfizer, Respicardia, Cardiorentis, and Cibiem; grants, personal fees, and fees to his institution from Impulse Dynamics; and fees to his institution from Vifor, Corvia, and Revamp Medical outside the submitted work. M.S.S. reported receiving grants and personal fees from AstraZeneca during the conduct of the study; grants and personal fees from Amgen, Intarcia, Janssen Research and Development, Medicines Company, MedImmune, Merck, and Novartis; personal fees from Anthos Therapeutics, Bristol‐Myers Squibb, CVS Caremark, DalCor, Dyrnamix, Esperion, IFM Therapeutics, Ionis; and grants from Daiichi‐Sankyo, Bayer, Pfizer, Poxel, Eisai, GlaxoSmithKline, Quark Pharmaceuticals, and Takeda outside the submitted work; 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. S.D.S. reported receiving grants from AstraZeneca during the conduct of the study and grants from Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, Bristol‐Myers Squibb, Celladon, Cytokinetics, Eidos, Gilead, GlaxoSmithKline, Ionis, Lone Star Heart, Mesoblast, MyoKardia, National Institutes of Health/National Heart, Lung, and Blood Institute, Novartis, Sanofi Pasteur, and Theracos and personal fees from Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Bristol‐Myers Squibb, Cardior, Corvia, Cytokinetics, Daiichi‐Sankyo, Gilead, GlaxoSmithKline, Ironwood, Merck, Myokardia, Novartis, Roche, Takeda, Theracos, Quantum Genetics, Cardurion, AoBiome, Janssen, Cardiac Dimensions, and Tenaya outside the submitted work. O.B. reported receiving personal fees from AstraZeneca outside the submitted work. A.M.L. reported receiving being a full‐time employee of and shareholder in AstraZeneca during the conduct of the study. D.L. is an employee of AstraZeneca. M.S. reported receiving personal fees from and being a full‐time employee and shareholder of AstraZeneca outside the submitted work. J.J.V.M. reported receiving grants and his employer being paid by AstraZeneca, Theracos, and GlaxoSmithKline during the conduct of the study and grants and his employer being paid by Novartis, Amgen, Bristol‐Myers Squibb, Bayer, Abbvie, Dal‐Cor, Kidney Research UK, and Cardurion and grants from British Heart Foundation outside the submitted work. No other disclosures were reported. Conflict of interest:
Funding Information:
The DAPA‐HF trial was funded by AstraZeneca. C.A., M.C.P. and J.J.V.M. are supported by a British Heart Foundation Centre of Research Excellence Grant RE/18/6/34217.
Publisher Copyright:
© 2021 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.