TY - JOUR

T1 - Dapagliflozin in HFrEF Patients Treated With Mineralocorticoid Receptor Antagonists

T2 - An Analysis of DAPA-HF

AU - Shen, Li

AU - Kristensen, Søren Lund

AU - Bengtsson, Olof

AU - Böhm, Michael

AU - de Boer, Rudolf A.

AU - Docherty, Kieran F.

AU - Inzucchi, Silvio E.

AU - Katova, Tzvetana

AU - Køber, Lars

AU - Kosiborod, Mikhail N.

AU - Langkilde, Anna Maria

AU - Lindholm, Daniel

AU - Martinez, M. Felipe A.

AU - O'Meara, Eileen

AU - Nicolau, Jose C.

AU - Petrie, Mark C.

AU - Ponikowski, Piotr

AU - Sabatine, Marc S.

AU - Schou, Morten

AU - Sjöstrand, Mikaela

AU - Solomon, Scott D.

AU - Jhund, Pardeep S.

AU - McMurray, John J.V.

N1 - Funding Information: DAPA-HF was funded by AstraZeneca. Drs. Bengtsson, Sjöstrand, Langkilde and Lindholm are employed by AstraZeneca. Dr. Böhm has been supported by the Deutsche Forschungsgemeinschaft (SFB TTR 219, S-01); and has received consultant and speaking honoraria from Abbott, AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol Myers Squibb, Medtronic, Novartis, ReCor, Servier, and Vifor. Dr. de Boer has received grants to his institution from AstraZeneca, Abbott, Bristol Myers Squibb, Novo Nordisk, and Roche and personal fees AstraZeneca, Abbott, Novartis, and Roche. Dr. Docherty has received payments to his institution from AstraZeneca during the conduct and analysis of the trial, grants from Novartis, and personal fees from Eli Lilly. Dr. Inzucchi received advisory fees from AstraZeneca and Zafgen, lecture fees and consulting fees for serving as a clinical-trial publications committee member, reimbursement for medical writing, travel support from Boehringer Ingelheim, fees for serving on a steering committee, travel support from Sanofi–Lexicon, lecture fees, consulting fees, and travel support from Merck, and advisory fees and travel support from vTv Therapeutics and Abbott–Alere. Dr. Katova is receiving fees for serving as national coordinator of a trial from Novartis and AstraZeneca. Dr. Køber has received payments to his institution from AstraZeneca during the conduct of the trial and lecture fees from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb and Novartis. Dr. Kosiboro received grant support, honoraria, and research support from AstraZeneca, grant support and honoraria from Boehringer Ingelheim, and honoraria from Sanofi, Amgen, Novo Nordisk, Merck (Diabetes), Eisai, Janssen, Bayer, GlaxoSmithKline, Glytec, Intarcia Therapeutics, Novartis, Applied Therapeutics, Amarin, and Eli Lilly. Dr. Martinez has received personal fees from AstraZeneca as honoraria for being an Executive Committee Member for DAPA-HF and has received research grants and/or honoraria from Novartis, AstraZeneca, Bayer, Pfizer, Bristol-Myers Squibb, Gador, Baliarda and Boehringer Ingelheim. Dr. O'Meara has received consultation and speaker fees being paid to the Montreal Heart Institute Research Center from Amgen, Merck, and Novartis; is receiving consultation and speaker fees from AstraZeneca, Bayer, and Boehringer Ingelheim; serving on a steering committee and as a national leader for clinical studies with fees paid to Montreal Heart Institute Research Center from American Regent, AstraZeneca, Cytokinetics, Merck, and Novartis; and clinical trial participation from Amgen, Abbott, American Regent, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Eidos, Novartis, Merck, Pfizer, and Sanofi. Dr. Nicolau has received speaker/consulting honoraria and/or research grant support from Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Esperion, CSL Behring, Dalcor, Daiichi-Sankyo, Janssen, GlaxoSmithKline, Merck, Novartis, Novo Nordisk, Pfizer, Sanofi, Servier and Vifor Pharma. Dr. Petrie has received research grants or consultancy fees from SQ Innovations, AstraZeneca, Roche, Boehringer Ingelheim, Eli Lilly, Napp Pharmaceuticals, Novartis, and Novo Nordisk; and has served on clinical events committees for AbbVie, Alnylam, Astra Zeneca, Bayer, Boehringer Ingelheim, GlaxoSmithKline, Resverlogix, and Novo Nordisk. Dr. Ponikowski was an investigator in the DAPA-HF trial; received personal fees from AstraZeneca for lectures and consultancy related to the trial; has participated in clinical trials and received research grants to his institute and personal fees for speakers bureau and consultancy from Vifor Pharma; participated in clinical trials and received personal fees for consultancy and speakers bureaus from Boehringer Ingelheim, Bayer, Bristol Myers Squibb, Cibiem, Novartis, and Renal Guard; and has received personal fees for speakers bureaus and consultancy from Servier and Respicardia, personal fees for speakers bureaus from Berlin-Chemie, and personal fees for lectures from Pfizer. Dr. Sabatine received grant support (paid to Brigham and Women’s Hospital), consulting fees from Amgen, AstraZeneca, Intarcia Therapeutics, Janssen Research and Development, the Medicines Company, MedImmune, Merck, Novartis Anthos Therapeutics, Bristol-Myers Squibb, CVS Caremark, DalCor Pharmaceuticals, Dyrnamix, Esperion, IFM Therapeutics, and Ionis Pharmaceuticals, and grant support (paid to Brigham and Woman’s Hospital) from Bayer, Daiichi Sankyo, Eisai, GlaxoSmithKline, Pfizer, Poxel, Quark Pharmaceuticals, and Takeda Pharmaceutical; and serving as a member of the TIMI Study Group, which receives grant support (paid to Brigham and Women’s Hospital) from Abbott, Aralez Pharmaceuticals, Roche, and Zora Biosciences. Dr. Schou has received grants from The Capital Region of Denmark and the Danish Heart Foundation; personal fees and nonfinancial support from AstraZeneca; and personal fees from Novo Nordisk and Boehringe. Publisher Copyright: © 2021

PY - 2021

Y1 - 2021

N2 - Objectives: The purpose of this study was to assess the efficacy and safety of dapagliflozin in patients taking or not taking an mineralocorticoid receptor antagonist (MRA) at baseline in the DAPA-HF (Dapagliflozin And Prevention of Adverse outcomes in Heart Failure) trial. Background: MRAs and sodium glucose co-transporter 2 inhibitors each have diuretic activity, lower blood pressure, and reduce glomerular filtration rate (GFR). Therefore, it is important to investigate the safety, as well as efficacy, of their combination. Methods: A total of 4,744 patients with heart failure with reduced ejection fraction (HFrEF) were randomized to placebo or dapagliflozin 10 mg daily. The efficacy of dapagliflozin on the primary composite outcome (cardiovascular death or episode of worsening heart failure) and its components was examined according to MRA use, as were predefined safety outcomes. Results: A total of 3,370 patients (71%) were treated with an MRA and they were younger (65 vs. 69 years of age), less often from North America (9% vs. 26%), had worse New York Heart Association functional class (35% vs. 25% in class III/IV), lower left ventricular ejection fraction (30.7% vs. 31.9%) and systolic blood pressure (120.3 vs. 125.5 mm Hg), but higher estimated GFR (67.1 vs. 62.6 ml/min/1.73 m2), than patients not taking an MRA. The benefit of dapagliflozin compared with placebo was similar in patients taking or not taking an MRA: hazard ratio: 0.74 (95% confidence interval [CI]: 0.63 to 0.87) versus 0.74 (95% CI: 0.57 to 0.95), respectively, for the primary endpoint (p value for interaction = 0.97); similar findings were observed for secondary endpoints. In both MRA subgroups, safety outcomes were similar in patients randomized to dapagliflozin or placebo. Conclusions: Dapagliflozin was similarly efficacious and safe in patients with HFrEF taking or not taking an MRA, supporting the use of both drugs together. (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)

AB - Objectives: The purpose of this study was to assess the efficacy and safety of dapagliflozin in patients taking or not taking an mineralocorticoid receptor antagonist (MRA) at baseline in the DAPA-HF (Dapagliflozin And Prevention of Adverse outcomes in Heart Failure) trial. Background: MRAs and sodium glucose co-transporter 2 inhibitors each have diuretic activity, lower blood pressure, and reduce glomerular filtration rate (GFR). Therefore, it is important to investigate the safety, as well as efficacy, of their combination. Methods: A total of 4,744 patients with heart failure with reduced ejection fraction (HFrEF) were randomized to placebo or dapagliflozin 10 mg daily. The efficacy of dapagliflozin on the primary composite outcome (cardiovascular death or episode of worsening heart failure) and its components was examined according to MRA use, as were predefined safety outcomes. Results: A total of 3,370 patients (71%) were treated with an MRA and they were younger (65 vs. 69 years of age), less often from North America (9% vs. 26%), had worse New York Heart Association functional class (35% vs. 25% in class III/IV), lower left ventricular ejection fraction (30.7% vs. 31.9%) and systolic blood pressure (120.3 vs. 125.5 mm Hg), but higher estimated GFR (67.1 vs. 62.6 ml/min/1.73 m2), than patients not taking an MRA. The benefit of dapagliflozin compared with placebo was similar in patients taking or not taking an MRA: hazard ratio: 0.74 (95% confidence interval [CI]: 0.63 to 0.87) versus 0.74 (95% CI: 0.57 to 0.95), respectively, for the primary endpoint (p value for interaction = 0.97); similar findings were observed for secondary endpoints. In both MRA subgroups, safety outcomes were similar in patients randomized to dapagliflozin or placebo. Conclusions: Dapagliflozin was similarly efficacious and safe in patients with HFrEF taking or not taking an MRA, supporting the use of both drugs together. (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)

KW - aldosterone

KW - dapagliflozin

KW - heart failure

KW - hyperkalemia

KW - kidney function

KW - mineralocorticoid receptor antagonist

KW - potassium

KW - SGLT2 inhibitor

U2 - 10.1016/j.jchf.2020.11.009

DO - 10.1016/j.jchf.2020.11.009

M3 - Journal article

C2 - 33549554

AN - SCOPUS:85101185054

VL - 9

SP - 254

EP - 264

JO - J A C C: Heart Failure

JF - J A C C: Heart Failure

SN - 2213-1779

IS - 4

ER -