Felipe A Martinez1, Matteo Serenelli2,3, Jose C Nicolau4, Mark C Petrie2, Chern-En Chiang5, Sergey Tereshchenko6, Scott D Solomon7, Silvio E Inzucchi8, Lars Køber9, Mikhail N Kosiborod10,11, Piotr Ponikowski12, Marc S Sabatine13, David L DeMets14, Monika Dutkiewicz-Piasecka15, Olof Bengtsson16, Mikaela Sjöstrand16, Anna Maria Langkilde16, Pardeep S Jhund2, John J V McMurray2. 1. Universidad Nacional de Córdoba, Argentina (F.M.). 2. BHF Cardiovascular Research Centre, University of Glasgow, UK (M. Serenelli, M.C.P., P.J., J.J.V.M.). 3. Cardiovascular Institute, Azienda Ospedaliero-Universitaria di Ferrara, Cona, Italy (M. Serenelli). 4. Instituto do Coracao (InCor), Hospital das Clínicas Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil (J.C.N.). 5. General Clinical Research Center and Division of Cardiology, Taipei Veterans General Hospital and National Yang-Ming University, Taiwan (C.E.-C.). 6. Department of Myocardial Disease and Heart Failure, National Medical Research Center of Cardiology of Russia, Moscow (S.T.). 7. Division of Cardiovascular Medicine (S.D.S.), Brigham and Women's Hospital, Boston, MA. 8. Section of Endocrinology, Yale School of Medicine, New Haven, CT (S.E.I.). 9. Department of Cardiology, Rigshospitalet Copenhagen University Hospital, Denmark (L.K.). 10. Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City (M.N.K.). 11. The George Institute for Global Health, University of New South Wales, Sydney, Australia (M.N.K.). 12. Center for Heart Diseases, University Hospital, Wroclaw Medical University, Poland (P.P.). 13. TIMI Study Group (M.S.S.), Brigham and Women's Hospital, Boston, MA. 14. Department of Biostatistics and Medical Informatics, University of Wisconsin, Madison (D.L.D.). 15. Late Stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Warsaw, Poland (M.D.-P.). 16. Late Stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden (O.B., M. Söjstrand, A.M.L.).
Abstract
BACKGROUND: The DAPA-HF trial (Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure) showed that dapagliflozin added to other guideline-recommended therapies reduced the risk of mortality and heart failure hospitalization and improved symptoms in patients with heart failure and reduced ejection fraction. We examined the effects of dapagliflozinaccording to age, given potential concerns about the efficacy and safety of therapies in the elderly. METHODS:Patients in New York Heart Association functional class II or greater with a left ventricular ejection fraction ≤40% and a modest elevation of NT-proBNP (N-terminal pro-B-type natriuretic peptide) were eligible. Key exclusion criteria included systolic blood pressure <95 mm Hg and estimated glomerular filtration rate <30 mL·min-1·1.73 m-2. The primary outcome was the composite of an episode of worsening heart failure (heart failure hospitalization or urgent heart failure visit) or cardiovascular death, whichever occurred first. RESULTS: A total of 4744 patients 22 to 94 years of age (mean age, 66.3 [SD 10.9] years) were randomized: 636 patients (13.4%) were <55 years of age, 1242 (26.2%) were 55 to 64 years of age, 1717 (36.2%) were 65 to 74 years of age, and 1149 (24.2%) were ≥75 years of age. The rate of the primary outcome (per 100 person-years, placebo arm) in each age group was 13.6 (95% CI, 10.4-17.9), 15.7 (95% CI, 13.2-18.7), 15.1 (95% CI, 13.1-17.5), and 18.0 (95% CI, 15.2-21.4) with corresponding dapagliflozin/placebo hazard ratios of 0.87 (95% CI, 0.60-1.28), 0.71 (95% CI, 0.55-0.93), 0.76 (95% CI, 0.61-0.95), and 0.68 (95% CI, 0.53-0.88; P for interaction=0.76). Consistent benefits were observed for the components of the primary outcome, all-cause mortality, and symptoms. Although adverse events and study drug discontinuation increased with age, neither was significantly more common with dapagliflozin in any age group. CONCLUSIONS:Dapagliflozin reduced the risk of death and worsening heart failure and improved symptoms across the broad spectrum of age studied in DAPA-HF. There was no significant imbalance in tolerability or safety events between dapagliflozin and placebo, even in elderly individuals. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03036124.
RCT Entities:
BACKGROUND: The DAPA-HF trial (Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure) showed that dapagliflozin added to other guideline-recommended therapies reduced the risk of mortality and heart failure hospitalization and improved symptoms in patients with heart failure and reduced ejection fraction. We examined the effects of dapagliflozin according to age, given potential concerns about the efficacy and safety of therapies in the elderly. METHODS:Patients in New York Heart Association functional class II or greater with a left ventricular ejection fraction ≤40% and a modest elevation of NT-proBNP (N-terminal pro-B-type natriuretic peptide) were eligible. Key exclusion criteria included systolic blood pressure <95 mm Hg and estimated glomerular filtration rate <30 mL·min-1·1.73 m-2. The primary outcome was the composite of an episode of worsening heart failure (heart failure hospitalization or urgent heart failure visit) or cardiovascular death, whichever occurred first. RESULTS: A total of 4744 patients 22 to 94 years of age (mean age, 66.3 [SD 10.9] years) were randomized: 636 patients (13.4%) were <55 years of age, 1242 (26.2%) were 55 to 64 years of age, 1717 (36.2%) were 65 to 74 years of age, and 1149 (24.2%) were ≥75 years of age. The rate of the primary outcome (per 100 person-years, placebo arm) in each age group was 13.6 (95% CI, 10.4-17.9), 15.7 (95% CI, 13.2-18.7), 15.1 (95% CI, 13.1-17.5), and 18.0 (95% CI, 15.2-21.4) with corresponding dapagliflozin/placebo hazard ratios of 0.87 (95% CI, 0.60-1.28), 0.71 (95% CI, 0.55-0.93), 0.76 (95% CI, 0.61-0.95), and 0.68 (95% CI, 0.53-0.88; P for interaction=0.76). Consistent benefits were observed for the components of the primary outcome, all-cause mortality, and symptoms. Although adverse events and study drug discontinuation increased with age, neither was significantly more common with dapagliflozin in any age group. CONCLUSIONS:Dapagliflozin reduced the risk of death and worsening heart failure and improved symptoms across the broad spectrum of age studied in DAPA-HF. There was no significant imbalance in tolerability or safety events between dapagliflozin and placebo, even in elderly individuals. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03036124.
Authors: Jennifer Cautela; Jean-Michel Tartiere; Alain Cohen-Solal; Anne Bellemain-Appaix; Alexis Theron; Thierry Tibi; James L Januzzi; François Roubille; Nicolas Girerd Journal: Eur J Heart Fail Date: 2020-04-30 Impact factor: 15.534
Authors: Kieran F Docherty; Pardeep S Jhund; Brian Claggett; João Pedro Ferreira; Olof Bengtsson; Silvio E Inzucchi; Lars Køber; Mikhail N Kosiborod; Anna Maria Langkilde; Felipe A Martinez; Piotr Ponikowski; Marc S Sabatine; Mikaela Sjöstrand; Scott D Solomon; John J V McMurray Journal: JAMA Cardiol Date: 2021-11-01 Impact factor: 30.154