Jawad H Butt1, Kieran F Docherty2, Mark C Petrie2, Morten Schou3, Mikhail N Kosiborod4,5, Eileen O'Meara6, Tzvetana Katova7, Charlotta E A Ljungman8, Mirta Diez9, Modele O Ogunniyi10, Anna Maria Langkilde11, Mikaela Sjöstrand11, Daniel Lindholm11, Olof Bengtsson11, Felipe A Martinez12, Piotr Ponikowski13, Marc S Sabatine14, Scott D Solomon15, Pardeep S Jhund2, John J V McMurray2, Lars Køber1. 1. Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. 2. BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland. 3. Department of Cardiology, Herlev-Gentofte University Hospital, Herlev, Denmark. 4. St Luke's Mid America Heart Institute, University of Missouri-Kansas City. 5. The George Institute for Global Health, University of New South Wales, Sydney, Australia. 6. Department of Cardiology, Montreal Heart Institute, Montreal, Ontario, Canada. 7. Clinic of Cardiology, National Cardiology Hospital, Sofia, Bulgaria. 8. Department of Molecular and Clinical Medicine and Cardiology, Sahlgrenska Academy, Gothenburg, Sweden. 9. Division of Cardiology, Institute Cardiovascular de Buenos Aires, Buenos Aires, Argentina. 10. Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia. 11. Late Stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden. 12. Universidad Nacional de Córdoba, Córdoba, Argentina. 13. Center for Heart Diseases, University Hospital, Wroclaw Medical University, Wrocław, Poland. 14. TIMI Study Group, Brigham and Women's Hospital, Boston, Massachusetts. 15. Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
Abstract
Importance: Women may respond differently to certain treatments for heart failure (HF) with reduced ejection fraction (HFrEF) than men. Objective: To investigate the efficacy and safety of dapagliflozin compared with placebo in men and women with HFrEF enrolled in the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure trial (DAPA-HF). Design, Setting, and Participants: Prespecified subgroup analysis of a phase 3 randomized clinical trial conducted at 410 sites in 20 countries. Patients with New York Heart Association functional class II through IV with an ejection fraction of 40% or less and elevated N-terminal pro-B-type natriuretic peptide were eligible. Data were analyzed between June 2020 and January 2021. Interventions: Addition of once-daily 10 mg of dapagliflozin or placebo to guideline-recommended therapy. Main Outcomes and Measures: The primary outcome was the composite of an episode of worsening HF (HF hospitalization or urgent HF visit requiring intravenous therapy) or cardiovascular death. Results: A total of 4744 patients were randomized in DAPA-HF, of whom 1109 were women (23.4%). Compared with placebo, dapagliflozin reduced the risk of worsening HF events or cardiovascular death to a similar extent in both men and women (hazard ratios, 0.73 [95% CI, 0.63-0.85] and 0.79 [95% CI, 0.59-1.06], respectively; P for interaction = .67). Consistent benefits were observed for the components of the primary outcome and all-cause mortality. Compared with placebo, dapagliflozin increased the proportion of patients with a meaningful improvement in symptoms (Kansas City Cardiomyopathy Questionnaire total symptom score of ≥5 points; men, 59% vs 50%; women, 57% vs 54%; P for interaction = .14) and decreased the proportion with worsening symptoms (Kansas City Cardiomyopathy Questionnaire total symptom score decrease of ≥5 points; men, 25% vs 34%; women, 27% vs 31%; P for interaction = .15), irrespective of sex. Results were consistent for the Kansas City Cardiomyopathy Questionnaire clinical summary score and overall summary score. Study drug discontinuation and serious adverse events were not more frequent in the dapagliflozin group than in the placebo group in either men or women. Conclusions and Relevance: Dapagliflozin reduced the risk of worsening HF, cardiovascular death, and all-cause death and improved symptoms, physical function, and health-related quality of life similarly in men and women with heart failure and reduced ejection fraction. In addition, dapagliflozin was safe and well-tolerated irrespective of sex. Trial Registration: ClinicalTrials.gov Identifier: NCT03036124.
Importance: Women may respond differently to certain treatments for heart failure (HF) with reduced ejection fraction (HFrEF) than men. Objective: To investigate the efficacy and safety of dapagliflozin compared with placebo in men and women with HFrEF enrolled in the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure trial (DAPA-HF). Design, Setting, and Participants: Prespecified subgroup analysis of a phase 3 randomized clinical trial conducted at 410 sites in 20 countries. Patients with New York Heart Association functional class II through IV with an ejection fraction of 40% or less and elevated N-terminal pro-B-type natriuretic peptide were eligible. Data were analyzed between June 2020 and January 2021. Interventions: Addition of once-daily 10 mg of dapagliflozin or placebo to guideline-recommended therapy. Main Outcomes and Measures: The primary outcome was the composite of an episode of worsening HF (HF hospitalization or urgent HF visit requiring intravenous therapy) or cardiovascular death. Results: A total of 4744 patients were randomized in DAPA-HF, of whom 1109 were women (23.4%). Compared with placebo, dapagliflozin reduced the risk of worsening HF events or cardiovascular death to a similar extent in both men and women (hazard ratios, 0.73 [95% CI, 0.63-0.85] and 0.79 [95% CI, 0.59-1.06], respectively; P for interaction = .67). Consistent benefits were observed for the components of the primary outcome and all-cause mortality. Compared with placebo, dapagliflozin increased the proportion of patients with a meaningful improvement in symptoms (Kansas City Cardiomyopathy Questionnaire total symptom score of ≥5 points; men, 59% vs 50%; women, 57% vs 54%; P for interaction = .14) and decreased the proportion with worsening symptoms (Kansas City Cardiomyopathy Questionnaire total symptom score decrease of ≥5 points; men, 25% vs 34%; women, 27% vs 31%; P for interaction = .15), irrespective of sex. Results were consistent for the Kansas City Cardiomyopathy Questionnaire clinical summary score and overall summary score. Study drug discontinuation and serious adverse events were not more frequent in the dapagliflozin group than in the placebo group in either men or women. Conclusions and Relevance: Dapagliflozin reduced the risk of worsening HF, cardiovascular death, and all-cause death and improved symptoms, physical function, and health-related quality of life similarly in men and women with heart failure and reduced ejection fraction. In addition, dapagliflozin was safe and well-tolerated irrespective of sex. Trial Registration: ClinicalTrials.gov Identifier: NCT03036124.
Authors: María Ascensión Sanromán Guerrero; Sonia Antoñana Ugalde; Elena Hernández Sánchez; Susana Del Prado Díaz; Marta Jiménez-Blanco Bravo; David Cordero Pereda; José Luis Zamorano Gómez; Jesús Álvarez-García Journal: Front Cardiovasc Med Date: 2022-07-25
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