Sex differences in characteristics, outcomes and treatment response with dapagliflozin across the range of ejection fraction in patients with heart failure: insights from DAPA-HF and DELIVER

Wang, X. et al. (2023) Sex differences in characteristics, outcomes and treatment response with dapagliflozin across the range of ejection fraction in patients with heart failure: insights from DAPA-HF and DELIVER. Circulation, 147(8), pp. 624-634. (doi: 10.1161/CIRCULATIONAHA.122.062832) (PMID:36342789) (PMCID:PMC9974767)

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Abstract

Background: Sodium-glucose cotransporter-2 (SGLT2) inhibitors have emerged as a key pharmacotherapy in heart failure (HF) with both reduced and preserved ejection fraction. The benefit of other HF therapies may be modified by sex, but whether sex modifies the treatment effect and safety profile of SGLT2 inhibitors remains unclear. Our analyses aim to assess the impact of sex on the efficacy and safety of dapagliflozin. Methods: In a pre-specified patient-level pooled analysis of DAPA-HF and DELIVER, clinical outcomes were compared by sex (including the composite of cardiovascular [CV] death or worsening HF events; CV death; all-cause death, total events (first and recurrent HF hospitalization and CV death), and Kansas City Cardiomyopathy Questionnaire [KCCQ] scores) across the spectrum of left ventricular ejection fraction (EF). Results: Of a total of 11,007 randomized patients, 3856 (35%) were women. Women with HF were older, had higher body mass index, but were less likely to have a history of diabetes and myocardial infarction/stroke; and more likely to have hypertension and atrial fibrillation, compared to men. At baseline, women had higher EF but worse KCCQ scores than men. After adjusting for baseline differences, women were less likely than men to experience CV death (adjusted hazard ratio [aHR] 0.69, 95% CI 0.60-0.79), all-cause death (aHR 0.69, 95% 0.62-0.78), HF hospitalizations (aHR 0.82, 95% CI 0.72-0.94), and total events (adjusted rate ratio 0.77, 95% CI 0.71-0.84). Dapagliflozin reduced the primary endpoint in both men and women similarly (p-interaction=0.77) with no sex-related differences in secondary outcomes (all p-interactions > 0.35) or safety events. The benefit of dapagliflozin was observed across the entire EF spectrum and was not modified by sex (p-interaction > 0.40). There were no sex-related differences in serious adverse events, adverse events, or drug discontinuation due to adverse events. Conclusions: In DAPA-HF and DELIVER, the response to dapagliflozin was similar between men and women. Sex did not modify the treatment effect of dapagliflozin across the range of ejection fraction.

Item Type:Articles
Additional Information:AstraZeneca was the sponsor and funder of the DAPA-HF and DELIVER trials. Dr. Wang is supported by a T32 postdoctoral training grant from the National Heart, Lung, and Blood Institute (T32 HL094301), and by the Scott Schoen and Nancy Adams First.In.Women Cardiovascular Fellowship, Mary Horrigan Connors Center for Women’s Health and Gender Biology at Brigham and Women’s Hospital Dr. Pabon is supported by John S. LaDue Memorial Fellowship at Harvard Medical School, and by the Scott Schoen and Nancy Adams First.In.Women Cardiovascular Fellowship, Mary Horrigan Connors Center for Women’s Health and Gender Biology at Brigham and Women’s Hospital. Dr. Shah is supported by research grants from the National Institutes of Health (U54 HL160273, R01 HL140731, R01 HL149423) Dr. Lam is supported by a Clinician Scientist Award from the National Medical Research Council of Singapore. Dr. McMurray is supported by a British Heart Foundation Centre of Research Excellence Grant RE/18/6/34217.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Jhund, Professor Pardeep and McMurray, Professor John and Kober, Professor Lars
Authors: Wang, X., Vaduganathan, M., Claggett, B. L., Hegde, S. M., Pabon, M., Kulac, I. J., Vardeny, O., O'Meara, E., Zieroth, S., Katova, T., McGrath, M. M., Pouleur, A.-C., Jhund, P. S., Desai, A. S., Inzucchi, S. E., Kosiborod, M. N., de Boer, R. A., Køber, L., Sabatine, M. S., Martinez, F. A., Ponikowski, P., Shah, S. J., Hernandez, A. F., Langkilde, A. M., McMurray, J. J.V., Solomon, S. D., and Lam, C. S.P.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:Circulation
Publisher:American Heart Association
ISSN:0009-7322
ISSN (Online):1524-4539
Published Online:07 November 2022
Copyright Holders:Copyright © 2022 The Authors
First Published:First published in Circulation 147(8): 624-634
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
303944BHF Centre of ExcellenceColin BerryBritish Heart Foundation (BHF)RE/18/6/34217CAMS - Cardiovascular Science