Effect of dapagliflozin in patients with HFrEF treated with sacubitril/valsartan: the DAPA-HF trial

Solomon, S. D. et al. (2020) Effect of dapagliflozin in patients with HFrEF treated with sacubitril/valsartan: the DAPA-HF trial. JACC: Heart Failure, 8(10), pp. 811-818. (doi: 10.1016/j.jchf.2020.04.008) (PMID:32653447)

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Abstract

Objectives: This study assessed the efficacy and safety of dapagliflozin in patients who were or were not taking sacubitril/valsartan at baseline in the DAPA-HF (Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure) trial. Background: Both the angiotensin receptor neprilysin-inhibitor sacubitril/valsartan and the sodium glucose co-transporter 2 inhibitor dapagliflozin reduced cardiovascular death and heart failure (HF) hospitalization in patients with HF with reduced ejection fraction (HFrEF). Whether either of these classes of drugs influences the effectiveness or safety of the other remains unknown. Methods: DAPA-HF was a 4,744 patient trial that compared dapagliflozin with placebo in patients with HFrEF. Patients were analyzed according to whether they were taking sacubitril/valsartan at randomization. The efficacy of dapagliflozin on the primary composite outcome (CV death or episode of worsening heart failure), its components, and all-cause death was examined according to sacubitril/valsartan and the interaction tested. Predefined safety outcomes were examined by sacubitril/valsartan group. Results: A total of 508 patients (10.7%) enrolled in DAPA-HF were treated with sacubitril/valsartan at baseline. Patients prescribed sacubitril/valsartan were more likely to be from North America or Europe, to have lower ejection fractions and systolic and diastolic blood pressures, but were similar with respect to age, New York Heart Association functional class, history of diabetes, and use of other evidence-based HF therapies. The benefit of dapagliflozin compared with placebo was similar in patients taking sacubitril/valsartan (hazard ratio: 0.75; 95% confidence interval 0.50 to 1.13) compared with those not taking sacubitril/valsartan (hazard ratio: 0.74; 95% confidence interval 0.65 to 0.86) for the primary endpoint of cardiovascular death or worsening HF; similar findings were observed for secondary endpoints. All measures of safety, including episodes related to hypovolemia, were similar among patients randomized to dapagliflozin or placebo, whether they received background sacubitril/valsartan. Conclusions: Dapagliflozin was similarly efficacious and safe in patients who were and who were not taking sacubitril/valsartan in the DAPA-HF trial, which suggested that the use of both agents together could further lower morbidity and mortality in patients with HFrEF. (Dapagliflozin And Prevention of Adverse outcomes in Heart Failure [DAPA-HF]; NCT03036124)

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Dewan, Dr Pooja and Jhund, Dr Pardeep and McMurray, Professor John and Kober, Professor Lars
Authors: Solomon, S. D., Jhund, P. S., Claggett, B. L., Dewan, P., Køber, L., Kosiborod, M. N., Martinez, F. A., Ponikowski, P., Sabatine, M. S., Inzucchi, S. E., Desai, A. S., Bengtsson, O., Lindholm, D., Sjostrand, M., Langkilde, A. M., and McMurray, J. J.V.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:JACC: Heart Failure
Publisher:Elsevier
ISSN:2213-1779
ISSN (Online):2213-1787
Published Online:08 July 2020
Copyright Holders:Copyright © 2020 American College of Cardiology Foundation
First Published:First published in JACC: Heart Failure 8(10): 811-818
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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