Efficacy and safety of dapagliflozin in heart failure with reduced ejection fraction according to N-terminal pro-B-type natriuretic peptide: insights from the DAPA-HF trial

Butt, J. H. et al. (2021) Efficacy and safety of dapagliflozin in heart failure with reduced ejection fraction according to N-terminal pro-B-type natriuretic peptide: insights from the DAPA-HF trial. Circulation: Heart Failure, 14(12), e008837. (doi: 10.1161/CIRCHEARTFAILURE.121.008837) (PMID:34802253)

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Background: Effective therapies for HFrEF usually reduce NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels, and it is important to establish whether new treatments are effective across the range of NT-proBNP. Methods: We evaluated both these questions in the DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) trial. Patients in New York Heart Association functional class II to IV with a left ventricular ejection fraction ≤40% and a NT-proBNP level ≥600 pg/mL (≥600 ng/L; ≥400 pg/mL if hospitalized for HF within the previous 12 months or ≥900 pg/mL if atrial fibrillation/flutter) were eligible. The primary outcome was the composite of an episode of worsening HF or cardiovascular death. Results: Of the 4744 randomized patients, 4742 had an available baseline NT-proBNP measurement (median, 1437 pg/mL [interquartile range, 857–2650 pg/mL]). Compared with placebo, treatment with dapagliflozin significantly reduced NT-proBNP from baseline to 8 months (absolute least-squares mean reduction, −303 pg/mL [95% CI, −457 to −150 pg/mL]; geometric mean ratio, 0.92 [95% CI, 0.88–0.96]). Dapagliflozin reduced the risk of worsening HF or cardiovascular death, irrespective of baseline NT-proBNP quartile; the hazard ratio for dapagliflozin versus placebo, from lowest to highest quartile was 0.43 (95% CI, 0.27–0.67), 0.77 (0.56–1.04), 0.78 (0.60–1.01), and 0.78 (0.64–0.95); P for interaction=0.09. Consistent benefits were observed for all-cause mortality. Compared with placebo, dapagliflozin increased the proportion of patients with a meaningful improvement (≥5 points) in Kansas City Cardiomyopathy Questionnaire total symptom score ( P for interaction=0.99) and decreased the proportion with a deterioration ≥5 points ( P for interaction=0.87) across baseline NT-proBNP quartiles. Conclusions: In patients with HFrEF, dapagliflozin reduced NT-proBNP by 300 pg/mL after 8 months of treatment compared with placebo. In addition, dapagliflozin reduced the risk of worsening HF and death, and improved symptoms, across the spectrum of baseline NT-proBNP levels included in DAPA-HF. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03036124.

Item Type:Articles
Additional Information:The DAPA-HF trial was funded by AstraZeneca. Dr McMurray was supported by a British Heart Foundation Centre of Research Excellence Grant RE/18//34217.
Glasgow Author(s) Enlighten ID:Adamson, Dr Carly and Butt, Mr Jawad and Docherty, Dr Kieran and Jhund, Professor Pardeep and Kober, Professor Lars and McMurray, Professor John and Petrie, Professor Mark
Authors: Butt, J. H., Adamson, C., Docherty, K. F., de Boer, R. A., Petrie, M. C., Inzucchi, S. E., Kosiborod, M. N., Maria Langkilde, A., Lindholm, D., Martinez, F. A., Bengtsson, O., Schou, M., O’Meara, E., Ponikowski, P., Sabatine, M. S., Sjöstrand, M., Solomon, S. D., Jhund, P. S., McMurray, J. J.V., and Køber, L.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:Circulation: Heart Failure
Publisher:American Heart Association
ISSN (Online):1941-3297
Published Online:22 November 2021
Copyright Holders:Copyright © 2021 American Heart Association, Inc.
First Published:First published in Circulation: Heart Failure 14(12): e008837
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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