Effects of dapagliflozin according to the heart failure collaboratory medical therapy score insights from DAPA-HF

Butt, J. H. et al. (2022) Effects of dapagliflozin according to the heart failure collaboratory medical therapy score insights from DAPA-HF. JACC: Heart Failure, 10(8), pp. 543-555. (doi: 10.1016/j.jchf.2022.03.009) (PMID:35902157)

Abstract

Background: The Heart Failure Collaboratory (HFC) has developed a score integrating classes and doses of guideline-directed medical therapies prescribed for patients with heart failure (HF) and reduced ejection fraction. One potential use of this score is to test whether new treatments demonstrate incremental benefits, even in patients receiving comprehensive guideline-directed medical therapy. Objectives The authors investigated the efficacy of dapagliflozin according to a modified HFC score in the DAPA-HF (Dapagliflozin And Prevention of Adverse outcomes in Heart Failure) trial. Methods: In DAPA-HF, 4,744 patients with HF and reduced ejection fraction were randomized to dapagliflozin or placebo. The modified HFC score accounted for race and electrocardiogram rhythm and rate, with a maximum possible score of 100%. The primary outcome was the composite of worsening HF or cardiovascular death. Results: The median modified HFC score was 50% (IQR: 27.5%-62.5%; range 0%-100%). Compared with the lowest tertile, the highest tertile of the treatment score was associated with a lower risk of worsening HF or cardiovascular death (tertile 1, reference; tertile 2, HR: 0.97 [95% CI: 0.82-1.14]; tertile 3, HR: 0.83 [95% CI: 0.70-0.99]). Dapagliflozin reduced the risk of worsening HF or cardiovascular death, irrespective of treatment score (the HRs for dapagliflozin vs placebo from tertile 1 to 3 were: 0.76 [95% CI: 0.61-0.94], 0.76 [95% CI: 0.60-0.97], and 0.71 [95% CI: 0.55-0.90]), respectively; Pinteraction = 0.89). Consistent benefits were observed for HF hospitalization, cardiovascular death, all-cause mortality, and improvement in the Kansas City Cardiomyopathy Questionnaire total symptom score (KCCQ-TTS). Conclusions: Dapagliflozin, compared with placebo, improved all outcomes examined, regardless of the modified HFC score. This score can be easily calculated in clinical trials and used to evaluate the incremental effects of new treatments. (Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure [DAPA-HF]; NCT03036124).

• Item Type: Articles
• Additional Information: The DAPA-HF trial was funded by AstraZeneca. Prof. McMurray is supported by British Heart Foundation Centre of Research Excellence Grant RE/18/6/34217.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Butt, Mr Jawad and Docherty, Dr Kieran and Jhund, Professor Pardeep and Dewan, Dr Pooja and McMurray, Professor John and Kober, Professor Lars
• Authors: Butt, J. H., Dewan, P., DeFilippis, E. M., Biering-Sørensen, T., Docherty, K. F., Jhund, P. S., Kosiborod, M. N., Martinez, F. A., Bengtsson, O., Johansen, N. D., Langkilde, A. M., Sjöstrand, M., Vaduganathan, M., Solomon, S. D., Sabatine, M. S., Køber, L., Fiuzat, 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 June 2022
• Copyright Holders: Copyright © 2022 Elsevier
• First Published: First published in JACC: Heart Failure 10(8):543-555
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
303944		BHF Centre of Excellence	Colin Berry	British Heart Foundation (BHF)	RE/18/6/34217	CAMS - Cardiovascular Science