Estimated event-free survival benefits with dapagliflozin in HF with mildly reduced or preserved ejection fraction

Vaduganathan, M. et al. (2022) Estimated event-free survival benefits with dapagliflozin in HF with mildly reduced or preserved ejection fraction. Journal of the American College of Cardiology, 80(19), pp. 1775-1784. (doi: 10.1016/j.jacc.2022.08.745) (PMID:36041669)

Abstract

Background: Recent guidelines support consideration of sodium glucose co-transporter(SGLT)-2 inhibitors in the long-term management of heart failure (HF) with mildly reduced or preserved ejection fraction. Patients and clinicians may be interested in the expected lifetime benefits of SGLT-2 inhibitors. Objectives: To estimate event-free survival gains from long-term use of dapagliflozin in patients with HF with mildly reduced or preserved ejection fraction overall and in clinically relevant subgroups. Methods: In this pre-specified analysis of DELIVER, we applied validated nonparametric age-based methods to extrapolate potential gains in survival free from the primary endpoint (cardiovascular death or worsening HF event) from long-term use of dapagliflozin. Eligible participants had symptomatic HF, LVEF>40%, elevated natriuretic peptide levels, and structural heart disease. For every year between age 55 and 85, we estimated event-free survival using age at randomization rather than time from randomization as the time horizon. Residual lifespan free from primary endpoint was estimated based on area under the survival curve in each arm. Results: Among 6,263 participants, mean survival free from the primary endpoint for a 65-year-old participant was 12.1 (95%CI 11.0 to 13.2) years with dapagliflozin and 9.7 (95%CI 8.8 to 10.7) years with placebo, representing a 2.3 (95%CI 0.9 to 3.8) year event-free survival gain(P=0.002). Treatment gains in survival free from the primary endpoint ranged from 2.0 (95%CI -0.6 to 4.6) years in a 55-year-old to 1.2 (95%CI -0.1 to 2.4) years in a 75-year-old. Mean event-free survival was greater with dapagliflozin than with placebo across all 14 subgroups. Conclusions: Treatment with dapagliflozin is projected to extend event-free survival by up to 2-2.5 years among middle age and older individuals with HF with mildly reduced, preserved, or improved ejection fraction.

• Item Type: Articles
• Additional Information: The DELIVER trial was funded by AstraZeneca.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Jhund, Professor Pardeep and McMurray, Professor John
• Authors: Vaduganathan, M., Claggett, B. L., Jhund, P., de Boer, R. A., Hernandez, A. F., Inzucchi, S. E., Kosiborod, M. N., Lam, C. S.P., Martinez, F., Shah, S. J., Desai, A. S., Lindholm, D., Petersson, M., Langkilde, A. M., McMurray, J. J.V., and Solomon, S. D.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Journal of the American College of Cardiology
• Publisher: Elsevier
• ISSN: 0735-1097
• ISSN (Online): 1558-3597
• Published Online: 27 August 2022
• Copyright Holders: Copyright © 2022 The Authors
• First Published: First published in Journal of the American College of Cardiology 80(19): 1775-1784
• Publisher Policy: Reproduced under a Creative Commons License