Efficacy of dapagliflozin according to geographic location of patients with heart failure

Kondo, T. et al. (2023) Efficacy of dapagliflozin according to geographic location of patients with heart failure. Journal of the American College of Cardiology, 82(10), pp. 1014-1026. (doi: 10.1016/j.jacc.2023.05.056) (PMID:37610398)

Abstract

Background: Because clinical characteristics and prognosis vary by geographic region in patients with heart failure (HF), the response to treatment may also vary. A previous report suggested that the efficacy of sodium-glucose cotransporter-2 inhibitor efficacy in heart failure with reduced ejection fraction (HFrEF) may be modified by region. Objectives: The goal of this study was to examine the efficacy and safety of dapagliflozin in patients with HF according to geographic region. Methods: We conducted a patient-level pooled analysis of the DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) and DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure) trials, which evaluated the effects of dapagliflozin in HFrEF and heart failure with mildly reduced ejection fraction (HFmrEF)/heart failure with preserved ejection fraction (HFpEF), respectively. The primary outcome was the composite of worsening HF or cardiovascular death. Results: Among 11,007 patients, 5,159 (46.9%) were enrolled in Europe, 1,528 (13.9%) in North America, 1,998 (18.2%) in South America, and 2,322 (21.1%) in Asia. The rate of the primary outcome (per 100 person-years) was higher in North America (13.9 [95% CI: 12.5-15.4]) than in other regions: Europe 10.8 (95% CI: 10.1-11.5), South America 10.0 (95% CI: 9.0-11.1), and Asia 10.5 (95% CI: 9.5-11.5). The benefit of dapagliflozin on the primary outcome was not modified by region: dapagliflozin vs placebo HR: Europe, 0.85 (95% CI: 0.75-0.96); North America, 0.75 (95% CI: 0.61-0.93); South America, 0.72 (95% CI: 0.58-0.89); and Asia, 0.74 (95% CI: 0.61-0.91) (P interaction = 0.40). This was the same when evaluated separately for HFrEF (P interaction = 0.39) and HFmrEF/HFpEF (P interaction = 0.84). Patients in North America discontinued randomized treatment more frequently than did those elsewhere (placebo discontinuation: 21.8% in North America vs 6.4% in South America), but discontinuation rates did not differ between placebo and dapagliflozin by region. Conclusions: The efficacy and safety of dapagliflozin were consistent across global regions despite geographic differences in patient characteristics, background treatment, and event rates.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Kondo, Dr Toru and Jhund, Professor Pardeep and Yang, Dr Mingming and McMurray, Professor John and Kober, Professor Lars
• Authors: Kondo, T., Wang, X., Yang, M., Jhund, P. S., Claggett, B. L., Vaduganathan, M., Hernandez, A. F., Lam, C. S. P., Inzucchi, S. E., Martinez, F. A., de Boer, R. A., Kosiborod, M. N., Desai, A. S., Køber, L., Ponikowski, P., Sabatine, M. S., Langkilde, A. M., Petersson, M., Zaozerska, N., Bachus, E., Solomon, S. D., and McMurray, J. J. V.
• 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: 21 August 2023
• Copyright Holders: Copyright © 2023 The Authors
• First Published: First published in Journal of the American College of Cardiology 82(10):1014-1026
• Publisher Policy: Reproduced under a Creative Commons license

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	SCMH - Cardiovascular & Metabolic Health