Dosing of losartan in men vs. women with HFrEF: the HEAAL trial

Ferreira, J. P. et al. (2021) Dosing of losartan in men vs. women with HFrEF: the HEAAL trial. European Journal of Heart Failure, 23(9), pp. 1477-1484. (doi: 10.1002/ejhf.2255) (PMID:34050594)

Abstract

Background: In heart failure with reduced ejection fraction (HFrEF), guidelines recommend up-titration of angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptors blockers (ARBs) to the maximum tolerated dose. However, some studies suggest that women might need lower doses of ACEi/ARBs than men to achieve similar treatment benefit. Methods: The HEAAL trial compared low vs. high dose of losartan. We reassessed the efficacy and safety of high- vs. low-dose in men vs. women using Cox models and Machine Learning algorithms. Results: The mean age was 66 years and 30% of the patients were women. Men appeared to have benefited more from high-dose than from low-dose losartan, whereas women appeared to have responded similarly to low and high doses: HR (95%CI) comparing high- vs- low-dose losartan for the composite outcome of all-cause death or all-cause hospitalisation was 0.89 (0.81-0.98) in men and 1.10 (0.95-1.28) in women, interaction P=0.018. Female sex clustered along with older age, ischemic HF, NYHA III/IV, and eGFR<60 ml/min. Patients with these features had a poorer response to high-dose losartan. Subgroup analyses supported no benefit from high-dose losartan in patients with poorer kidney function and severe HF symptoms. Conclusions: Compared with men, women might need lower doses of losartan to achieve similar treatment benefit. However, beyond sex, other factors (e.g., kidney function, age, and symptoms) may influence the response to high-dose losartan, suggesting that sex-based subgroup findings may be biased by other confounders.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: McMurray, Professor John
• Authors: Ferreira, J. P., Konstam, M. A., McMurray, J. J.V., Butler, J., Girerd, N., Rossignol, P., Sharma, A., Voors, A. A., Lam, C. S.P., Packer, M., and Zannad, F.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: European Journal of Heart Failure
• Publisher: Wiley
• ISSN: 1388-9842
• ISSN (Online): 1879-0844
• Published Online: 29 May 2021
• Copyright Holders: Copyright © 2021 European Society of Cardiology
• First Published: First published in European Journal of Heart Failure 23(9): 1477-1484
• Publisher Policy: Reproduced in accordance with the publisher copyright policy