Variation in renal function following transition to sacubitril/valsartan in patients with heart failure

Chatur, S. et al. (2023) Variation in renal function following transition to sacubitril/valsartan in patients with heart failure. Journal of the American College of Cardiology, 81(15), pp. 1443-1455. (doi: 10.1016/j.jacc.2023.02.009) (PMID:36812948)

Abstract

Background: Some patients with heart failure may experience transient changes in kidney function upon transition to sacubitril/valsartan. Whether such changes portend adverse outcomes or influence long-term treatment benefits with sacubitril/valsartan continuation is unknown. Objectives: To evaluate the association between the occurrence of moderate eGFR decline(>15%) after initial exposure to sacubitril/valsartan and subsequent cardiovascular outcomes and its treatment benefits in PARADIGM-HF and PARAGON-HF. Methods: In sequential run-in phases, patients were titrated to enalapril 10mg twice daily and then sacubitril/valsartan 97/103mg twice daily (in PARADIGM-HF) or valsartan 80mg twice daily and then sacubitril/valsartan 49/51mg twice daily (in PARAGON-HF). Results: Among randomized participants, 11% in PARADIGM-HF and 10% in PARAGON-HF experienced eGFR decline (>15%) during sacubitril/valsartan run-in. eGFR partially recovered(from nadir to post-randomization week 16) regardless of sacubitril/valsartan continuation or switch to RASi, post-randomization. Initial eGFR decline was not consistently associated with clinical outcomes in either trial. Treatment benefits of sacubitril/valsartan vs. RASi on primary outcomes were similar irrespective of run-in eGFR decline in PARADIGM-HF (eGFR decline: HR 0.69; 95%CI: 0.53-0.90 and no eGFR decline: HR 0.80; 95%CI: 0.73-0.88, Pinteraction=0.32) and PARAGON-HF (eGFR decline: RR 0.84; 95%CI 0.52-1.36 and no eGFR decline: RR 0.87; 95%CI: 0.75-1.02, Pinteraction=0.92). The treatment effect of sacubitril/valsartan remained consistent across a range of eGFR declines. Conclusion: Moderate eGFR decline when transitioning from RASi to sacubitril/valsartan is not consistently associated with adverse outcomes, and its long-term benefits are retained in heart failure across a broad range of eGFR declines. Early eGFR changes should not deter sacubitril/valsartan continuation or stall up-titration.

• Item Type: Articles
• Additional Information: PARADIGM-HF and PARAGON-HF were funded by Novartis Pharmaceuticals.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: McMurray, Professor John
• Authors: Chatur, S., Claggett, B. L., McCausland, F. R., Rouleau, J., Zile, M. R., Packer, M., Pfeffer, M. A., Lefkowitz, M., McMurray, J. J.V., Solomon, S. D., and Vaduganathan, M.
• 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: 20 February 2023
• Copyright Holders: Copyright © 2023 Elsevier on behalf of the American College of Cardiology Foundation
• First Published: First published in Journal of the American College of Cardiology 81(15): 1443-1455
• Publisher Policy: Reproduced under a Creative Commons License