Effect of sacubitril/valsartan versus enalapril on changes in heart failure therapies over time: the PARADIGM‐HF trial

Bhatt, A. S. et al. (2021) Effect of sacubitril/valsartan versus enalapril on changes in heart failure therapies over time: the PARADIGM‐HF trial. European Journal of Heart Failure, 23(9), pp. 1518-1524. (doi: 10.1002/ejhf.2259) (PMID:34101308)

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Background: Sacubitril/valsartan improves morbidity and mortality in patients with heart failure and reduced ejection fraction (HFrEF). Whether initiation of sacubitril/valsartan limits the use and dosing of other elements of guideline-directed medical therapy (GDMT) for HFrEF is unknown. We examined the effects of sacubitril/valsartan, compared with enalapril, on β-blocker and MRA use and dosing in a large randomized clinical trial. Methods: Patients with full data on medication/dose use were included. We examined β-blocker and MRA use/dose in patients randomized to sacubitril/valsartan versus enalapril through 12-month follow-up. New initiations and discontinuations of β-blocker and MRA were compared between treatment groups. Results: Overall, 8398 (99.9%) had full medication and dose data at baseline. Baseline use of β-blocker and MRA at any dose was 87.1% and 55%, respectively. Mean doses of β-blocker and MRA were similar between treatment groups at baseline and at 6-months and 12-months follow-up. New initiations through 12-months follow-up were infrequent and similar in the sacubitril/valsartan and enalapril groups for β-blockers (37 [9.0%] vs. 42 [10.2%], p = 0.56) and MRA (127 [7.6%] vs. 143 [9.2%], p = 0.10). Among patients on MRA therapy at baseline (n = 4634), there were fewer MRA discontinuations in patients on sacubitril/valsartan as compared with enalapril at 12-months (125 [6.2%] vs. 187 [9.0%], p = 0.001). Discontinuations of β-blockers were not significantly different between groups in follow-up (2.2% vs 2.6%, p = 0.26). Conclusions: Initiation of sacubitril/valsartan, even when titrated to target dose, did not appear to lead to greater discontinuation or dose downtitrations of other key guideline-directed medical therapies, and was associated with fewer discontinuations of MRA. Use of sacubitril/valsartan (when compared with enalapril) may promote sustained MRA use in follow-up.

Item Type:Articles
Additional Information:The PARADIGM-HF trial was funded by Novartis AG.
Glasgow Author(s) Enlighten ID:McMurray, Professor John
Authors: Bhatt, A. S., Vaduganathan, M., Claggett, B. L., Liu, J., Packer, M., Desai, A. S., Lefkowitz, M. P., Rouleau, J. L., Shi, V. C., Zile, M. R., Swedberg, K., Vardeny, O., McMurray, J. J.V., and Solomon, S. D.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:European Journal of Heart Failure
ISSN (Online):1879-0844
Published Online:07 June 2021
Copyright Holders:Copyright © 2021 The Authors
First Published:First published in European Journal of Heart Failure 23(9): 1518-1524
Publisher Policy:Reproduced under a Creative Commons License

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