Sacubitril/valsartan and loop diuretic requirement in heart failure with preserved ejection fraction in the PARAGON‐HF trial

Chatur, S., Claggett, B. L., Vardeny, O., Jering, K., Desai, A. S., Pfeffer, M. A., Lefkowitz, M., McMurray, J. J.V. , Solomon, S. D. and Vaduganathan, M. (2023) Sacubitril/valsartan and loop diuretic requirement in heart failure with preserved ejection fraction in the PARAGON‐HF trial. European Journal of Heart Failure, 25(1), pp. 87-94. (doi: 10.1002/ejhf.2703) (PMID:36181769)

Abstract

Aims: As sacubitril/valsartan may potentiate early natriuresis, expert consensus documents recommend diuretic dose reduction on first initiation. However, there are limited data on the effects of sacubitril/valsartan on the background of varying diuretic regimens or on diuretic requirements over time in HFpEF. Methods and Results: In this post hoc analysis of PARAGON-HF, of the 4,796 patients, background diuretic therapy was distributed as follows: 341(7%) on no diuretic, 698(15%) on non-loop diuretic, and 3,757(78%) were on loop diuretics (1,255, 1,589, and 913 were on <40mg, =40mg and >40mg furosemide equivalent doses, respectively). The primary composite outcome of total HF hospitalizations and CV death was analyzed using semiparametric proportional rates methods. The cumulative incidence of the primary composite outcome (first events) was lowest in patients on no diuretic and highest in those on >40mg of loop diuretic (P<0.001). The effects of sacubitril/valsartan (versus valsartan) on the primary composite outcome (recurrent events) did not significantly vary by baseline diuretic use (Pinteraction= 0.65). Treatment effects on safety outcomes were similar across diuretic categories. Sacubitril/valsartan reduced new loop diuretic initiations over the course of the trial (HR 0.83; 95% CI: 0.68-1.00, p=0.055), with similar mean loop diuretic dose and rates of diuretic discontinuation between treatment groups in follow-up. Patients randomized to sacubitril/valsartan experienced a slight early reduction in diuretic initiation or dose escalation at 30 days after initiation (net reduction 1.7%, p=0.02), but these differences were not sustained beyond this timepoint. Conclusions: Patients with HFpEF on higher baseline diuretic doses were at heightened risk of HF events, but similarly benefited from sacubitril/valsartan with a consistent safety profile across a range of diuretic doses. Initiation of sacubitril/valsartan was associated with modestly lower new loop diuretic requirement in follow-up.

• Item Type: Articles
• Additional Information: PARAGON-HF was funded by Novartis Pharmaceuticals.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: McMurray, Professor John
• Authors: Chatur, S., Claggett, B. L., Vardeny, O., Jering, K., Desai, A. S., 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: European Journal of Heart Failure
• Publisher: Wiley
• ISSN: 1388-9842
• ISSN (Online): 1879-0844
• Published Online: 01 October 2022
• Copyright Holders: Copyright © 2022 The Authors
• First Published: First published in European Journal of Heart Failure 25(1): 87-94
• Publisher Policy: Reproduced under a Creative Commons License