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

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.