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

AIMS: 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 for HFrEF is unknown. We examined the effects of sacubitril/valsartan, compared with enalapril, on β‐blocker and mineralocorticoid receptor antagonist (MRA) use and dosing in a large randomized clinical trial. METHODS AND RESULTS: Patients with full data on medication use were included. We examined β‐blocker and MRA use in patients randomized to sacubitril/valsartan vs. enalapril through 12‐month follow‐up. New initiations and discontinuations of β‐blocker and MRA were compared between treatment groups. Overall, 8398 (99.9%) had full medication and dose data at baseline. Baseline use of β‐blocker and MRA at any dose was 87% and 56%, respectively. Mean doses of β‐blocker and MRA were similar between treatment groups at baseline and at 6‐month and 12‐month follow‐up. New initiations through 12‐month 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, 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 down‐titration 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.