Clinical practice guidelines support sustained use of renin-angiotensin-aldosterone-system (RAAS) inhibitors over time in heart failure with reduced ejection fraction, yet few data are available regarding frequency, timing, and predictors of early treatment discontinuation in clinical practice.
Among prevalent or new users of angiotensin-converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARB), angiotensin receptor-neprilysin inhibitors (ARNI), and mineralocorticoid receptor antagonists (MRAs) in the CHAMP-HF (Change the Management of Patients with Heart Failure) registry, we estimated the frequency and independent predictors of treatment discontinuation during follow-up. Among sites with >5 users of a given RAAS inhibitor, we evaluated practice variation in the proportion of patients with treatment discontinuation.
Over median follow-up of 18 months, frequency of drug discontinuation of ACEi/ARB, ARNI, and MRA was 12.7% (444 of 3,509 users), 10.4% (140 of 1,352 users), and 20.4% (435 of 2,129 users), respectively. An additional, 149 (11.0%) of ARNI users were switched to ACEi/ARB and 447 (12.7%) ACEi/ARB users were switched to ARNI during follow-up. Across sites, the median proportion of discontinuation of ACEi/ARB, ARNI, and MRA was 12.5% (25-75 percentiles 6.9-18.9%), 18.8% (25-75 percentiles 12.5-28.6%), and 19.6% (25-75 percentiles 10.7-27.0%), respectively. Chronic kidney disease was the only independent predictor of increased risk of discontinuation of each of the RAAS inhibitor classes (P<0.02 for all). Higher Kansas City Cardiomyopathy Questionnaire overall summary scores independently predicted lower risk of discontinuation of ACEi/ARB and ARNI (both P<0.001), but not MRA. Investigator clinical experience was predictive of lower risks of discontinuation of ACEi/ARB and MRA (P<0.02), but not ARNI. All other independent predictors of discontinuation were unique to individual therapeutic classes.
One in 10 patients discontinue ACEi/ARB or ARNI and 1 in 5 discontinue MRA in routine clinical practice of HFrEF. Unique patient-level and clinician/practice-level factors are associated with premature discontinuation of individual RAAS inhibitors, which may help to guide structured efforts to promote treatment persistence in clinical care.

Copyright © 2021. Published by Elsevier Inc.