The necessity of lifelong treatment and polypharmacy in chronic heart failure (HF) patients with improved myocardial function remains debated. This systematic review aims to synthesize current literature regarding this issue.
A systematic literature search was performed in MEDLINE, Embase, and Cochrane Central Register of Controlled Trials from the inception to 18 October 2024. Seven studies (n = 552) reporting minimization or withdrawal of pharmacotherapy in chronic HF patients with improved ejection fraction or stable New York Heart Association status were included. Findings were heterogeneous due to variations in study design and protocols. Loop diuretic withdrawal was favoured by one non-randomized study (n = 26) and one randomized controlled trial (RCT) (n = 188). Minimization of angiotensin receptor-neprilysin inhibitors (n = 77) or withdrawal of mineralocorticoid receptor antagonists (MRA) (n = 70) was not favourable. Carvedilol monotherapy was favoured by one small-sample RCT (n = 60). One RCT (n = 51) reported a high overall relapse rate (65%) following multiple drug withdrawal in recovered patients with dilated cardiomyopathy. Another RCT (n = 80) found a low occurrence of cardiac dimensional deterioration (7.5%) following multiple drug withdrawal in post-cardiac resynchronization therapy patients with normalized ejection fraction. However, 28% required drug re-initiation due to cardiac comorbidities.
The existing evidence on minimizing or withdrawing oral pharmacotherapy in chronic HF patients with improved myocardial function remains very limited and heterogeneous, supporting only loop diuretic withdrawal and possibly carvedilol monotherapy, but not the minimization or withdrawal of renin-angiotensin system inhibitors, MRA, or the combination of HF medications. Large RCTs are needed to determine the appropriate treatment strategy.

© 2025 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.