Simplification of Treatment by Withdrawal of Medications in Stable Heart Failure With Improved Left Ventricular Ejection Fraction

Heart failure (HF) is a major global health problem associated with high rates of hospitalization, mortality, and healthcare costs. Contemporary guideline-directed medical therapy has substantially improved outcomes in patients with heart failure with reduced ejection fraction (HFrEF). Standard pharmacological management includes four major therapeutic pillars: beta-blockers, inhibitors of the renin-angiotensin system (ACE inhibitors, ARBs, or ARNI), mineralocorticoid receptor antagonists (MRAs), and sodium-glucose cotransporter-2 (SGLT2) inhibitors. These therapies improve survival and reduce hospitalizations.

A subset of patients with HFrEF experiences significant improvement in cardiac function after treatment and is now classified as having heart failure with improved ejection fraction (HFimpEF). These patients typically demonstrate recovery of left ventricular ejection fraction from previously reduced values to ≥40%. However, recovery of ejection fraction does not necessarily represent complete reversal of the underlying disease process, and structural or molecular abnormalities may persist. Current clinical guidelines generally recommend continuation of guideline-directed medical therapy even after improvement in ejection fraction due to concerns about relapse.

Despite the benefits of these therapies, patients with heart failure frequently require multiple medications to manage both their cardiac condition and associated comorbidities. Polypharmacy can increase the risk of adverse drug reactions, medication non-adherence, drug interactions, and treatment complexity. Simplification of pharmacological regimens may therefore represent an important strategy to improve adherence and reduce treatment burden in selected patients.

Previous studies investigating withdrawal of heart failure therapies have shown mixed results. In some populations, withdrawal of key disease-modifying medications resulted in relapse of cardiac dysfunction or worsening clinical status. However, there is limited evidence regarding selective withdrawal of specific medication classes in carefully selected patients who have achieved clinical stability and significant improvement in cardiac function.

Mineralocorticoid receptor antagonists, such as spironolactone, play an important role in the treatment of HFrEF by blocking the effects of aldosterone, thereby reducing myocardial fibrosis, neurohormonal activation, and ventricular remodeling. Although their benefits in patients with reduced ejection fraction are well established, the necessity of maintaining this therapy indefinitely in patients with stable HFimpEF remains uncertain.