Withdrawal versus continuation of guideline-directed medical therapy in heart failure with improved ejection fraction: a systematic review and meta-analysis.

BACKGROUND

Heart failure with improved ejection fraction (HFimpEF) is characterized by recovery of left ventricular systolic function after treatment for heart failure with reduced ejection fraction. The safety of withdrawing guideline-directed medical therapy (GDMT) after recovery remains uncertain.

OBJECTIVE

To evaluate the effects of GDMT withdrawal versus continuation in patients with recovered or improved left ventricular systolic function.

METHODS

A systematic review was conducted according to PRISMA 2020 guidelines. MEDLINE, Embase, LILACS, and the Cochrane Central Register of Controlled Trials were searched through March 2025. Comparative studies evaluating GDMT withdrawal versus continuation in HFimpEF were included. The primary outcome was relapse of left ventricular systolic dysfunction. Secondary outcomes were heart failure hospitalization, mortality, and quality of life.

RESULTS

Eight studies were included. Relapse of left ventricular dysfunction occurred in up to 58% of patients after therapy withdrawal in recovered dilated cardiomyopathy, whereas most patients with atrial fibrillation-mediated cardiomyopathy maintained preserved ventricular function during short-term follow-up. In a meta-analysis of three prospective studies (n = 133), GDMT withdrawal was associated with a significantly increased risk of relapse compared with continued therapy (OR 15.37, 95% CI 2.75-85.82; I2 = 0%). Observational studies consistently reported higher rates of heart failure hospitalization and adverse cardiovascular outcomes after treatment withdrawal.

CONCLUSIONS

GDMT withdrawal may increase the risk of recurrent ventricular dysfunction and adverse cardiovascular outcomes in HFimpEF. The available evidence supports continuation of therapy in most patients, although further randomized studies are needed to identify patients who may safely discontinue treatment.