Background: Heart failure (HF) therapy involves use of multiple medications. There is little guidance on the safety and impact on clinical outcomes of stopping HF medications.
Methods And Results: A comprehensive systematic search for studies of drug therapy withdrawal in HF was performed. Meta-analysis of the risk ratio (RR) was performed with the use of the Mantel-Haenszel random effects model for all-cause mortality and cardiovascular outcomes. Twenty-six studies met the inclusion criteria. Studies on withdrawal of renin-angiotensin-aldosterone system (RAAS) inhibitors and beta-blockers in HF are scarce and small, yet show relatively convincingly that such withdrawals have untoward effects on cardiac structure, symptoms, and major outcomes. Meta-analysis of 7 studies of digoxin withdrawal (2,987 participants) without background beta-blocker showed increased HF hospitalizations (RR 1.30, 95% confidence interval [CI] 1.16-1.46; P < .0001), but no impact on all-cause mortality (RR 1.00, 95% CI 0.90-1.12; P = .06) nor reduction in all-cause hospitalization (RR 1.03, 95% CI 0.98-1.09; P = .27). Diuretic withdrawal trials demonstrated an ongoing need for these agents in chronic HF. Studies in peripartum cardiomyopathy showed that medications could be successfully withdrawn after recovery.
Conclusion: Current evidence discourages any attempt to discontinue RAAS inhibitors or beta-blockers in patients with stable HF, regardless of clinical and/or echocardiographic status. Formal withdrawal trials of other classes are needed.
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