Can Medications be Safely Withdrawn in Patients With Stable Chronic Heart Failure? Systematic Review and Meta-analysis

BackgroundHeart 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 ResultsA 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 Studies in peripartum cardiomyopathy showed that medications could be successfully withdrawn after recovery.ConclusionCurrent evidence discourages any attempt to discontinue RAAS inhibitors or beta-blockers in patients with stable HF, regardless of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.