Can medications be safely withdrawn in patients with stable chronic heart failure? systematic review and meta-analysis

J Card Fail. 2014 Jul;20(7):522-32. doi: 10.1016/j.cardfail.2014.04.013. Epub 2014 Apr 18.

Abstract

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 Studies in peripartum cardiomyopathy showed that medications could be successfully withdrawn after recovery.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.

Keywords: Medication discontinuation; digoxin; peripartum cardiomyopathy; polypharmacy.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Cardiovascular Agents / administration & dosage*
  • Cardiovascular Agents / adverse effects
  • Chronic Disease
  • Heart Failure / diagnosis
  • Heart Failure / drug therapy*
  • Heart Failure / epidemiology*
  • Humans
  • Randomized Controlled Trials as Topic / methods
  • Substance Withdrawal Syndrome / diagnosis*
  • Substance Withdrawal Syndrome / epidemiology*

Substances

  • Cardiovascular Agents