title: Can medications be safely withdrawn in patients with stable chronic heart failure? systematic review and meta-analysis.
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.
  
  
  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 Studies in peripartum cardiomyopathy showed that medications could be successfully withdrawn after recovery.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Centre of Cardiovascular Research and Education in Therapeutics, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia; Department of Clinical Pharmacology, Alfred Health, Melbourne, Australia. Electronic address: ingrid.hopper@monash.edu.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Hopper
authors.affiliation: Centre of Cardiovascular Research and Education in Therapeutics, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia.
authors.forename: Rohit
authors.initials: R
authors.lastname: Samuel
authors.affiliation: St Vincent's Hospital and Victor Chang Cardiac Research Institute, Sydney, Australia.
authors.forename: Christopher
authors.initials: C
authors.lastname: Hayward
authors.affiliation: Centre of Cardiovascular Research and Education in Therapeutics, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Tonkin
authors.affiliation: Centre of Cardiovascular Research and Education in Therapeutics, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia; Department of Clinical Pharmacology, Alfred Health, Melbourne, Australia.
authors.forename: Henry
authors.initials: H
authors.lastname: Krum
mesh_terms: D002317:Cardiovascular Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002908:Chronic Disease; D006333:Heart Failure / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology*; D006801:Humans; D016032:Randomized Controlled Trials as Topic / Q000379:methods; D013375:Substance Withdrawal Syndrome / Q000175:diagnosis* / Q000453:epidemiology*
chemical_list: D002317:Cardiovascular Agents
keywords: Medication discontinuation; digoxin; peripartum cardiomyopathy; polypharmacy