title: Tolerability of angiotensin-receptor blockers in patients with intolerance to angiotensin-converting enzyme inhibitors: a systematic review and meta-analysis.
abstract: BACKGROUND
  Between 5% and 20% of patients treated with angiotensin-converting enzyme inhibitors (ACE inhibitors) develop intolerance. Angiotensin II type 1 receptor antagonists (angiotensin receptor blockers [ARBs]) can be used as an alternative treatment.
  
  
  OBJECTIVE
  In this study we aimed to evaluate the tolerability of ARBs in patients with intolerance to ACE inhibitors.
  
  
  METHODS
  The electronic databases PubMed, MEDLINE/EMBASE via Dialog, CENTRAL, and ISI Web of Knowledge were searched.
  
  
  METHODS
  Randomized controlled trials (RCTs) evaluating ARBs in patients with intolerance to ACE inhibitors were selected.
  
  
  RESULTS
  Risk ratio (RR) and 95% confidence intervals (CIs) were estimated assuming the random effects method. We found 11 RCTs comparing ARBs with ACE inhibitors, diuretics, or placebo, and one RCT comparing high-dose versus low-dose ARB.
  
  
  RESULTS
  ARBs had fewer cough events versus ACE inhibitors (RR 0.37; 95% CI 0.28, 0.48). ARBs had drug discontinuation (RR 0.99; 95% CI 0.84, 1.17) and cough risk (RR 1.01; 95% CI 0.74, 1.39) rates similar to placebo. Angioedema risk with ARBs was also similar to placebo (RR 1.62; 95% CI 0.17, 15.79). Compared with placebo, hypotension (RR 2.63; 95% CI 1.77, 3.92), renal dysfunction (RR 2.07; 95% CI 1.45, 2.95) and hyperkalemia (RR 3.37; 95% CI 1.60, 7.11) were more frequent with ARBs.
  
  
  CONCLUSIONS
  ACE inhibitor rechallenge should be discouraged in patients with previous intolerance to ACE inhibitors due to a higher risk of cough. ARBs had cough and angioedema incidences similar to placebo. Despite a significantly higher incidence of hypotension, renal dysfunction and hyperkalemia, discontinuation of ARBs was similar to placebo.
authors.affiliation: Clinical Pharmacology and Therapeutics Laboratory, Faculty of Medicine, Lisbon, Portugal. dgcaldeira@hotmail.com
authors.forename: Daniel
authors.initials: D
authors.lastname: Caldeira
authors.forename: Cláudio
authors.initials: C
authors.lastname: David
authors.forename: Cristina
authors.initials: C
authors.lastname: Sampaio
mesh_terms: D000799:Angioedema / Q000139:chemically induced; D057911:Angiotensin Receptor Antagonists / Q000009:adverse effects*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects*; D003371:Cough / Q000139:chemically induced; D006801:Humans; D006947:Hyperkalemia / Q000139:chemically induced; D007022:Hypotension / Q000139:chemically induced / Q000188:drug therapy*; D007674:Kidney Diseases / Q000139:chemically induced
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors