Tolerability of angiotensin-receptor blockers in patients with intolerance to angiotensin-converting enzyme inhibitors: a systematic review and meta-analysis

Am J Cardiovasc Drugs. 2012 Aug 1;12(4):263-77. doi: 10.1007/BF03261835.


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.

Data sources: The electronic databases PubMed, MEDLINE/EMBASE via Dialog, CENTRAL, and ISI Web of Knowledge were searched.

Study selection: Randomized controlled trials (RCTs) evaluating ARBs in patients with intolerance to ACE inhibitors were selected.

Data synthesis: 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.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Angioedema / chemically induced
  • Angiotensin Receptor Antagonists / adverse effects*
  • Angiotensin-Converting Enzyme Inhibitors / adverse effects*
  • Cough / chemically induced
  • Humans
  • Hyperkalemia / chemically induced
  • Hypotension / chemically induced
  • Hypotension / drug therapy*
  • Kidney Diseases / chemically induced


  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors