American Journal of Cardiovascular Drugs

, Volume 12, Issue 4, pp 263–277

Tolerability of Angiotensin-Receptor Blockers in Patients with Intolerance to Angiotensin-Converting Enzyme Inhibitors

A Systematic Review and Meta-Analysis
  • Daniel Caldeira
  • Cláudio David
  • Cristina Sampaio
Systematic Review

DOI: 10.1007/BF03261835

Cite this article as:
Caldeira, D., David, C. & Sampaio, C. Am J Cardiovasc Drugs (2012) 12: 263. doi:10.1007/BF03261835



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.


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.


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.


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.

Copyright information

© Springer International Publishing AG 2012

Authors and Affiliations

  • Daniel Caldeira
    • 1
  • Cláudio David
    • 1
    • 2
  • Cristina Sampaio
    • 1
    • 3
  1. 1.Clinical Pharmacology and Therapeutics Laboratory, Faculty of MedicineLisbonPortugal
  2. 2.Department of CardiologySanta Maria University HospitalLisbonPortugal
  3. 3.Institute of Molecular MedicineLisbonPortugal