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

A Systematic Review and Meta-Analysis

Caldeira, Daniel
David, Cláudio
Sampaio, Cristina

¹ Clinical Pharmacology and Therapeutics Laboratory, Faculty of Medicine, Lisbon, Portugal
² Department of Cardiology, Santa Maria University Hospital, Lisbon, Portugal
³ Institute of Molecular Medicine, Lisbon, Portugal

Correspondence: Dr Daniel Caldeira, Laboratório de Farmacologia Clínica e Terapêutica, Faculdade de Medicina da Universidade de Lisboa, Av. Prof. Egas Moniz, Lisboa, 1649-028, Portugal.

E-mail: [email protected]

American Journal of Cardiovascular Drugs 12(4):p 263-277, August 1, 2012. | DOI: 10.2165/11599990-000000000-00000

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.