Risk of pneumonia associated with use of angiotensin converting enzyme inhibitors and angiotensin receptor blockers : systematic review and meta-analysis

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/bync/2.0/ and http://creativecommons.org/licenses/by-nc/2.0/legalcode.OBJECTIVE: To systematically review longitudinal studies evaluating use of angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) and risk of pneumonia. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Medline through PubMed, Web of Science with conference proceedings (inception to June 2011), and US Food and Drug Administration website (June 2011). Systematic reviews and references of retrieved articles were also searched. STUDY SELECTION: Two reviewers independently selected randomised controlled trials and cohort and case-control studies evaluating the use of ACE inhibitors or ARBs and risk of pneumonia and retrieved characteristics of the studies and data estimates. DATA SYNTHESIS: The primary outcome was incidence of pneumonia and the secondary outcome was pneumonia related mortality. Subgroup analyses were carried according to baseline morbidities (stroke, heart failure, and chronic kidney disease) and patients' characteristics (Asian and non-Asian). Pooled estimates of odds ratios and 95% confidence intervals were derived by random effects meta-analysis. Adjusted frequentist indirect comparisons between ACE inhibitors and ARBs were estimated and combined with direct evidence whenever available. Heterogeneity was assessed using the I(2) test. RESULTS: 37 eligible studies were included. ACE inhibitors were associated with a significantly reduced risk of pneumonia compared with control treatment (19 studies: odds ratio 0.66, 95% confidence interval 0.55 to 0.80; I(2) = 79%) and ARBs (combined direct and indirect odds ratio estimate 0.69, 0.56 to 0.85). In patients with stroke, the risk of pneumonia was also lower in those treated with ACE inhibitors compared with control treatment (odds ratio 0.46, 0.34 to 0.62) and ARBs (0.42, 0.22 to 0.80). ACE inhibitors were associated with a significantly reduced risk of pneumonia among Asian patients (0.43, 0.34 to 0.54) compared with non-Asian patients (0.82, 0.67 to 1.00; P