Use of acid-suppressive drugs and risk of pneumonia: a systematic review and meta-analysis

Background: Observational studies and randomized controlled trials have yielded inconsistent findings about the association between the use of acid-suppressive drugs and the risk of pneumonia. We performed a systematic review and meta-analysis to summarize this association. Methods: We searched three electronic databases (MEDLIN E [PubMed], Embase and the Cochrane Library) from inception to Aug. 28, 2009. Two evaluators independently extracted data. Because of heterogeneity, we used random-effects meta-analysis to obtain pooled estimates of effect. Results: We identified 31 studies: five case-control studies, three cohort studies and 23 randomized controlled trials. A meta-analysis of the eight observational studies showed that the overall risk of pneumonia was higher among people using proton pump inhibitors (adjusted odds ratio [OR] 1.27, 95% confidence interval [CI] 1.11-1.46, I-2 90.5%) and histamine 2 receptor antagonists (adjusted OR 1.22, 95% CI 1.09-1.36, I-2 0.0%). In the randomized controlled trials, use of histamine 2 receptor antagonists was associated with an elevated risk of hospital-acquired pneumonia (relative risk 1.22, 95% CI 1.01-1.48, I-2 30.6%). Interpretation: Use of a proton pump inhibitor or histamine 2 receptor antagonist may be associated with an increased risk of both community- and hospital-acquired pneumonia. Given these potential adverse effects, clinicians should use caution in prescribing acid-suppressive drugs for patients at risk.