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

Abstract

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 (MEDLINE [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.

Figure 1:

Selection of observational (case–control and cohort) studies (A) and randomized controlled trials (B) evaluating the risk of pneumonia in association with use of acid-suppressive drugs. *Includes nested case–control studies. H₂RA = histamine₂ receptor antagonist, PPI = proton pump inhibitor, RCT = randomized controlled trial.

Figure 2:

Meta-analyses of observational studies evaluating the risk of pneumonia among patients receiving acid-suppressive drugs, based on random-effects model. Adjusted odds ratios (ORs) greater than 1 indicate increased risk of pneumonia. CI = confidence interval, I² = heterogeneity, n = number of events, N = number of patients, NR = not reported.

Figure 3:

Meta-analysis of randomized controlled trials evaluating the risk of hospital-acquired pneumonia among patients using histamine₂ receptor antagonists, based on random-effects model. Relative risk (RR) values greater than 1 indicate increased risk of pneumonia. CI = confidence interval, I² = heterogeneity, n = number of events, N = number of patients.