Proton pump inhibitors and the risk of hospitalisation for community-acquired pneumonia: replicated cohort studies with meta-analysis

Objective Previous observational studies suggest that the use of proton pump inhibitors (PPIs) may increase the risk of hospitalisation for community-acquired pneumonia (HCAP). However, the potential presence of confounding and protopathic biases limits the conclusions that can be drawn from these studies. Our objective was, therefore, to examine the risk of HCAP with PPIs prescribed prophylactically in new users of non-steroidal anti-inflammatory drugs (NSAIDs). Design We formed eight restricted cohorts of new users of NSAIDs, aged >= 40 years, using a common protocol in eight databases (Alberta, Saskatchewan, Manitoba, Ontario, Quebec, Nova Scotia, US MarketScan and the UK's General Practice Research Database (GPRD)). This specific patient population was studied to minimise bias due to unmeasured confounders. High-dimensional propensity scores were used to estimate site-specific adjusted ORs (aORs) for HCAP at 6 months in PPI patients compared with unexposed patients. Fixed-effects meta-analytic models were used to estimate overall effects across databases. Results Of the 4 238 504 new users of NSAIDs, 2.3% also started a PPI. The cumulative 6-month incidence of HCAP was 0.17% among patients prescribed PPIs and 0.12% in unexposed patients. After adjustment, PPIs were not associated with an increased risk of HCAP (aOR=1.05; 95% CI 0.89 to 1.25). Histamine-2 receptor antagonists yielded similar results (aOR=0.95, 95% CI 0.75 to 1.21). Conclusions Our study does not support the proposition of a pharmacological effect of gastric acid suppressors on the risk of HCAP.