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

Abstract

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.

Keywords: Epidemiology; Gastroesophageal Reflux Disease; Meta-Analysis; Proton Pump Inhibition.

Figure 1

Forest plot of the association between the use of proton pump inhibitors (PPIs) and the 6-month cumulative incidence of hospitalisation for community-acquired pneumonia in a restricted cohort of new users of non-steroidal anti-inflammatory drugs (NSAIDs). Analyses were adjusted for age, sex, previous non-hospitalised pneumonia, prescription of  PPIs, histamine-2 receptor antagonists and NSAIDs  in the 7–12 months prior to cohort entry, and high-dimensional propensity score decile. GPRD,  General Practice Research Database.

Figure 2

Forest plot of the association between the use of histamine-2 receptor antagonists and the 6-month cumulative incidence of hospitalisation for community-acquired pneumonia in a restricted cohort of new users of non-steroidal anti-inflammatory drugs (NSAIDs). Analyses were adjusted for age, sex, previous non-hospitalised pneumonia, prescription of proton pump inhibitors, histamine-2 receptor antagonists and NSAIDs in the 7–12 months prior to cohort entry, and high-dimensional propensity score decile. GPRD, General Practice Research Database.