Histamine H2-Blocker and Proton Pump Inhibitor Use and the Risk of Pneumonia in Acute Stroke: A Retrospective Analysis on Susceptible Patients

BACKGROUND: Although histamine H2-blockers (H2B) and proton pump inhibitors (PPI) are used commonly to prevent gastrointestinal bleeding in acute stroke, they are implicated in the increased risk of pneumonia in other disease populations. In acute stroke, the presence of distinctive risk factors of pneumonia, including dysphagia and impaired consciousness, makes inclusive analysis vulnerable to confounding. Our aim was to assess whether acid-suppressive drugs increase pneumonia in acute stroke in a population controlled for confounding. METHODS: We analyzed acute stroke patients admitted to a tertiary care hospital. To minimize confounding, we only included subjects who could not feed orally during 14 days of hospitalization. Exposure was defined as H2B or PPI, given in days; the outcome was development of pneumonia within this period. The incidence was calculated from the total number of pneumonias divided by the sum of person-days at risk. We additionally performed multivariate Poisson regression and propensity score analyses, although the restriction largely eliminated the need for multivariate adjustment. RESULTS: A total of 132 pneumonias occurred in 3582 person-days. The incidence was 3.69%/person-day (95% confidence interval (CI); 3.03–4.37%/day). All subjects had dysphagia. Stroke severity and consciousness disturbances were well-balanced between the groups exposed to H2B, PPI, or none. The relative risk (RR) compared with the unexposed was 1.22 in H2B (95%CI; 0.83–1.81) and 2.07 in PPI (95% CI; 1.13–3.62). The RR of PPI compared with H2B was 1.69 (95%CI; 0.95–2.89). In multivariate regression analysis, the RRs of H2B and PPI were 1.24 (95% CI; 0.85–1.81) and 2.00 (95% CI; 1.12–3.57), respectively; in propensity score analyses they were 1.17 (95% CI; 0.89–1.54) and 2.13 (95% CI; 1.60–2.84). CONCLUSIONS: The results of this study suggested that prophylactic acid-suppressive therapy with PPI may have to be avoided in acute stroke patients susceptible to pneumonia.