Risk of post-stroke pneumonia with proton pump inhibitors, H2 receptor antagonists and mucoprotective agents: A retrospective nationwide cohort study

• Published in: PloS one Vol. 14; no. 5; p. e0216750
• Main Authors: Song, Tae-Jin, Kim, Jinkwon
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 08.05.2019; Public Library of Science (PLoS)
• Subjects: Acids; Age; Aged; Anti-Ulcer Agents - adverse effects; Bactericidal activity; Biology and Life Sciences; Chronic obstructive pulmonary disease; Codes; Cohort analysis; Cohort Studies; Confidence intervals; Demulcents - adverse effects; Dependent variables; Drug development; Drug dosages; Family income; Female; Gastric Acid - metabolism; Gastric juice; Health insurance; Health risks; Histamine H2 Antagonists - adverse effects; Hospitals; Households; Humans; Hypertension; Infections; Inhibitors; Ischemia; Male; Medical diagnosis; Medical imaging; Medicine and Health Sciences; Middle Aged; Misoprostol; Neurology; Pneumonia; Pneumonia - epidemiology; Pneumonia - etiology; Prevention; Proton pump inhibitors; Proton Pump Inhibitors - adverse effects; Protons; Regression analysis; Republic of Korea - epidemiology; Retrospective Studies; Risk; Risk Factors; Social Sciences; Statistical analysis; Stroke; Stroke - complications; Stroke - drug therapy; Time dependence; Ulcers; Republic of Korea
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0216750

Stroke patients are at high risk of developing pneumonia, which is major cause of post-stroke mortality. Proton pump inhibitors and H2 receptor antagonists are anti-ulcer drugs, which may predispose to the development of pneumonia by suppression of the gastric acid with bactericidal activity. Unlike proton pump inhibitors and H2 receptor antagonists, mucoprotective agents have gastroprotective effects with no or less anti-acid property. We aimed to investigate effects of the acid-suppressive medications (proton pump inhibitors and H2 receptor antagonists) and mucoprotective agents on risk for post-stroke pneumonia using the National Health Insurance Service-National Sample Cohort in Korea. This retrospective cohort study included 8,319 patients with acute ischemic stroke. Use of proton pump inhibitors, H2 receptor antagonists, and mucoprotective agents (rebamipide, teprenone, irsogladine, ecabet, polaprezinc, sofalcone, sucralfate, and misoprostol) after stroke were determined based on the prescription records, which were treated as time-dependent variables. Primary outcome was the development of post-stroke pneumonia. During the mean follow-up period of 3.95 years after stroke, 2,035 (24.5%) patients had pneumonia. In the multivariate time-dependent Cox regression analyses (adjusted hazard ratio [95% confidence interval]), there was significantly increased risk for pneumonia with use of proton pump inhibitors (1.56 [1.24-1.96]) and H2 receptor antagonists (1.40 [1.25-1.58]). In contrast to the proton pump inhibitors and H2 receptor antagonists, use of mucoprotective agents did not significantly increase the risk for pneumonia (0.89 [0.78-1.01]). In conclusion, the treatment with proton pump inhibitors and H2 receptor antagonists was associated with increased risk for pneumonia in stroke patients. Clinicians should use caution in prescribing the acid-suppressive medications for the stroke patients at great risk for pneumonia.