425 Is the Use of Proton Pump Inhibitors Associated With Increased Risk of Ischemic Stroke: A Systematic Review and Meta-Analysis

Abstract

INTRODUCTION: The use of proton-pump inhibitors (PPIs) has been associated with various adverse effects including increased risk of major adverse cardiovascular events, community acquired clostridium difficile infection, chronic kidney disease and dementia. Some studies over the past decade have suggested an association between PPIs use and ischemic stroke. METHODS: We pooled the data after comprehensive literature search from the PubMed, Embase, Cochrane Library and Scopus databases using ‘proton pump inhibitors’ AND ‘stroke’ as the keywords. RevMan was used for the entry and analysis of data. A random effects model was created given the significant heterogeneity of the included studies and a funnel plot was made to assess the publication bias. Our primary objective was to study whether all-comers patients on PPIs are at an increased risk of stroke. Sub-group analysis was also done to investigate the association between patients on dual anti-platelet therapy [DAPT] (aspirin and clopidogrel) with or without PPIs and stroke. RESULTS: After searching 774 titles, 25 titles were selected to be included in the systematic review and 15 articles for the meta-analysis. Our pooled analysis of 155,406 patients (46,652 patients on PPI and 101,892 patients without PPI found a positive association between the use of PPI and stroke (odds ratio = 1.28, 95% confidence interval = 1.12, 1.48, P = 0.001) [Figure 1]. Given the significant heterogeneity of the studies (I2= 60%) a sub-group analysis was done which also suggested an increased risk of stroke associated with PPI use among patients on dual antiplatelet therapy (OR: 1.43, 95% CI: 1.26, 1.66, p< 0.001, I2= 11%) [Figure 2]. Analysis of the included randomized controlled trials revealed an OR: 1.47, 95% CI: 0.66, 3.25 but the results were not statistically significant (p< 0.81) [Figure 3]. CONCLUSION: In a pooled analysis of over 155,000 patients we found a positive association between the use of PPIs and stroke. Our results are limited by significant heterogeneity and retrospective study design of the observational studies. Rigorous clinical trials are needed to establish the safety of PPIs in relation to stroke, especially among patients on DAPT. Until definitive data emerges, patients on DAPT are probably best served by being off PPIs or being on alternative acid suppression regimen, unless there is a compelling indication for PPI use.