Risk of Ischaemic Stroke Varies With Antithrombotic Drugs Use in Proton Pump Inhibitor Users: A Self-Controlled Case Series Study

Abstract

Background: The conflicting findings on the association between proton pump inhibitors (PPIs) and ischaemic stroke could be due to residual confounding. Self-controlled case series (SCCS) can be used to avoid time-invariant confounding. Additionally, different baseline risks of stroke should be considered, as some individuals may be prescribed PPIs for gastroprotection from bleeding with antithrombotic drugs. Methods: We identified adult patients with incident ischaemic stroke from 2003 to 2014 in Hong Kong and applied the modified SCCS. The exposure window was pre-defined as Days 1–30, 31–60, 61–90, and 91 to the prescription end, since the PPI prescription. All other periods were referent windows. We estimated incidence rate ratios (IRR) and stratified them further using antithrombotic drugs. Results: A total of 18 170 patients were included. The IRRs for ischaemic stroke were 1.55 (95% CI: 1.00–2.42) during days 61 to 90, 1.51 (95% CI: 1.14–2.00) during days 91 to end, versus the referent window. There was no evidence of an increased risk in other risk windows versus the referent windows. In the stratified analysis, we observed an increased risk in people co-prescribed PPIs with antithrombotic drugs in all risk periods, but no increased risks among those with PPI monotherapy versus the referent window. Conclusion: No evidence of a higher ischaemic stroke after monotherapy of PPI use. The increased risk of ischaemic stroke associated with PPIs could be due to their high baseline risk prescribed with antithrombotic drugs for primary prevention. Clinical monitoring of ischaemic stroke is recommended in these people.