Antiplatelet-Proton Pump Inhibitor Interactions and Arterial Thrombotic Events: A Pharmacovigilance Assessment Using Disproportionality and Interaction Analysis.

Abstract

Aims: The aim of this study is to evaluate the safety profiles of antiplatelet-proton pump inhibitors (PPIs) combinations and assess the clinical implications of their concurrent use in real-world settings through pharmacovigilance data analysis.

Background: The concomitant use of PPIs with antiplatelet therapy remains controversial due to potential drug interactions affecting clinical outcomes. While PPIs are recommended for gastroprotection in patients receiving antiplatelet therapy, concerns persist regarding their impact on antiplatelet efficacy, particularly with dual antiplatelet therapy (DAPT).

Objectives: The objective of this study is to analyze and compare the thrombo-embolic risk profiles of various antiplatelet-PPI combinations using the FDA Adverse Event Reporting System database.

Methods: We conducted a comprehensive analysis of the FDA Adverse Event Reporting System (FAERS) database to evaluate the thrombo-embolic risk associated with antiplatelet-PPI combinations. The reporting odds ratio (ROR) and information component were calculated to detect safety signals. The interaction signal score (INTSS) was used to assess the protective or harmful effects of adding acetylsalicylic acid to clopidogrel-PPI combinations.

Results: Analysis revealed significant safety signals for thrombo-embolic events with clopidogrel-rabeprazole (ROR: 62.67, 95% CI: 38.38-102.32) and clopidogrel-omeprazole (ROR: 6.87, 95% CI: 4.89-9.66) combinations. DAPT-PPI combinations showed comparable safety profiles to monotherapy-PPI combinations. The INTSS analysis suggested a potential protective effect of acetylsalicylic acid when added to clopidogrel-PPI combinations. Genderspecific analysis revealed female predominance in monotherapy complications and male predominance in combination therapy events. Clinical outcomes, including mortality and hospitalization rates, were comparable between groups.

Conclusion: This pharmacovigilance analysis suggests that while DAPT-PPI combinations demonstrate acceptable safety profiles, careful consideration should be given to PPI selection, particularly given the unexpected safety signals with rabeprazole and confirmed risks with omeprazole. The addition of acetylsalicylic acid to clopidogrel-PPI combinations may offer protective effects against thrombo-embolic events. These findings support individualized riskbenefit assessment in selecting antiplatelet-PPI combinations while ensuring adequate gastroprotection for high-risk patients.