Effect of proton-pump inhibitors on the risk of lower gastrointestinal bleeding associated with NSAIDs, aspirin, clopidogrel, and warfarin

Abstract

We investigated the effects of proton-pump inhibitors (PPIs) on lower gastrointestinal bleeding (LGIB) and of their interactions with nonsteroidal anti-inflammatory drugs (NSAIDs), low-dose aspirin, clopidogrel, and warfarin on LGIB risk. We prospectively studied 355 patients emergently hospitalized for LGIB and 8,221 nonbleeding patients. All patients underwent colonoscopy. Smoking, alcohol drinking, drug exposure, and the Charlson comorbidity index score were assessed before colonoscopy. Adjusted odds ratios (AOR) of LGIB were estimated. LGIB was significantly associated with older age, higher comorbidity index, and NSAID, aspirin, clopidogrel, or warfarin use. PPI use was significantly associated with older age, male sex, being a current alcohol drinker, higher comorbidity index, and NSAID, aspirin, clopidogrel, warfarin, acetaminophen, or corticosteroid use. Multivariate analysis adjusted by the confounding factors revealed LGIB was not significantly associated with PPI use (AOR 0.87; 95 % confidence interval 0.68-1.13; p = 0.311), or specifically with omeprazole (AOR 1.18; p = 0.408), esomeprazole (AOR 0.76; p = 0.432), lansoprazole (AOR 0.93; p = 0.669), or rabeprazole (AOR 0.63; p = 0.140). In the interaction model, no significant interactions were observed between PPIs and NSAIDs (AOR 1.40; p = 0.293), aspirin (AOR 1.09; p = 0.767), clopidogrel (AOR 0.99, p = 0.985), or warfarin (AOR 1.52; p = 0.398). This large case-control study demonstrated that PPI use did not lead to an increased risk of LGIB, regardless of the type of PPI used. Further, LGIB risk was not affected by PPI use, irrespective of concomitant therapy with NSAIDs, low-dose aspirin, clopidogrel, or warfarin.