Clopidogrel IBS Patients Have Higher Incidence of Gastrointestinal Symptoms Influenced by Age and Gender

Background Clopidogrel is an irreversible antagonist of P2Y 12 receptors (P2Y 12 Rs) used as an antiplatelet drug to reduce risk of thrombosis. P2Y 12 Rs are expressed in gastrointestinal (GI) tract where they might regulate GI function. Aim To evaluate if blockade of P2Y 12 Rs by clopidogrel is associated with higher incidence of GI symptoms in patients with irritable bowel syndrome (IBS). Methods A retrospective analysis of our institutional database was conducted for a 13-year period. IBS patients were identified, and their demographics, GI symptoms and clopidogrel therapy were collected. Logistic regression models were used to characterize symptoms in clopidogrel versus no-clopidogrel IBS-groups, adjusting for Age and Sex differences. An additional study characterized the P2Y 12 R distribution in human gut. Results The search identified 7217 IBS patients (6761 no-clopidogrel/456 clopidogrel). There were a higher proportion of patients with GI symptoms on clopidogrel (68%) compared to controls (60%, p = 0.0011) that were Females (70 vs. 60%, p = 0.0003) not Males (61 vs. 60%; p = 0.8312). In Females, clopidogrel was associated with higher incidence of GI symptoms (Age adjusted; p < 0.0001) for pain, constipation, gastroparesis ( p ≤ 0.0001) and psychogenic pain ( p = 0.0006). Age or Sex (adjusted models) influenced one or more GI symptoms (i.e., pain, p < 0.0001; constipation, p < 0.0001/ p = 0.008; diarrhea, flatulence, p = 0.01). P2Y 12 R immunoreactivity was abundant in human ENS; glial-to-neuron ratio of P2Y 12 Rs expressed in Females ≫ Males. Conclusions Irreversible blockade of P2Y 12 R by clopidogrel is associated with higher incidence of GI symptoms in Female IBS patients, although Age or Sex alone contributes to symptomatology. Prospective studies can determine clinical implications of P2Y 12 Rs in IBS.