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

Abstract

Background Clopidogrel is an irreversible antagonist of P2Y12 receptors (P2Y12Rs) used as an antiplatelet drug to reduce risk of thrombosis. P2Y12Rs are expressed in gastrointestinal (GI) tract where they might regulate GI function. Aim To evaluate if blockade of P2Y12Rs 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 P2Y12R 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). P2Y12R immunoreactivity was abundant in human ENS; glial-to-neuron ratio of P2Y12Rs expressed in Females ≫ Males. Conclusions Irreversible blockade of P2Y12R 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 P2Y12Rs in IBS.

Comparative Risk of Hospitalized Bleeding of P2Y12 Inhibitors for Secondary Prophylaxis in Acute Coronary Syndrome After Percutaneous Coronary Intervention

“…Both drugs are irreversibly bound to P2Y12 receptors to produce an antiplatelet effect, whereas ticagrelor, a reversible inhibitor, does not require bioactivation 17 . In a previous study, irreversible inhibition of P2Y12 receptors was hypothesized to be responsible for the overstimulation of gut reflexes 18 . These pharmacokinetic differences combined with angiogenic factors inhibition 9,10 may produce a distinct GI bleeding risk based on the P2Y12 inhibitor used.…”

“… 17 In a previous study, irreversible inhibition of P2Y12 receptors was hypothesized to be responsible for the overstimulation of gut reflexes. 18 These pharmacokinetic differences combined with angiogenic factors inhibition 9 , 10 may produce a distinct GI bleeding risk based on the P2Y12 inhibitor used.…”

<p>Increased Risk of Clopidogrel-Induced Gastric Mucosal Erosion in Elderly Chinese Men Harboring the <em>ABCB1 3435T</em> Allele</p>

“…Clopidogrel can be used alone by patients who require secondary stroke prevention or have and intolerance of aspirin and by children. 5,14,15 It mainly works by blocking the platelet P2Y12 receptor to exert antiplatelet effects. Anderson et al found that the antiplatelet effect of clopidogrel activated before standard accepted biotransformation pathways.…”