Abstract

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

Soghomonyan S1, Abdel-Rasoul M2, Zuleta-Alarcon A1, Grants I1, Davila V1, Yu J1, Zhang C3, Whitaker EE1,4, Bergese SD1, Stoicea N1, Arsenescu R3,5, Christofi FL6. Dig Dis Sci. 2017 Aug 24. doi: 10.1007/s10620-017-4707-7. [Epub ahead of print]
 
     
Author information

1 Department of Anesthesiology, The Wexner Medical Center, The Ohio State University, 420 West 12th Ave, Room 226, Columbus, OH, 43210, USA. 2 Department of Biomedical Informatics, Center for Biostatistics, The Ohio State University, 1800 Cannon Drive, Room 320, Columbus, OH, 43210, USA. 3 Department of Internal Medicine, Wexner Medical Center, The Ohio State University, 395 West 12th Ave, Suite 200, Columbus, OH, 43210, USA. 4 Department of Anesthesiology and Pain Medicine, Nationwide Children's Hospital, 700 Children's Drive, Columbus, OH, 43205, USA. 5 Atlantic Inflammatory Bowel Disease Center of Excellence, Atlantic Digestive Health Institute, 435 South Street, Suite 205, Morristown, NJ, 07960, USA. 6 Department of Anesthesiology, The Wexner Medical Center, The Ohio State University, 420 West 12th Ave, Room 226, Columbus, OH, 43210, USA. Fedias.Christofi@osumc.edu.

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.

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