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

Suren Soghomonyan, Mahmoud Abdel-Rasoul, Alix Zuleta-Alarcon, Iveta Grants, Victor Davila, Jeffrey Yu, Cheng Zhang, Emmett E. Whitaker, Sergio D. Bergese, Nicoleta Stoicea, Razvan Arsenescu, Fievos L. Christofi

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)2728-2743
Number of pages16
JournalDigestive Diseases and Sciences
Volume62
Issue number10
DOIs
StatePublished - Oct 1 2017

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clopidogrel
Irritable Bowel Syndrome
Incidence
Constipation
Pain
Purinergic P2Y Receptor Antagonists
Logistic Models
Gastroparesis
Flatulence

All Science Journal Classification (ASJC) codes

  • Physiology
  • Gastroenterology

Cite this

Soghomonyan, S., Abdel-Rasoul, M., Zuleta-Alarcon, A., Grants, I., Davila, V., Yu, J., ... Christofi, F. L. (2017). Clopidogrel IBS Patients Have Higher Incidence of Gastrointestinal Symptoms Influenced by Age and Gender. Digestive Diseases and Sciences, 62(10), 2728-2743. https://doi.org/10.1007/s10620-017-4707-7
Soghomonyan, Suren ; Abdel-Rasoul, Mahmoud ; Zuleta-Alarcon, Alix ; Grants, Iveta ; Davila, Victor ; Yu, Jeffrey ; Zhang, Cheng ; Whitaker, Emmett E. ; Bergese, Sergio D. ; Stoicea, Nicoleta ; Arsenescu, Razvan ; Christofi, Fievos L. / Clopidogrel IBS Patients Have Higher Incidence of Gastrointestinal Symptoms Influenced by Age and Gender. In: Digestive Diseases and Sciences. 2017 ; Vol. 62, No. 10. pp. 2728-2743.
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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.",
author = "Suren Soghomonyan and Mahmoud Abdel-Rasoul and Alix Zuleta-Alarcon and Iveta Grants and Victor Davila and Jeffrey Yu and Cheng Zhang and Whitaker, {Emmett E.} and Bergese, {Sergio D.} and Nicoleta Stoicea and Razvan Arsenescu and Christofi, {Fievos L.}",
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Soghomonyan, S, Abdel-Rasoul, M, Zuleta-Alarcon, A, Grants, I, Davila, V, Yu, J, Zhang, C, Whitaker, EE, Bergese, SD, Stoicea, N, Arsenescu, R & Christofi, FL 2017, 'Clopidogrel IBS Patients Have Higher Incidence of Gastrointestinal Symptoms Influenced by Age and Gender', Digestive Diseases and Sciences, vol. 62, no. 10, pp. 2728-2743. https://doi.org/10.1007/s10620-017-4707-7

Clopidogrel IBS Patients Have Higher Incidence of Gastrointestinal Symptoms Influenced by Age and Gender. / Soghomonyan, Suren; Abdel-Rasoul, Mahmoud; Zuleta-Alarcon, Alix; Grants, Iveta; Davila, Victor; Yu, Jeffrey; Zhang, Cheng; Whitaker, Emmett E.; Bergese, Sergio D.; Stoicea, Nicoleta; Arsenescu, Razvan; Christofi, Fievos L.

In: Digestive Diseases and Sciences, Vol. 62, No. 10, 01.10.2017, p. 2728-2743.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Clopidogrel IBS Patients Have Higher Incidence of Gastrointestinal Symptoms Influenced by Age and Gender

AU - Soghomonyan, Suren

AU - Abdel-Rasoul, Mahmoud

AU - Zuleta-Alarcon, Alix

AU - Grants, Iveta

AU - Davila, Victor

AU - Yu, Jeffrey

AU - Zhang, Cheng

AU - Whitaker, Emmett E.

AU - Bergese, Sergio D.

AU - Stoicea, Nicoleta

AU - Arsenescu, Razvan

AU - Christofi, Fievos L.

PY - 2017/10/1

Y1 - 2017/10/1

N2 - 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.

AB - 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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