Skip to main content
Erschienen in: Digestive Diseases and Sciences 10/2017

24.08.2017 | Original Article

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

verfasst von: 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

Erschienen in: Digestive Diseases and Sciences | Ausgabe 10/2017

Einloggen, um Zugang zu erhalten

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.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
2.
Zurück zum Zitat Berger JS. Aspirin, clopidogrel, and ticagrelor in acute coronary syndromes. Am J Cardiol. 2013;112:737–745.CrossRefPubMed Berger JS. Aspirin, clopidogrel, and ticagrelor in acute coronary syndromes. Am J Cardiol. 2013;112:737–745.CrossRefPubMed
3.
Zurück zum Zitat Fork FT, Lafolie P, Toth E, Lindgarde F. Gastroduodenal tolerance of 75 mg clopidogrel versus 325 mg aspirin in healthy volunteers. A gastroscopic study. Scand J Gastroenterol. 2000;35:464–469.CrossRefPubMed Fork FT, Lafolie P, Toth E, Lindgarde F. Gastroduodenal tolerance of 75 mg clopidogrel versus 325 mg aspirin in healthy volunteers. A gastroscopic study. Scand J Gastroenterol. 2000;35:464–469.CrossRefPubMed
4.
6.
Zurück zum Zitat Fujikawa T, Tanaka A, Abe T, et al. Does antiplatelet therapy affect outcomes of patients receiving abdominal laparoscopic surgery? Lessons from more than 1,000 laparoscopic operations in a single tertiary referral hospital. J Am Coll Surg. 2013;217:1044–1053.CrossRefPubMed Fujikawa T, Tanaka A, Abe T, et al. Does antiplatelet therapy affect outcomes of patients receiving abdominal laparoscopic surgery? Lessons from more than 1,000 laparoscopic operations in a single tertiary referral hospital. J Am Coll Surg. 2013;217:1044–1053.CrossRefPubMed
7.
Zurück zum Zitat Gentilomo C, Huang YS, Raffini L. Significant increase in clopidogrel use across U.S. children’s hospitals. Pediatr Cardiol. 2011;32:167–175.CrossRefPubMed Gentilomo C, Huang YS, Raffini L. Significant increase in clopidogrel use across U.S. children’s hospitals. Pediatr Cardiol. 2011;32:167–175.CrossRefPubMed
8.
Zurück zum Zitat Shiotani A, Honda K, Murao T, et al. Combination of low-dose aspirin and thienopyridine exacerbates small bowel injury. Scand J Gastroenterol. 2011;46:281–286.CrossRefPubMed Shiotani A, Honda K, Murao T, et al. Combination of low-dose aspirin and thienopyridine exacerbates small bowel injury. Scand J Gastroenterol. 2011;46:281–286.CrossRefPubMed
9.
Zurück zum Zitat Rouine-Rapp K, McDermott MW. Perioperative management of a neurosurgical patient with a meningioma and recent coronary artery stent. J Clin Anesth. 2013;25:228–231.CrossRefPubMed Rouine-Rapp K, McDermott MW. Perioperative management of a neurosurgical patient with a meningioma and recent coronary artery stent. J Clin Anesth. 2013;25:228–231.CrossRefPubMed
10.
Zurück zum Zitat Dimitrova G, Tulman DB, Bergese SD. Perioperative management of antiplatelet therapy in patients with drug-eluting stents. HSR Proc Intensive Care Cardiovasc Anesth. 2012;4:153–167.PubMedPubMedCentral Dimitrova G, Tulman DB, Bergese SD. Perioperative management of antiplatelet therapy in patients with drug-eluting stents. HSR Proc Intensive Care Cardiovasc Anesth. 2012;4:153–167.PubMedPubMedCentral
12.
Zurück zum Zitat Ochoa-Cortes F, Linan-Rico A, Jacobson KA, Christofi FL. Potential for developing purinergic drugs for gastrointestinal diseases. Inflamm Bowel Dis. 2014;20:1259–1287.CrossRefPubMedPubMedCentral Ochoa-Cortes F, Linan-Rico A, Jacobson KA, Christofi FL. Potential for developing purinergic drugs for gastrointestinal diseases. Inflamm Bowel Dis. 2014;20:1259–1287.CrossRefPubMedPubMedCentral
13.
Zurück zum Zitat Vadlamudi HC, Yalavarthi PR, Balambhaigari RY, Vulava J. Receptors and ligands role in colon physiology and pathology. J Recept Signal Transduct Res. 2013;33:1–9.CrossRefPubMed Vadlamudi HC, Yalavarthi PR, Balambhaigari RY, Vulava J. Receptors and ligands role in colon physiology and pathology. J Recept Signal Transduct Res. 2013;33:1–9.CrossRefPubMed
14.
Zurück zum Zitat Xiang Z, Burnstock G. Distribution of P2Y6 and P2Y12 receptor: their colocalization with calbindin, calretinin and nitric oxide synthase in the guinea pig enteric nervous system. Histochem Cell Biol. 2006;125:327–336.CrossRefPubMed Xiang Z, Burnstock G. Distribution of P2Y6 and P2Y12 receptor: their colocalization with calbindin, calretinin and nitric oxide synthase in the guinea pig enteric nervous system. Histochem Cell Biol. 2006;125:327–336.CrossRefPubMed
15.
Zurück zum Zitat Linan-Rico A, Wunderlich JE, Grants IS, et al. Purinergic autocrine regulation of mechanosensitivity and serotonin release in a human EC model: ATP-gated P2X3 channels in EC are downregulated in ulcerative colitis. Inflamm Bowel Dis. 2013;19:2366–2379.CrossRefPubMedPubMedCentral Linan-Rico A, Wunderlich JE, Grants IS, et al. Purinergic autocrine regulation of mechanosensitivity and serotonin release in a human EC model: ATP-gated P2X3 channels in EC are downregulated in ulcerative colitis. Inflamm Bowel Dis. 2013;19:2366–2379.CrossRefPubMedPubMedCentral
16.
Zurück zum Zitat Harker LA, Boissel JP, Pilgrim AJ, Gent M. Comparative safety and tolerability of clopidogrel and aspirin: results from CAPRIE. CAPRIE Steering Committee and Investigators. Clopidogrel versus aspirin in patients at risk of ischaemic events. Drug Saf. 1999;21:325–335.CrossRefPubMed Harker LA, Boissel JP, Pilgrim AJ, Gent M. Comparative safety and tolerability of clopidogrel and aspirin: results from CAPRIE. CAPRIE Steering Committee and Investigators. Clopidogrel versus aspirin in patients at risk of ischaemic events. Drug Saf. 1999;21:325–335.CrossRefPubMed
17.
Zurück zum Zitat Chan FK, Ching JY, Hung LC, et al. Clopidogrel versus aspirin and esomeprazole to prevent recurrent ulcer bleeding. N Engl J Med. 2005;352:238–244.CrossRefPubMed Chan FK, Ching JY, Hung LC, et al. Clopidogrel versus aspirin and esomeprazole to prevent recurrent ulcer bleeding. N Engl J Med. 2005;352:238–244.CrossRefPubMed
19.
Zurück zum Zitat Lovell RM, Ford AC. Effect of gender on prevalence of irritable bowel syndrome in the community: systematic review and meta-analysis. Am J Gastroenterol. 2012;107:991–1000.CrossRefPubMed Lovell RM, Ford AC. Effect of gender on prevalence of irritable bowel syndrome in the community: systematic review and meta-analysis. Am J Gastroenterol. 2012;107:991–1000.CrossRefPubMed
20.
Zurück zum Zitat Schmulson M, Adeyemo M, Gutierrez-Reyes G, et al. Differences in gastrointestinal symptoms according to gender in Rome II positive IBS and dyspepsia in a Latin American population. Am J Gastroenterol. 2010;105:925–932.CrossRefPubMed Schmulson M, Adeyemo M, Gutierrez-Reyes G, et al. Differences in gastrointestinal symptoms according to gender in Rome II positive IBS and dyspepsia in a Latin American population. Am J Gastroenterol. 2010;105:925–932.CrossRefPubMed
22.
Zurück zum Zitat Linan-Rico A, Wunderlich JE, Enneking JT, et al. Neuropharmacology of purinergic receptors in human submucous plexus: involvement of P2X1, P2X2, P2X3 channels, P2Y and A3 metabotropic receptors in neurotransmission. Neuropharmacology. 2015;95:83–99.CrossRefPubMedPubMedCentral Linan-Rico A, Wunderlich JE, Enneking JT, et al. Neuropharmacology of purinergic receptors in human submucous plexus: involvement of P2X1, P2X2, P2X3 channels, P2Y and A3 metabotropic receptors in neurotransmission. Neuropharmacology. 2015;95:83–99.CrossRefPubMedPubMedCentral
23.
Zurück zum Zitat Jaspers FJ, Tielemans MM, von Rossums LG, et al. Gastrointestinal symptoms in low-dose aspirin users: a comparison between plain and buffered aspirin. Neth Heart J. 2014;22:107–112.CrossRef Jaspers FJ, Tielemans MM, von Rossums LG, et al. Gastrointestinal symptoms in low-dose aspirin users: a comparison between plain and buffered aspirin. Neth Heart J. 2014;22:107–112.CrossRef
25.
Zurück zum Zitat Grubišić V, Gulbransen BD. Enteric glial activity regulates secretomotor function in the mouse colon but does not acutely affect gut permeability. J Physiol. 2017;595:3409–3424.CrossRefPubMed Grubišić V, Gulbransen BD. Enteric glial activity regulates secretomotor function in the mouse colon but does not acutely affect gut permeability. J Physiol. 2017;595:3409–3424.CrossRefPubMed
26.
Zurück zum Zitat Bhave S, Gade A, Kang M, Hauser KF, Dewey WL, Akbarali HI. Connexin–purinergic signaling in enteric glia mediates the prolonged effect of morphine on constipation. FASEB J. 2017;31:2649–2660.CrossRefPubMed Bhave S, Gade A, Kang M, Hauser KF, Dewey WL, Akbarali HI. Connexin–purinergic signaling in enteric glia mediates the prolonged effect of morphine on constipation. FASEB J. 2017;31:2649–2660.CrossRefPubMed
27.
Zurück zum Zitat Dodds KN, Beckett EA, Evans SF, Grace PM, Watkins LR, Hutchinson MR. Glial contributions to visceral pain: implications for disease etiology and the female predominance of persistent pain. Transl Psychiatry. 2016;6:e888.CrossRefPubMedPubMedCentral Dodds KN, Beckett EA, Evans SF, Grace PM, Watkins LR, Hutchinson MR. Glial contributions to visceral pain: implications for disease etiology and the female predominance of persistent pain. Transl Psychiatry. 2016;6:e888.CrossRefPubMedPubMedCentral
28.
Zurück zum Zitat Gu N, Eyo UB, Murugan M, et al. Microglial P2Y12 receptors regulate microglial activation and surveillance during neuropathic pain. Brain Behav Immun. 2016;55:82–92.CrossRefPubMed Gu N, Eyo UB, Murugan M, et al. Microglial P2Y12 receptors regulate microglial activation and surveillance during neuropathic pain. Brain Behav Immun. 2016;55:82–92.CrossRefPubMed
30.
Zurück zum Zitat Lee SJ, Kwon JA, Cho SA, Jarrar YB, Shin JG. Effects of testosterone and 17beta-oestradiol on expression of the G protein-coupled receptor P2Y12 in megakaryocytic DAMI cells. Platelets. 2012;23:579–585.CrossRefPubMed Lee SJ, Kwon JA, Cho SA, Jarrar YB, Shin JG. Effects of testosterone and 17beta-oestradiol on expression of the G protein-coupled receptor P2Y12 in megakaryocytic DAMI cells. Platelets. 2012;23:579–585.CrossRefPubMed
32.
Zurück zum Zitat Linan-Rico A, Ochoa-Cortes F, Beyder A, et al. Mechanosensory signaling in enterochromaffin cells and 5-HT release: potential implications for gut inflammation. Front Neurosci. 2016;10:564.CrossRefPubMedPubMedCentral Linan-Rico A, Ochoa-Cortes F, Beyder A, et al. Mechanosensory signaling in enterochromaffin cells and 5-HT release: potential implications for gut inflammation. Front Neurosci. 2016;10:564.CrossRefPubMedPubMedCentral
Metadaten
Titel
Clopidogrel IBS Patients Have Higher Incidence of Gastrointestinal Symptoms Influenced by Age and Gender
verfasst von
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
Publikationsdatum
24.08.2017
Verlag
Springer US
Erschienen in
Digestive Diseases and Sciences / Ausgabe 10/2017
Print ISSN: 0163-2116
Elektronische ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-017-4707-7

Weitere Artikel der Ausgabe 10/2017

Digestive Diseases and Sciences 10/2017 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.