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Does proton pump inhibitors treatment affect the risk of gastrointestinal bleeding in patients on novel antithrombotic therapy?


Authors: Škorňová I. 1;  Bolek T. 2;  Samoš M. 2;  Marko J. 1;  Vádelová Ľ. 2;  Žolková J. 2;  Lányiová Boleková M. 3;  Staško J. 1;  Mokáň M. 2
Authors‘ workplace: Národné centrum hemostázy a trombózy, Klinika hematológie a transfuziológie JLF UK a UN Martin 1;  I. Interná klinika JLF UK a UN Martin 2;  Radiologická klinika JLF UK a UN Martin 3
Published in: Gastroent Hepatol 2019; 73(4): 319-325
Category: Clinical and Experimental Gastroenterology: Review Article

Overview

Oral antithrombotic therapy significantly increases the risk of gastrointestinal bleeding in patients with acute coronary syndromes or atrial fibrillation. Administration of proton pump inhibitors together with antiplatelet and anticoagulant agents may reduce the risk of gastrointestinal bleeding. Several relatively novel antithrombotic agents have been introduced for patients with acute coronary syndromes (clopidogrel, prasugrel, and ticagrelor) or atrial fibrillation requiring long-term anticoagulation therapy (dabigatran, rivaroxaban, apixaban, and edoxaban). These agents might inhibit platelets or coagulation more than older agents; therefore, the need for gastroprotection might be even greater when these new agents are used for long-term antithrombotic therapy. Consequently, these agents are frequently administered together. This review article summarizes recently reported data about the impact of proton pump inhibitors on the risk of novel antithrombotic therapy-associated bleeding.

Submitted: 26. 6. 2019

Accepted: 13. 8. 2019

Conflict of Interest: The authors declare that the article/ manuscript complies with ethical standards, patient anonymity has been respected, and they state that they have no financial, advisory or other com mercial interests in relation to the subject matter.

Publication Ethics: This article/ manuscript has not been published or is currently be ing submitted for another review.

The authors agree to publish their name and e-mail in the published article/ manuscript.

Dedication: The article/ manuscript was supported by grant APVV no. 16-0020.

The Editorial Board declares that the manuscript met the ICMJE „uniform requirements“ for biomedical papers.

Keywords:

gastrointestinal bleeding – proton pump inhibitors – novel oral anticoagulants – ADP receptor blocker therapy


Sources

1. Nagata N, Niikura R, Yamada A et al. Acute middle gastrointestinal bleeding risk associated with NSAIDs, antithrombotic drugs, and PPIs: a multicenter case-control study. PLoS One 2016; 11 (3): e0151332. doi: 10.1371/journal.pone.0151332.

2. Khan R, Lopes RD, Neely ML et al. Characterising and predicting bleeding in high-risk patients with an acute coronary syndrome. Heart 2015; 101 (18): 1475–1484. doi: 10.1136/heartjnl-2014-307346.

3. Ďuriček M, Bánovčin P, Hyrdel R. Inhibítory protónovej pumpy vo svetle klinických študií a bezpečnostný profil ich dlhodobého užívania. Gastroent Hepatol 2018; 72 (5): 432–440. doi: 10.14735/amgh2018432.

4. CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee. Lancet 1996; 348 (9038): 1329–1339. doi: 10.1016/ s0140-6736 (96) 09457-3.

5. Tan VP, Yan BP, Kiernan TJ et al. Risk and management of upper gastrointestinal bleeding associated with prolonged dual-antiplatelet therapy after percutaneous coronary intervention. Cardiovasc Revasc Med 2009; 10 (1): 36–44. doi: 10.1016/j.carrev.2008.11.001.

6. Bhatt DL, Cryer BL, Contant CF et al. Clopidogrel with or without omeprazole in coronary artery disease. N Engl J Med 2010; 363 (20): 1909–1917. doi: 10.1056/NEJMoa1007964.

7. Wang Q, Ljung R, Lagergren J et al. Prognosis of concomitant users of clopidogrel and proton-pump inhibitors in a high-risk population for upper gastrointestinal bleeding. BMC Pharmacol Toxicol 2014; 15: 22. doi: 10.1186/2050-6511-15-22.

8. Gilard M, Arnaud B, Cornily JC et al. Influence of omeprazole on the antiplatelet action of clopidogrel associated with aspirin: the randomized, double-blind OCLA (Omeprazole CLopidogrel Aspirin) study. J Am Coll Cardiol 2008; 51 (3): 256–260. doi: 10.1016/j.jacc.2007.06.064.

9. Gilard M, Arnaud B, Le Gal G et al. Influence of omeprazol on the antiplatelet action of clopidogrel associated to aspirin. J Thromb Haemost 2006; 4 (11): 2508–2509. doi: 10.1111/ j.1538-7836.2006.02162.x.

10. Serbin MA, Guzauskas GF, Veenstra DL. Clopidogrel-proton pump inhibitor drug-drug interaction and risk of adverse clinical outcomes among PCI-treated ACS patients: a meta-analysis. J Manag Care Spec Pharm 2016; 22 (8): 939–947. doi: 10.18553/jmcp.2016.22.8. 939.

11. Siller-Matula JM, Jilma B, Schrör K et al. Effect of proton pump inhibitors on clinical outcome in patients treated with clopidogrel: a systematic review and meta-analysis. J Thromb Haemost 2010; 8 (12): 2624–2641. doi: 10.1111/j.1538-7836.2010.04049.x.

12. Niu Q, Wang Z, Zhang Y et al. Combination use of clopidogrel and proton pump inhibitors increases major adverse cardiovascular events in patients with coronary artery disease: a meta-analysis. J Cardiovasc Pharmacol Ther 2017; 22 (2): 142–152. doi: 10.1177/1074248416663647.

13. Demcsák A, Lantos T. Bálint ER et al. PPIs are not responsible for elevating cardiovascular risk in patients on clopidogrel-a systematic review and meta-analysis. Front Physiol 2018; 9: 1550. doi: 10.3389/fphys.2018.01550.

14. Yi X, Zhou Q, Wang C et al. Concomitant use of proton pump inhibitors and clopidogrel is not associated with adverse outcomes after ischemic stroke in chinese population. J Stroke Cerebrovasc Dis 2016; 25 (12): 2859–2867. doi: 10.1016/j.jstrokecerebrovasdis.2016.08.001.

15. Batchelor R, Kumar R, Gilmartin-Thomas JF et al. Systematic review with meta-analysis: risk of adverse cardiovascular events with proton pump inhibitors independent of clopidogrel. Aliment Pharmacol Ther 2018; 48 (8): 780–796. doi: 10.1111/apt.14955.

16. Bhatt DL, Cryer BL, Contant CF et al. Clopidogrel with or without omeprazole in coronary artery disease. N Engl J Med 2010; 363 (20): 1909–1917. doi: 10.1056/NEJMoa1007964.

17. Ogilvie BW, Yerino P, Kazmi F et al. The proton pump inhibitor, omeprazole, but not lansoprazole or pantoprazole, is a metabolism-dependent inhibitor of CYP2C19: implications for coadministration with clopidogrel. Drug Metab Dispos 2011; 39 (11): 2020–2033. doi: 10.1124/dmd.111.041293.

18. Angiolillo DJ, Gibson CM, Cheng S et al. Differential effects of omeprazole and pantoprazole on the pharmacodynamics and pharmacokinetics of clopidogrel in healthy subjects: randomized, placebo-controlled, crossover comparison studies. Clin Pharmacol Ther 2011; 89 (1): 65–74. doi: 10.1038/clpt.2010.219.

19. Bolek T, Samoš M, Šimonová R et al. Does pantoprazole affect the on-treatment platelet reactivity in patients with acute STEMI treated with ADP receptor blockers? A pilot prospective study. Am J Ther 2017; 24 (2): e162–e166. doi: 10.1097/MJT.0000000000000454.

20. Wiviott SD, Braunwald E, McCabe CH. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007; 357 (20): 2001–2015. 10.1056/NEJMoa0706482.

21. Chen HB, Zhang XL, Liang HB et al. Meta-analysis of randomized controlled trials comparing risk of major adverse cardiac events and bleeding in patients with prasugrel versus clopidogrel. Am J Cardiol 2015; 116 (3): 384–392. doi: 10.1016/j.amjcard.2015.04.054.

22. Jackson LR 2nd, Peterson ED, McCoy LA et al. Impact of proton pump inhibitor use on the comparative effectiveness and safety of prasugrel versus clopidogrel: insights from the treatment with adenosine diphosphate receptor inhibitors: longitudinal assessment of treatment patterns and events after acute coronary syndrome (TRANSLATE-ACS) study. J Am Heart Assoc 2016; 5 (10). doi: 10.1161/JAHA.116.003 824.

23. Chen CH, Yang JC, Uang YS et al. Differential inhibitory effects of proton pump inhibitors on the metabolism and antiplatelet activities of clopidogrel and prasugrel. Biopharm Drug Dispos 2012; 33 (5): 278–283. doi: 10.1002/bdd.1795.

24. Nicolau JC, Bhatt DL, Roe MT et al. Concomitant proton-pump inhibitor use, platelet activity, and clinical outcomes in patients with acute coronary syndromes treated with prasugrel versus clopidogrel and managed without revascularization: insights from the targeted platelet inhibition to clarify the optimal strategy to medically manage acute coronary syndromes trial. Am Heart J 2015; 170 (4): 683–694. doi: 10.1016/j.ahj.2015.05.017.

25. Goodman SG, Blare R, Pieper KS et al. Association of proton pump inhibitor use on cardiovascular outcomes with clopidogrel and ticagrelor: insights from the platelet inhibition and patient outcomes trial. Circulation 2012; 125 (8): 978–986. doi: 10.1161/ CIRCULATIONAHA.111.032912.

26. Becker RC, Bassand JP, Budaj A et al. Bleeding complications with the P2Y12 receptor antagonists clopidogrel and ticagrelor in the PLATelet inhibition and patient Outcomes (PLATO) trial. Eur Heart J 2011; 32 (23): 2933–2944. doi: 10.1093/eurheartj/ehr422.

27. Hoedemaker NP, Damman P, Ottervanger JP et al. Trends in cardiovascular and bleeding outcomesin acute coronary syndrome patients treated with or without proton pump inhibitors during the introduction of novel P2Y12 inhibitors: a five-year experience from a single-centre observational registry. Eur Heart J Cardiovasc Pharmacother 2019; 5 (3): 127–138. doi: 10.1093/ehjcvp/pvy030.

28. Teng R. Ticagrelor: pharmacokinetic, pharmacodynamic and pharmacogenetic profile: an update. Clin Pharmacokinet 2015; 54 (11): 1125–1138. doi: 10.1007/s40262-015-0290-2.

29. Connolly SJ, Ezekowitz MD, Yusuf S et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009; 361 (12): 1139–1151. doi: 10.1056/NEJMoa0905561.

30. Flack KF, Desai J, Kolb JM et al. Major gastrointestinal bleeding often is caused by occult malignancy in patients receiving warfarin or dabigatran to prevent stroke and systemic embolism from atrial fibrillation. Clin Gastroenterol Hepatol 2017; 15 (5): 682–690. doi: 10.1016/j.cgh.2016.10.011.

31. Chan EW, Lau WC, Leung WK et al. Prevention of dabigatran-related gastrointestinal bleeding with gastroprotective agents: a population-based study. Gastroenterology 2015; 149 (3): 586–595. doi: 10.1053/j.gastro.2015.05.002.

32. Ray WA, Chung CP, Murray KT et al. Association of oral anticoagulants and proton pump inhibitor cotherapy with hospitalization for upper gastrointestinal tract bleeding. JAMA 2018; 320 (21): 2221–2230. doi: 10.1001/jama.2018.17242.

33. Patel MR, Mahaffey KW, Garg J et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011; 365 (10): 883–891. doi: 10.1056/NEJMoa1009638.

34. Sherwood MW, Nessel CC, Hellkamp AS et al. Gastrointestinal bleeding in patients with atrial fibrillation treated with rivaroxaban or warfarin: ROCKET AF trial. J Am Coll Cardiol 2015; 66 (21): 2271–2281. doi: 10.1016/j.jacc.2015. 09.024.

35. Granger CB, Alexander JH, McMurray JJ et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011; 365 (11): 981–992. doi: 10.1056/NEJMoa1107039.

36. Miller CS, Dorreen A, Martel M et al. Risk of gastrointestinal bleeding in patients taking non-vitamin K antagonist oral anticoagulants: a systematic review and meta-analysis. Clin Gastroenterol Hepatol 2017; 15 (11): 1674–1683. doi: 10.1016/j.cgh.2017.04.031.

37. Giugliano RP, Ruff CT, Braunwald E et al. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2013; 369 (22): 2093–2104. doi: 10.1056/NEJMoa1310907.

38. Aisenberg J, Chatterjee-Murphy P, Friedman Flack K et al. Gastrointestinal bleeding with edoxaban versus warfarin: results from the ENGAGE AF-TIMI 48 trial (Effective anticoagulation with factor Xa next generation in atrial fibrillation-thrombolysis in myocardial infarction). Circ Cardiovasc Qual Outcomes 2018; 11 (5): e003998. doi: 10.1161/CIRCOUTCOMES.117.003998.

39. Veitch AM, Vanbiervliet G, Gershlick AH et al. Endoscopy in patients on antiplatelet or anticoagulant therapy, including direct oral anticoagulants: British Society of Gastroenterology (BSG) and European Society of Gastrointestinal Endoscopy (ESGE) guidelines. Endoscopy 2016; 48 (4): 385–402. doi: 10.1055/s-0042-102652.

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