Influence of the Concomitant Use of Clopidogrel and Proton Pump Inhibitors on Adverse Cardiovascular Events in Korean Patients with Acute Coronary Syndrome

Clopidogrel에 Proton Pump Inhibitors 병용 시 급성 관동맥 증후군 환자의 심장관련 부작용에 미치는 영향

  • Kim, Su Hyun (Department of Pharmacy, Yeouido St. Mary's Hospital) ;
  • Lee, Yu Jeung (College of Pharmacy, Kangwon National University)
  • Received : 2013.12.12
  • Accepted : 2014.06.13
  • Published : 2014.06.30

Abstract

Purpose: Recent investigations suggest that the antiplatelet effect of clopidogrel may be decreased when this medication is taken together with certain proton pump inhibitors (PPIs). However, there has been no study conducted in Korea regarding the clinical effect of clopidogrel-PPI interaction. This study targeted patients who received stents to investigate the effect of the concomitant use of clopidogrel and PPIs on the occurrence of adverse cardiovascular events in Korean patients. Methods: The patients who received a stent insertion at the Yeouido St. Mary's Hospital between January 2010 and April 2011 were included. The patients were divided into two groups, clopidogrel and clopidogrel + PPI, and followed for 12 months after the date of stent insertion using prescription history and medical records. The recurrence rates of the cardiovascular events among the two patient groups were statistically analyzed. Results: There was no difference between the two groups in the basic characteristics of the 157 patients in the clopidogrel group and the 62 patients in the clopidogrel+PPI group. Simple logistic regression showed a significantly higher rate of re-hospitalization in the clopidogrel+PPI group (OR=1.893, 95% CI 1.040-3.445, p=0.037). However, the results of the multivariate logistic regression of the variables found to have statistical significance by crosstabulation showed no significant difference in the rate of adverse cardiovascular events or re-hospitalization between the two groups. Conclusions: There was no significant difference between the clopidogrel and clopidogrel+PPI group among new patients with cardiovascular stents with respect to the occurrence of revascularization procedures, stent thrombosis, or chest pain, or with respect to the re-hospitalization rate for all cardiovascular events.

Keywords

References

  1. Roger VL, Go AS, Lloyd-Jones DM, et al. Heart disease and stroke statistics--2012 update: a report from the American Heart Association. Circulation 2012; 125: e2-e220. https://doi.org/10.1161/CIR.0b013e31823ac046
  2. Schampaert E, Cohen EA, Schluter M, et al. The Canadian study of the sirolimus-eluting stent in the treatment of patients with long de novo lesions in small native coronary arteries (C-SIRIUS). J Am Coll Cardiol 2004; 43: 1110-5. https://doi.org/10.1016/j.jacc.2004.01.024
  3. Park SJ, Kim YH, Lee BK, et al. Sirolimus-eluting stent implantation for unprotected left main coronary artery stenosis: comparison with bare metal stent implantation. J Am Coll Cardiol 2005; 45: 351-6. https://doi.org/10.1016/j.jacc.2004.10.039
  4. Appleby CE, Mackie K, Dzavik V, et al. Late outcomes following percutaneous coronary interventions: results from a large, observational registry. Can J Cardiol 2010; 26: e218-24. https://doi.org/10.1016/S0828-282X(10)70411-6
  5. Kushner FG, Hand M, Smith SC, Jr., et al. 2009 Focused Updates: ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction (updating the 2004 Guideline and 2007 Focused Update) and ACC/ AHA/SCAI Guidelines on Percutaneous Coronary Intervention (updating the 2005 Guideline and. 2007 Focused Update): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 2009; 120: 2271-306. https://doi.org/10.1161/CIRCULATIONAHA.109.192663
  6. Yu T, Chen J, Chen R, et al. Biocontrol of blue and gray mold diseases of pear fruit by integration of antagonistic yeast with salicylic acid. Int J Food Microbiol 2007; 116: 339-45. https://doi.org/10.1016/j.ijfoodmicro.2007.02.005
  7. Stauffer JC, Goy JJ, Duvoisin N, et al. Dramatic effect of early clopidogrel administration in reducing mortality and MACE rates in ACS patients. Data from the Swiss registry AMIS-Plus. Swiss Med Wkly 2012; 142: w13573.
  8. 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: 2508-9. https://doi.org/10.1111/j.1538-7836.2006.02162.x
  9. Lau WC, Waskell LA, Watkins PB, et al. Atorvastatin reduces the ability of clopidogrel to inhibit platelet aggregation: a new drug-drug interaction. Circulation 2003; 107: 32-7. https://doi.org/10.1161/01.CIR.0000047060.60595.CC
  10. Fontana P, Dupont A, Gandrille S, et al. Adenosine diphosphate-induced platelet aggregation is associated with P2Y12 gene sequence variations in healthy subjects. Circulation 2003; 108: 989-95. https://doi.org/10.1161/01.CIR.0000085073.69189.88
  11. Hulot JS, Bura A, Villard E, et al. Cytochrome P450 2C19 loss-of-function polymorphism is a major determinant of clopidogrel responsiveness in healthy subjects. Blood 2006; 108: 2244-7. https://doi.org/10.1182/blood-2006-04-013052
  12. Ishizaki T, Horai Y. Review article: cytochrome P450 and the metabolism of proton pump inhibitors--emphasis on rabeprazole. Aliment Pharmacol Ther 1999; 13 Suppl 3: 27-36.
  13. Ho PM, Maddox TM, Wang L, et al. Risk of adverse outcomes associated with concomitant use of clopidogrel and proton pump inhibitors following acute coronary syndrome. JAMA 2009; 301: 937-44. https://doi.org/10.1001/jama.2009.261
  14. 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: 256-60. https://doi.org/10.1016/j.jacc.2007.06.064
  15. Jeremias A, Sylvia B, Bridges J, et al. Stent thrombosis after successful sirolimus-eluting stent implantation. Circulation 2004; 109: 1930-2. https://doi.org/10.1161/01.CIR.0000127105.99982.21
  16. Iakovou I, Schmidt T, Bonizzoni E, et al. Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents. JAMA 2005; 293: 2126-30. https://doi.org/10.1001/jama.293.17.2126
  17. Artang R, Dieter RS. Analysis of 36 reported cases of late thrombosis in drug-eluting stents placed in coronary arteries. Am J Cardiol 2007; 99: 1039-43. https://doi.org/10.1016/j.amjcard.2006.12.025
  18. Grines CL, Bonow RO, Casey DE, Jr., et al. Prevention of premature discontinuation of dual antiplatelet therapy in patients with coronary artery stents: a science advisory from the American Heart Association, American College of Cardiology, Society for Cardiovascular Angiography and Interventions, American College of Surgeons, and American Dental Association, with representation from the American College of Physicians. Catheter Cardiovasc Interv 2007; 69: 334-40. https://doi.org/10.1002/ccd.21124
  19. Abraham NS, Hlatky MA, Antman EM, et al. ACCF/ACG/ AHA 2010 Expert Consensus Document on the concomitant use of proton pump inhibitors and thienopyridines: a focused update of the ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use: a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents. Circulation 2010; 122: 2619-33. https://doi.org/10.1161/CIR.0b013e318202f701
  20. Hulot JS, Collet JP, Silvain J, et al. Cardiovascular risk in clopidogrel-treated patients according to cytochrome P450 2C19*2 loss-of-function allele or proton pump inhibitor coadministration: a systematic meta-analysis. J Am Coll Cardiol 2010; 56: 134-43. https://doi.org/10.1016/j.jacc.2009.12.071
  21. Siller-Matula JM, Jilma B, Schror K, et al. Effect of proton pump inhibitors on clinical outcome in patients treated with clopidogrel: a systematic review and metaanalysis. J Thromb Haemost 2010; 8: 2624-41. https://doi.org/10.1111/j.1538-7836.2010.04049.x
  22. Juurlink DN, Gomes T, Ko DT, et al. A population-based study of the drug interaction between proton pump inhibitors and clopidogrel. CMAJ 2009; 180: 713-8. https://doi.org/10.1503/cmaj.082001
  23. Rassen JA, Choudhry NK, Avorn J, et al. Cardiovascular outcomes and mortality in patients using clopidogrel with proton pump inhibitors after percutaneous coronary intervention or acute coronary syndrome. Circulation 2009; 120: 2322-9. https://doi.org/10.1161/CIRCULATIONAHA.109.873497
  24. Stockl KM, Le L, Zakharyan A, et al. Risk of rehospitalization for patients using clopidogrel with a proton pump inhibitor. Arch Intern Med 2010; 170: 704-10. https://doi.org/10.1001/archinternmed.2010.34
  25. van Boxel OS, van Oijen MG, Hagenaars MP, et al. Cardiovascular and gastrointestinal outcomes in clopidogrel users on proton pump inhibitors: results of a large Dutch cohort study. Am J Gastroenterol 2010; 105: 2430-6; quiz 7. https://doi.org/10.1038/ajg.2010.334
  26. Schmidt M, Johansen MB, Robertson DJ, et al. Concomitant use of clopidogrel and proton pump inhibitors is not associated with major adverse cardiovascular events following coronary stent implantation. Aliment Pharmacol Ther 2012; 35: 165-74. https://doi.org/10.1111/j.1365-2036.2011.04890.x
  27. Yasu T, Ikee R, Miyasaka Y, et al. Efficacy and safety of concomitant use of rabeprazole during dual-antiplatelet therapy with clopidogrel and aspirin after drug-eluting stent implantation: a retrospective cohort study. Yakugaku Zasshi 2010; 130: 1743-50. https://doi.org/10.1248/yakushi.130.1743
  28. Zuern CS, Geisler T, Lutilsky N, et al. Effect of comedication with proton pump inhibitors (PPIs) on postinterventional residual platelet aggregation in patients undergoing coronary stenting treated by dual antiplatelet therapy. Thromb Res 2010; 125: e51-4. https://doi.org/10.1016/j.thromres.2009.08.016
  29. Cuisset T, Frere C, Quilici J, et al. Comparison of omeprazole and pantoprazole influence on a high 150-mg clopidogrel maintenance dose the PACA (Proton Pump Inhibitors And Clopidogrel Association) prospective randomized study. J Am Coll Cardiol 2009; 54: 1149-53. https://doi.org/10.1016/j.jacc.2009.05.050
  30. Sibbing D, Morath T, Stegherr J, et al. Impact of proton pump inhibitors on the antiplatelet effects of clopidogrel. Thromb Haemost 2009; 101: 714-9.
  31. Kreutz RP, Stanek EJ, Aubert R, et al. Impact of proton pump inhibitors on the effectiveness of clopidogrel after coronary stent placement: the clopidogrel Medco outcomes study. Pharmacotherapy 2010; 30: 787-96. https://doi.org/10.1592/phco.30.8.787