Advertisement

Cardiovascular Intervention and Therapeutics

, Volume 29, Issue 2, pp 123–133 | Cite as

Japanese postmarketing surveillance of clopidogrel for patients with non-ST-segment-elevation acute coronary syndrome indicated for percutaneous coronary intervention (J-PLACE NSTE-ACS)

  • Yoshihiro Morino
  • Junya Ako
  • Masayuki Kobayashi
  • Masato Nakamura
Original Article

Abstract

Clopidogrel in combination with aspirin has been a standard therapy for patients who have undergone percutaneous coronary intervention. The present study was conducted as a postmarketing surveillance, for the purpose of assessing the safety and efficacy of clopidogrel in real clinical practice in patients with non-ST-segment-elevation acute coronary syndrome (NSTE-ACS). Subjects were registered between March 2008 and December 2010, and as a result, patients not only with NSTE-ACS but also other types of ischemic heart diseases were enrolled. Data on off-label subjects were used only in safety evaluation. After excluding patients with inappropriate clinical report forms, 3,673 patients with non-ST-segment-elevation myocardial infarction, unstable angina, STEMI, stable angina, or old myocardial infarction were observed for safety evaluation. Efficacy was assessed in 2,562 of the 3,673 patients with NSTE-ACS. Aspirin was concomitantly prescribed to 3,615/3,673 (98.6 %) of the safety group, and 2,374/3,673 (64.6 %) received a loading dose of clopidogrel. During a maximum follow-up period of 12 months, 397 (10.8 %) of the 3,673 patients experienced adverse drug reactions (ADRs), of whom 145 (4.0 %) had serious conditions, as classified by the investigators. The most frequently observed ADRs were hepatobiliary and gastrointestinal disorders. Bleeding adverse events were observed in 138 patients (3.8 %) and 80 cases (2.2 %) were considered as serious. The 1-year cumulative incidence of major adverse cardiovascular events and major adverse cardiac and cerebrovascular events in the patients with NSTE-ACS were estimated to be 11.6 and 12.2 %, respectively. Serious AEs that substantially affect the safety profile of clopidogrel were not confirmed.

Keywords

Clopidogrel Postmarketing surveillance NSTE-ACS 

Notes

Acknowledgments

This study was funded by Sanofi K.K. The authors thank all the investigators, staffs, and patients who contributed to this postmarketing surveillance.

Conflict of interest

YM, JA and MN received remuneration (e.g. lecture fees) from Sanofi K.K. YM and MN received research funding from Sanofi K.K. MK is an employee of Sanofi K.K.

Supplementary material

12928_2013_229_MOESM1_ESM.doc (406 kb)
Supplementary material 1 (DOC 406 kb)

References

  1. 1.
    Yusuf S, Zhao F, Mehta SR, Chrolavicius S, Tognoni G, Fox KK. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med. 2001;345:494–502.PubMedCrossRefGoogle Scholar
  2. 2.
    Chen ZM, Jiang LX, Chen YP, Xie JX, Pan HC, Peto R, COMMIT (Clopidogrel and Metoprolol in Myocardial Infarction trial) Collaborative Group, et al. Addition of clopidogrel to aspirin in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial. Lancet. 2005;366:1607–21.PubMedCrossRefGoogle Scholar
  3. 3.
    Fox KAA, Mehta SR, Peters R, Zhao F, Lakkis N, Gersh BJ, et al. Benefits and risks of the combination of clopidogrel and aspirin in patients undergoing surgical revascularization for non-ST elevation acute coronary syndrome: the Clopidogrel in Unstable Angina to Prevent Recurrent Ischemic Events (CURE) trial. Circulation. 2004;110:1202–8.PubMedCrossRefGoogle Scholar
  4. 4.
    Sabatine M, Cannon C, Gibson C, Lopez-Sendon J, Montalescot G, Theroux P, et al. Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation. N Engl J Med. 2005;352:1179–89.PubMedCrossRefGoogle Scholar
  5. 5.
    Wallentin L, Becker RC, Butaji A, Cannon CP, Emanuelsson H, Held C, For the PLATO Investigators, et al. Ticagrelol versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009;361:1045–57.PubMedCrossRefGoogle Scholar
  6. 6.
    Smith SC Jr, Benjamin EJ, Bonow RO, Braun LT, Creager MA, Franklin BA, et al. AHA/ACCF secondary prevention and risk reduction therapy for patients with coronary and other atherosclerotic vascular disease: 2011 update: a guideline from American Heart Association and American College of Cardiology Foundation. Circulation. 2011;124:2473–85.Google Scholar
  7. 7.
    King SB III, Smith SC Jr, Hirshfeld JW Jr, Jacobs AK, Morrison DA, Williams DO, et al. Writing Group to review new evidence and update the ADD/AHA/SCAI 2005 Guideline Update for Percutaneous Coronary Intervention, writing on behalf of the 2005 Writing Committee. 2007 focused update of the ACC/AHA/SCAI 2005 guideline update for percutaneous coronary intervention: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guideline. Circulation. 2008;117:261–95.PubMedCrossRefGoogle Scholar
  8. 8.
    Maussa I, Oetgen M, Roubin G, Colombo A, Wang X, Iyer S, et al. Effectiveness of clopidogrel and aspirin versus ticlopidine and aspirin in preventing stent thrombosis after coronary stent implantation. Circulation. 1999;99:2364–6.CrossRefGoogle Scholar
  9. 9.
    Brertrand ME, Rupprecht H-J, Urban P, Gershlick AH, For the CLASSICS Investigators. Double-blind study of the safety of clopidogrel with or without a loading dose in combination with aspirin compared with ticlopidine in combination with aspirin after coronary stenting: the Clopidogrel Aspirin Stent International Cooperative Study (CLASSICS). Circulation. 2000;102:624–9.CrossRefGoogle Scholar
  10. 10.
    Fischer MJ, Ho PM, McDermott K, Lowy E, Parikh CR. Chronic kidney disease is associated with adverse outcomes among elderly patients taking clopidogrel after hospitalization for acute coronary syndrome. BMC Nephrol. 2013;14:107.PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Palmer SC, Di Micco L, Razavian M, Craig JC, Perkovic V, Pellegrini F, et al. Effects of antiplatelet therapy on mortality and cardiovascular and bleeding outcomes in persons with chronic kidney disease: a systematic review and meta-analysis. Ann Intern Med. 2012;156:445–59.PubMedCrossRefGoogle Scholar
  12. 12.
    Keltai M, Tonelli M, Mann JF, Sitkei E, Lewis BS, Hawken S, et al. Renal function and outcomes in acute coronary syndrome: impact of clopidogrel. Eur J Cardiovasc Prev Rehabil. 2007;14:312–8.PubMedCrossRefGoogle Scholar
  13. 13.
    Basra SS, Tsai P, Lakkis NM. Safety and efficacy of antiplatelet and antithrombotic therapy in acute coronary syndrome patients with chronic kidney disease. J Am Coll Cardiol. 2011;58:2263–9.PubMedCrossRefGoogle Scholar
  14. 14.
    Best PJ, Steinhubl SR, Berger PB, Dasgupta A, Brennan DM, Szczech LA, et al. The efficacy and safety of short- and long-term dual antiplatelet therapy in patients with mild or moderate chronic kidney disease: results from the Clopidogrel for the Reduction of Events During Observation (CREDO) trial. Am Heart J. 2008;155:687–93.PubMedCrossRefGoogle Scholar
  15. 15.
    Fox CS, Muntner P, Chen AY, Alexander KP, Roe MT, Cannon CP, et al. Use of evidence-based therapies in short-term outcomes of ST-segment elevation myocardial infarction and non-ST-segment elevation myocardial infarction in patients with chronic kidney disease: a report from the National Cardiovascular Data Acute Coronary Treatment and Intervention Outcomes Network registry. Circulation. 2010;121:357–65.PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Cadiou G, Adam M, Caussin M, Landrin I, Mariette N, Capet C, et al. Antiplatelet drugs in the elderly: prescriptions often inappropriate and reduced tolerance by associated diseases and drugs. Fundam Clin Pharmacol. 2012;26:307–13.PubMedCrossRefGoogle Scholar
  17. 17.
    Dewilde WJ, Oirbans T, Verheugt FW, Kelder JC, De Smet BJ, Herrman JP, et al. Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomised, controlled trial. Lancet. 2013;381:1107–15.PubMedCrossRefGoogle Scholar
  18. 18.
    Smith JG, Wieloch M, Koul S, Braun OÖ, Lumsden J, Rydell E, et al. Triple antithrombotic therapy following an acute coronary syndrome: prevalence, outcomes and prognostic utility of the HAS-BLED score. EuroIntervention. 2012;8:672–8.PubMedCrossRefGoogle Scholar
  19. 19.
    Ho PM, Maddox TM, Wang L, Fihn SD, Jesse RL, Peterson ED, 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.PubMedCrossRefGoogle Scholar
  20. 20.
    Juurlink DN, Gomes T, Ko DT, Szmitko PE, Austin PC, Tu JV, et al. A population-based study of the drug interaction between proton pump inhibitors and clopidogrel. Can Med Assoc J. 2009;180:713–8.CrossRefGoogle Scholar
  21. 21.
    Huang CC, Chen YC, Leu HB, Chen TJ, Lin SJ, Chan WL, et al. Risk of adverse outcomes in Taiwan associated with concomitant use of clopidogrel and proton pump inhibitors in patients who received percutaneous coronary intervention. Am J Cardiol. 2010;105:1705–9.PubMedCrossRefGoogle Scholar
  22. 22.
    Food and Drug Administration. Drug safety communication: Reduced effectiveness of Plavix (clopidogrel) in patients who are poor metabolizers of the drug. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm203888.htm (Accessed 13 Aug 2013).
  23. 23.
    Kimura T, Morimoto T, Furukawa Y, Nakagawa Y, Kadota K, Iwabuchi M, et al. Association of the use of proton pump inhibitors with adverse cardiovascular and bleeding outcomes after percutaneous coronary intervention in the Japanese real world clinical practice. Cardiovasc Interv Ther. 2011;26:222–33.PubMedCrossRefGoogle Scholar
  24. 24.
    Jiang Z, Wu H, Duan Z, Wang Z, Hu K, Ye F, et al. Proton-pump inhibitors can decrease gastrointestinal bleeding after percutaneous coronary intervention. Clin Res Hepatol Gastroenterol. 2013 (Epub ahead of print).Google Scholar
  25. 25.
    Ohkubo K, Kobayashi Y, Nakamura Y, Miyazaki A. Incidence of side-effects of dual antiplatelet therapy with clopidogrel and aspirin after coronary stent implantation. Cardiovasc Interv Ther. 2011;26:33–7.PubMedCrossRefGoogle Scholar
  26. 26.
    Isshiki T, Kimura T, Ueno T, Nakamura M, Igarashi K, Yokoi H, et al. Clopidogrel trial in patients with elective percutaneous coronary intervention for stable angina and old myocardial infarction (CLEAN): safety and efficacy study of clopidogrel compared to ticlopidine in Japanese patients. Int Heart J. 2012;53:91–101.PubMedCrossRefGoogle Scholar
  27. 27.
    Fukuuchi Y, Tohgi H, Okudera T, Ikeda Y, Miyanaga Y, Uchiyama S, et al. A randomized, double-blind study comparing the safety and efficacy of clopidogrel versus ticlopidine in Japanese patients with noncardioembolic cerebral infarction. Cerebrovasc Dis. 2008;25:40–9.PubMedCrossRefGoogle Scholar
  28. 28.
    Uchiyama S, Fukuuchi Y, Yamaguchi T. The safety and efficacy of clopidogrel versus ticlopidine in Japanese stroke patients: combined results of two phase III, multicenter, randomized clinical trials. J Neurol. 2009;256:888–97.PubMedCrossRefGoogle Scholar
  29. 29.
    Shigematsu H, Komori K, Tanemoto K, Harada Y, Nakamura M. Clopidogrel for atherothrombotic event management in patients with peripheral arterial disease (COOPER) study: safety and efficacy of clopidogrel versus ticlopidine in Japanese patients. Ann Vasc Dis. 2012;5:364–75.PubMedCentralPubMedCrossRefGoogle Scholar
  30. 30.
    Daida H, Miyauchi K, Ogawa H, Yokoi H, Matsumoto M, Kitakaze M, et al. Management and two-year long-term clinical outcomes of patients with acute coronary syndrome in Japan: prevention of atherothrombotic incidents following ischemic coronary attack (PACIFIC) registry. Circ J. 2013;77:934–43.PubMedCrossRefGoogle Scholar

Copyright information

© Japanese Association of Cardiovascular Intervention and Therapeutics 2013

Authors and Affiliations

  • Yoshihiro Morino
    • 1
  • Junya Ako
    • 2
  • Masayuki Kobayashi
    • 3
  • Masato Nakamura
    • 4
  1. 1.Division of Cardiology, Department of Internal MedicineIwate Medical UniversityMoriokaJapan
  2. 2.Department of Cardiovascular MedicineKitasato UniversityKanagawaJapan
  3. 3.Medical OperationsTokyoJapan
  4. 4.Division of Cardiovascular MedicineToho University Ohashi Medical CenterTokyoJapan

Personalised recommendations