Heart and Vessels

, Volume 27, Issue 1, pp 106–109

A case of subacute thrombosis associated with clopidogrel resistance after implantation of a zotarolimus-eluting stent

  • Mizuhiro Arima
  • Atsushi Matsuda
  • Manabu Nitta
  • Keiko Yoshida
  • Makoto Shimizu
Case Report


A 73-year-old woman was admitted to our hospital with anterior acute myocardial infarction due to subacute thrombosis after coronary stenting with a zotarolimus-eluting stent (ZES), which is a newly developed drug-eluting stent that has been widely used since May 2009 in Japan. Five days before, she underwent implantation with a ZES in the left anterior descending artery due to stable angina pectoris. After stenting, the intravascular ultrasonography showed no malapposition from the proximal to the distal edge of the stent. She received aspirin 100 mg/day and clopidogrel 75 mg/day from 2 weeks before the stent was implanted. When we investigated the single nucleotide polymorphisms of CYP2C19 in this patient, both CYP2C19*2 and CYP2C19*3 were detected, and she was classified as a poor metabolizer. This report is the first to describe subacute stent thrombosis following the implantation of a newly developed ZES in a Japanese patient, which may be related to clopidogrel resistance.


Clopidogrel resistance Acute coronary syndrome Percutaneous coronary intervention Drug-eluting stent 


  1. 1.
    Geisler T, Langer H, Wydymus M, Göhring K, Zürn C, Bigalke B, Stellos K, May AE, Gawaz M (2006) Low response to clopidogrel is associated with cardiovascular outcome after coronary stent implantation. Eur Heart J 27:2420–2425PubMedCrossRefGoogle Scholar
  2. 2.
    Hulot JS, Bura A, Villard E, Azizi M, Remones V, Goyenvalle C, Aiach M, Lechat P, Gaussem P (2006) Cytochrome P450 2C19 loss-of-function polymorphism is a major determinant of clopidogrel responsiveness in healthy subjects. Blood 108:2244–2247PubMedCrossRefGoogle Scholar
  3. 3.
    Kimura T, Morimoto T, Nakagawa Y, Tamura T, Kadota K, Yasumoto H, Nishikawa H, Hiasa Y, Muramatsu T, Meguro T, Inoue N, Honda H, Hayashi Y, Miyazaki S, Oshima S, Honda T, Shiode N, Namura M, Sone T, Nobuyoshi M, Kita T, Mitsudo K, for the j-Cypher Registry Investigators (2009) Antiplatelet therapy and stent thrombosis after sirolimus-eluting stent implantation. Circulation 119:987–995PubMedCrossRefGoogle Scholar
  4. 4.
    Aoki J, Lansky AJ, Mehran R, Moses J, Bertrand ME, McLaurin BT, Cox DA, Lincoff AM, Ohman EM, White HD, Parise H, Leon MB, Stone GW (2009) Early stent thrombosis in patients with acute coronary syndromes treated with drug-eluting and bare metal stents: the Acute Catheterization and Urgent Intervention Triage Strategy Trial. Circulation 119:687–698PubMedCrossRefGoogle Scholar
  5. 5.
    Cook S, Windecker S (2009) Early stent thrombosis: past, present, and future. Circulation 119:657–659PubMedCrossRefGoogle Scholar
  6. 6.
    Simon T, Verstuyft C, Mary-Krause M, Quteineh L, Drouet E, Méneveau N, Steg PG, Ferrières J, Danchin N, Becquemont L, for the French Registry of Acute ST-Elevation, Non–ST-Elevation Myocardial Infarction (FAST-MI) Investigators (2009) Genetic determinants of response to clopidogrel and cardiovascular events. N Engl J Med 360:363–375PubMedCrossRefGoogle Scholar
  7. 7.
    Mega JL, Close SL, Wiviott SD, Shen L, Hockett RD, Brandt JT, Walker JR, Antman EM, Macias W, Braunwald E, Sabatine MS (2009) Cytochrome P-450 polymorphisms and response to clopidogrel. N Engl J Med 360:354–362PubMedCrossRefGoogle Scholar
  8. 8.
    Collet JP, Hulot JS, Pena A, Villard E, Esteve JB, Silvain J, Payot L, Brugier D, Cayla G, Beygui F, Bensimon G, Brentano F, Montalescot G (2009) Cytochrome P450 2C19 polymorphism in young patients treated with clopidogrel after myocardial infarction: a cohort study. Lancet 373:309–317PubMedCrossRefGoogle Scholar
  9. 9.
    Brackbill M, Kidd RS, Abdoo AD, Warner JG, Harralson AF (2009) Frequency of CYP3A4, CYP3A5, CYP2C9, and CYP2C19 variant alleles in patients receiving clopidogrel that experience repeat acute coronary syndrome. Heart Vessels 24:73–78PubMedCrossRefGoogle Scholar
  10. 10.
    Desta Z, Zhao X, Shin JG, Flockhart DA (2002) Clinical significance of the cytochrome P450 2C19 genetic polymorphism. Clin Pharmacokinet 41:913–958PubMedCrossRefGoogle Scholar
  11. 11.
    Trenk D, Hochholzer W, Fromm MF, Chialda LE, Pahl A, Valina CM, Stratz C, Schmiebusch P, Bestehorn HP, Büttner HJ, Neumann FJ (2008) Cytochrome P450 2C19 681G>A polymorphism and high on-clopidogrel platelet reactivity associated with adverse 1-year clinical outcome of elective percutaneous coronary intervention with drug-eluting or bare-metal stents. J Am Coll Cardiol 51:1925–1934Google Scholar
  12. 12.
    Giusti B, Gori AM, Marcucci R, Saracini C, Sestini I, Paniccia R, Buonamici P, Antoniucci D, Abbate R, Gensini GF (2009) Relation of cytochrome P450 2C19 loss-of-function polymorphism to occurrence of drug-eluting coronary stent thrombosis. Am J Cardiol 103:806–811PubMedCrossRefGoogle Scholar
  13. 13.
    Shuldiner AR, O’Connell JR, Bliden KP, Gandhi A, Ryan K, Horenstein RB, Damcott CM, Pakyz R, Tantry US, Gibson Q, Pollin TI, Post W, Parsa A, Mitchell BD, Faraday N, Herzog W, Gurbel PA (2009) Association of cytochrome P450 2C19 genotype with the antiplatelet effect and clinical efficacy of clopidogrel therapy. JAMA 302:849–857PubMedCrossRefGoogle Scholar
  14. 14.
    Gilard M, Arnaud B, Le Gal G, Abgrall JF, Boschat J (2006) Influence of omeprazol on the antiplatelet action of clopidogrel associated to aspirin. J Thromb Haemost 4:2508–2509PubMedCrossRefGoogle Scholar
  15. 15.
    Angiolillo DJ, Capranzano P, Goto S, Aslam M, Desai B, Charlton RK, Suzuki Y, Box LC, Shoemaker SB, Zenni MM, Guzman LA, Bass TA (2008) A randomized study assessing the impact of cilostazol on platelet function profiles in patients with diabetes mellitus and coronary artery disease on dual antiplatelet therapy: results of the OPTIMUS-2 study. Eur Heart J 29:2202–2211PubMedCrossRefGoogle Scholar
  16. 16.
    Chen KY, Rha SW, Li YJ, Poddar KL, Jin Z, Minami Y, Wang L, Kim EJ, Park CG, Seo HS, Oh DJ, Jeong MH, Ahn YK, Hong TJ, Kim YJ, Hur SH, Seong IW, Chae JK, Cho MC, Bae JH, Choi DH, Jang YS, Chae IH, Kim CJ, Yoon JH, Chung WS, Seung KB, Park SJ, for the Korea Acute Myocardial Infarction Registry Investigators (2009) Triple versus dual antiplatelet therapy in patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. Circulation 119:3207–3214Google Scholar
  17. 17.
    Sakakura K, Kubo N, Ako J, Ikeda N, Funayama H, Hirahara T, Wada H, Sugawara Y, Yasu T, Kawakami M, Momomura S (2009) Clinical features of early recurrent myocardial infarction. Heart Vessels 24:347–351PubMedCrossRefGoogle Scholar

Copyright information

© Springer 2011

Authors and Affiliations

  • Mizuhiro Arima
    • 1
  • Atsushi Matsuda
    • 1
  • Manabu Nitta
    • 1
  • Keiko Yoshida
    • 1
  • Makoto Shimizu
    • 1
  1. 1.Department of CardiologyInternational Goodwill HospitalKanagawaJapan

Personalised recommendations