High post-treatment platelet reactivity is associated with a high incidence of myonecrosis after stenting for non-ST elevation acute coronary syndromes

Thomas Cuisset; Corinne Frere; Jacques Quilici; Pierre-Emmanuel Morange; Lyassine Nait-Saidi; Christopher Mielot; Laurent Bali; Marc Lambert; Marie-Christine Alessi; Jean-Louis Bonnet

doi:10.1160/TH06-07-0362

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2007; 97(02): 282-287
DOI: 10.1160/TH06-07-0362

Cardiovascular Biology and Cell Signalling

Schattauer GmbH

High post-treatment platelet reactivity is associated with a high incidence of myonecrosis after stenting for non-ST elevation acute coronary syndromes

Authors

Thomas Cuisset

¹Department of Cardiology, CHU Timone, Marseille, France
Corinne Frere

²INSERM, UMR 626, Faculté de Médecine CHU Timone, Marseille, France
Jacques Quilici

¹Department of Cardiology, CHU Timone, Marseille, France
Pierre-Emmanuel Morange

²INSERM, UMR 626, Faculté de Médecine CHU Timone, Marseille, France
Lyassine Nait-Saidi

¹Department of Cardiology, CHU Timone, Marseille, France
Christopher Mielot

¹Department of Cardiology, CHU Timone, Marseille, France
Laurent Bali

¹Department of Cardiology, CHU Timone, Marseille, France
Marc Lambert

¹Department of Cardiology, CHU Timone, Marseille, France
Marie-Christine Alessi

²INSERM, UMR 626, Faculté de Médecine CHU Timone, Marseille, France
Jean-Louis Bonnet

¹Department of Cardiology, CHU Timone, Marseille, France

Abstract

Summary

High post-treatment platelet reactivity (HPPR= adenosine diphosphate [ADP] 10 µM-induced platelet aggregation > 70%) identifies low responders to dual antiplatelet therapy with increased risk of recurrent cardiovascular (CV) events after stenting for non-ST elevation acute coronary syndromes (NSTEACS). This study was designed to compare the incidence of periprocedural myocardial infarction (MI) after stenting for NSTEACS patients between non-responders to dual antiplatelet therapy defined by HPPR and normo-responders. One hundred ninety NSTE-ACS consecutive patients undergoing coronary stenting were included in this prospective study. They received 250 mg aspirin and a 600 mg loading dose of clopidogrel at least 12 hours (h) before percutaneous coronary intervention (PCI). A single post-treatment blood sample was obtained before PCI to analyze maximal intensity of ADP-induced platelet aggregation, and troponin levels were analyzed before PCI, and 12 and 24 h after PCI. Troponin I was considered elevated if > 0.4 ng/ ml. HPPR was present in 22% of patients (n=42). Periprocedural MI occurred significantly more frequently in patients with HPPR than in the normo-responders (43% vs. 24%, p=0.014). After being correlated with recurrent ischemic events after stenting for NSTE-ACS, the HPPR seems to be also a marker of increased risk of periprocedural MI for NSTE-ACS patients.

Keywords

Acute coronary syndromes - stenting - platelet reactivity - periprocedural myocardial infarction

Full Text

References

References
1 Yusuf S, Zhao F, Mehta SR. et al. 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.
2 Mehta SR, Yusuf S, Peters RJ et al. Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE study. Lancet 2001; 358: 527-5.
3 Wang TH, Bhatt DL, Topol E. Aspirin and clopidogrel resistance : an emerging clinical entity. Eur Heart J 2006; 27: 647-654.
4 Eikelboom JW, Hirsh J, Weitz JI. et al. Aspirin-resistant thromboxane biosynthesis and the risk of myocardial infarction, stroke, or cardiovascular death in patients at high risk for cardiovascular events. Circulation 2002; 105: 1650-1655.
5 Gum PA, Kottke-Marchant K, Welsh PA. et al. A prospective, blinded determination of the natural history of aspirin resistance among stable patients with cardiovascular disease. J Am Coll Cardiol 2003; 41: 961-965.
6 Chen WH, Lee PY, Ng W. et al. Aspirin resistance is associated with a high incidence of myonecrosis after non-urgent percutaneous coronary intervention despite clopidogrel pretreatment. J Am Coll Cardiol 2004; 43: 1122-1126.
7 Muller I, Besta F, Schulz C. et al. Prevalence of clopidogrel non-responders among patients with stable angina pectoris scheduled for elective coronary stent placement. Thromb Haemost 2003; 89: 783-787.
8 Barragan P, Bouvier JL, Roquebert PO. et al. Resistance to thienopyridines: clinical detection of coronary stent thrombosis by monitoring of vasodilator-stimulated phosphoprotein phosphorylation. Catheter Cardiovasc Interv 2003; 59: 295-302.
9 Gurbel PA, Bliden KP, Samara W. et al. Clopidogrel effect on platelet reactivity in patients with stent thrombosis: results of the CREST Study. J Am Coll Cardiol 2005; 46: 1827-1832.
10 Wenaweser P, Hess O. Stent thrombosis is associated with an impaired response to antiplatelet therapy. J Am Coll Cardiol 2005; 46: CS5–6.
11 Matetzky S, Shenkman B, Guetta V. et al. Clopidogrel resistance is associated with increased risk of recurrent atherothrombotic events in patients with acute myocardial infarction. Circulation 2004; 109: 3171-3175.
12 Cuisset T, Frere C, Quilici J. et al. High post-treatment platelet reactivity identified low-responders to dual antiplatelet therapy at increased risk of recurrent cardiovascular events after stenting for acute coronary syndrome. J Thromb Haemost 2006; 4: 542-549.
13 Hermann J. Peri-procedural myocardial injury: 2005 update. Eur Heart J 2005; 26: 2493-2519.
14 Rao AK, Pratt C, Berke A. et al. Thrombolysis in Myocardial Infarction (TIMI) Trial--phase I: hemorrhagic manifestations and changes in plasma fibrinogen and the fibrinolytic system in patients treated with recombinant tissue plasminogen activator and streptokinase. J Am Coll Cardiol 1988; 11: 1-11.
15 Garbarz E, Iung B, Lefevre G. et al. Frequency and pronostic value of cardiac troponin I elevation after coronary stenting. Am J Cardiol 1999; 84: 515-518.
16 Nageh T, Sherwood RA, Harris BM. et al. Pronostic role of cardiac troponin I after coronary percutaneous intervention in stable coronary disease. Heart 2005; 91: 1181-1185.
17 Smith Jr. SC, Feldman TE, Hirshfeld Jr JW. et al. ACC/AHA/SCAI 2005 Guideline Update for Percutaneous Coronary Intervention-Summary Article A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/SCAI Writing Committee to Update the 2001 Guidelines for Percutaneous Coronary Intervention). J Am Coll Cardiol 2006; 47: 216-235.
18 Steinhubl SR, Berger PB, Mann JT 3 rd,. et al Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial. J Am Med Assoc 2002; 288: 2411-2420.
19 Bertrand ME, Rupprecht HJ, Urban P. et al. Doubleblind study of the safety of clopidogrel with and 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: 624-629.
20 Kastrati A, von Beckerath N, Joost A. et al. Loading with 600 mg clopidogrel in patients with coronary artery disease with and without chronic clopidogrel therapy. Circulation 2004; 110: 1916-1919.
21 Gurbel PA, Bliden KP, Hayes KM. et al. The relation of dosing to clopidogrel responsiveness and the incidence of high post-treatment platelet aggregation in patients undergoing coronary stenting. J Am Coll Cardiol 2005; 45: 1392-1396.
22 Angiolillo DJ, Fernandez-Ortiz A, Bernardo E. et al. High clopidogrel loading dose during coronary stenting: effects on drug response and interindividual variability. Eur Heart J 2004; 25: 1903-1910.
23 Gurbel PA, Bliden KP, Zaman KA. et al. Clopidogrel loading with eptifibatide to arrest the reactivity of platelets: results of the Clopidogrel Loading With Eptifibatide to Arrest the Reactivity of Platelets (CLEAR PLATELETS) study. Circulation 2005; 111: 1153-1159.
24 von Beckerath N, Taubert D, Pogatsa-Murray G. et al. Absorption, metabolization, and antiplatelet effects of 300-, 600-, and 900-mg loading doses of clopidogrel: results of the ISAR-CHOICE (Intracoronary Stenting and Antithrombotic Regimen: Choose Between 3 High Oral Doses for Immediate Clopidogrel Effect) Trial. Circulation 2005; 112: 2946-2950.
25 Patti G, Colonna G, Pasceri V. et al. Randomized trial of high loading dose of clopidogrel for reduction of periprocedural myocardial infarction in patients undergoing coronary intervention. Results from the ARMYDA-2 (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty) Study. Circulation 2005; 111: 2099-2106.
26 Cuisset T, Frere C, Quilici J. et al. Benefit of a 600 mg loading dose of clopidogrel on platelet reactivity and clinical outcomes in patients with non-ST elevation Acute Coronary Syndrome undergoing coronary stenting. J Am Coll Cardiol. 2006. in press.
27 Lev EI, Patel RT, Maresh KJ. et al. Aspirin and clopidogrel drug response in patients undergoing percutaneous coronary intervention: the role of dual drug resistance. J Am Coll Cardiol 2006; 47: 27-33.
28 Kastrati A, Mehilli J, Neumann FJ. et al. Abciximab in patients with acute coronary syndromes undergoing percutaneous coronary intervention after clopidogrel pretreatment: the ISAR-REACT 2 randomized trial. J Am Med Assoc 2006; 295: 1531-1538.
29 Jernberg T, Payne CD, Winters KJ. et al. Prasugrel achieves greater inhibition of platelet agregation and a lower rate of non-responders compared with clopidogrel in aspirin-treated patients with stable coronary artery disease. Eur Heart J 2006; 27: 1166-1173.