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Thromb Haemost 2007; 98(04): 838-843
DOI: 10.1160/TH07-04-0296
Cardiovascular Biology and Cell Signalling
Schattauer GmbH

ADP-induced platelet aggregation and platelet reactivity index VASP are good predictive markers for clinical outcomes in non-ST elevation acute coronary syndrome

Corinne Frere
1   INSERM, UMR 626, Faculté de Médecine CHU Timone, Marseille, France
,
Thomas Cuisset
2   Department of Cardiology, CHU Timone, Marseille, France
,
Jacques Quilici
2   Department of Cardiology, CHU Timone, Marseille, France
,
Laurence Camoin
3   Laboratory of Haematology, CHU Conception, Marseille, France
,
Joseph Carvajal
1   INSERM, UMR 626, Faculté de Médecine CHU Timone, Marseille, France
,
Pierre Emmanuel Morange
1   INSERM, UMR 626, Faculté de Médecine CHU Timone, Marseille, France
,
Marc Lambert
2   Department of Cardiology, CHU Timone, Marseille, France
,
Irène Juhan-Vague
1   INSERM, UMR 626, Faculté de Médecine CHU Timone, Marseille, France
,
Jean-Louis Bonnet
2   Department of Cardiology, CHU Timone, Marseille, France
,
Marie-Christine Alessi
1   INSERM, UMR 626, Faculté de Médecine CHU Timone, Marseille, France
› Author Affiliations
Further Information

Publication History

Received 23 April 2007

Accepted after resubmission 08 July 2007

Publication Date:
01 December 2017 (online)

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Summary

Clopidogrel responsiveness has been proposed to be involved in recurrent ischemic events after stenting for non-ST elevation acute coronary syndromes (NSTE ACS). However, its biological definition is not consensual. We assess the value ofADP-induced platelet aggregation (ADP-Ag) and platelet reactivity indexVASP (PRI VASP) in predicting recurrent ischemic events in patients with NSTE ACS undergoing percutaneous coronary intervention (PCI). We studied 195 consecutive NSTE ACS patients undergoing PCI after a 600 mg loading dose of clopidogrel. ADPAg and PRI VASP were analysed. The primary end-point was recurrent ischemic events within 30 days of PCI. It occurred in 14 patients (7%). Construction of ROC curves to examine the value of predictive models showed that sensitivity and specificity for primary endpoint were 79% and 76%, respectively, for a maximal intensity of ADP-Ag ≥70%, 93% and 50% for PRIVASP> 53%. The positive and negative predictive values were 21% and 98%, respectively, for ADP-Ag ≥70%, 12% and 99% for PRIVASP> 53%. In patients with NSTE ACS undergoing PCI, ADP-Ag and PRI VASP identify low responders to clopidogrel with an increased risk of recurrent ischemic events with respective cut-off values of 70% and 53%.

Keywords

Clopidogrel response - platelet aggregation - VASP - acute coronary syndrome - coronary stenting
 

  • References

  • 1 Yusuf S. 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.
    CrossrefPubMedGoogle Scholar
  • 2 Mehta SR. 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: 527-533.
    CrossrefPubMedGoogle Scholar
  • 3 Bertrand ME. et al. Double-blind 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.
    CrossrefPubMedGoogle Scholar
  • 4 Gurbel PA. et al. Clopidogrel for coronary stenting: response variability, drug resistance, and the effect of pretreatment platelet reactivity.. Circulation 2003; 107: 2908-2913.
    CrossrefPubMedGoogle Scholar
  • 5 Angiolillo DJ. et al. Identification of low responders to a 300-mg clopidogrel loading dose in patients undergoing coronary stenting.. Thromb Res 2005; 115: 101-108.
    CrossrefPubMedGoogle Scholar
  • 6 Jaremo P. et al. Individual variations of platelet inhibition after loading doses of clopidogrel.. J Intern Med 2002; 252: 233-238.
    CrossrefPubMedGoogle Scholar
  • 7 Muller I. 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.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 8 Serebruany VL. et al. Variability in platelet responsiveness to clopidogrel among 544 individuals.. J Am Coll Cardiol 2005; 45: 246-251.
    CrossrefPubMedGoogle Scholar
  • 9 Angiolillo DJ. et al. Variability in individual responsiveness to clopidogrel: clinical implications, management, and future perspectives.. J Am Coll Cardiol. 2007; 49: 1505-1516.
    CrossrefPubMedGoogle Scholar
  • 10 Wang TH. et al. Aspirin and clopidogrel resistance: an emerging clinical entity.. Eur Heart J 2006; 27: 647-654.
    CrossrefPubMedGoogle Scholar
  • 11 Barragan P. 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.
    CrossrefPubMedGoogle Scholar
  • 12 Gurbel PA. et al. Platelet reactivity in patients and recurrent events post-stenting: results of the PREPARE POST-STENTING Study.. J Am Coll Cardiol 2005; 46: 1820-1826.
    CrossrefPubMedGoogle Scholar
  • 13 Gurbel PA. 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.
    CrossrefPubMedGoogle Scholar
  • 14 Wenaweser P, Hess O. Stent thrombosis is associated with an impaired response to antiplatelet therapy.. J Am Coll Cardiol 2005; 46: CS5-6.
    CrossrefPubMedGoogle Scholar
  • 15 Matetzky S. et al. Clopidogrel resistance is associated with increased risk of recurrent atherothrombotic events in patients with acute myocardial infarction.. Circulation 2004; 109: 3171-3175.
    CrossrefPubMedGoogle Scholar
  • 16 Cuisset T. 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.
    CrossrefPubMedGoogle Scholar
  • 17 Cuisset T. et al. High post-treatment platelet reactivity is associated with high incidence of myonecrosis after stenting for non-ST elevation acute coronary syndromes.. Thromb Haemost 2007; 97: 282-287.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 18 Geisler T. et al. Low response to clopidogrel is associated with cardiovascular outcome after coronary stent implantation.. Eur Heart J 2006; 27: 2420-2425.
    CrossrefPubMedGoogle Scholar
  • 19 Hochholzer W. et al. Impact of the degree of peri-interventional platelet inhibition after loading with clopidogrel on early clinical outcome of elective coronary stent placement.. J Am Coll Cardiol 2006; 48: 1742-1750.
    CrossrefPubMedGoogle Scholar
  • 20 Bliden KP. et al. Increased risk in patients with high platelet aggregation receiving chronic clopidogrel therapy undergoing percutaneous coronary intervention: is the current antiplatelet therapy adequate?. J Am Coll Cardiol 2007; 49: 657-666.
    CrossrefPubMedGoogle Scholar
  • 21 Aleil B. et al. Flow cytometric analysis of intraplatelet VASP phosphorylation for the detection of clopidogrel resistance in patients with ischemic cardiovascular diseases.. J Thromb Haemost 2005; 3: 85-92.
    CrossrefPubMedGoogle Scholar
  • 22 Schwarz UR. et al. Flow cytometry analysis of intracellular VASP phosphorylation for the assessment of activating and inhibitory signal transduction pathways in human platelets-definition and detection of ticlopidine/ clopidogrel effects.. Thromb Haemost 1999; 82: 1145-1152.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 23 Rao AK. 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.
    CrossrefPubMedGoogle Scholar
  • 24 Samara WM. et al. The difference between clopidogrel responsiveness and posttreatment platelet reactivity.. Thromb Res 2005; 115: 89-94.
    CrossrefPubMedGoogle Scholar
  • 25 Angiolillo DJ. et al. Randomized Comparison of a High Clopidogrel Maintenance Dose in Patients With Diabetes Mellitus and Coronary Artery Disease Results of the Optimizing Antiplatelet Therapy in Diabetes Mellitus (OPTIMUS) Study.. Circulation 2007; 115: 708-716.
    CrossrefPubMedGoogle Scholar
  • 26 Kastrati 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.
    CrossrefPubMedGoogle Scholar
  • 27 Gurbel PA. et al. The relation of dosing to clopidogrel responsiveness and the incidence of high posttreatment platelet aggregation in patients undergoing coronary stenting.. J Am Coll Cardiol 2005; 45: 1392-1396.
    CrossrefPubMedGoogle Scholar
  • 28 Gurbel PA. 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.
    CrossrefPubMedGoogle Scholar
  • 29 Angiolillo DJ. et al. High clopidogrel loading dose during coronary stenting: effects on drug response and interindividual variability.. Eur Heart J 2004; 25: 1903-1910.
    CrossrefPubMedGoogle Scholar
  • 30 von Beckerath N. 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.
    PubMedGoogle Scholar
  • 31 Montalescot G. Assessment of the best loading dose of clopidogrel to blunt platelet activation, inflammation, and ongoing necrosis (ALBION) Study.. EuroPCR Paris France 2005; 23: 23.
    PubMedGoogle Scholar
  • 32 Patti G. 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.
    CrossrefPubMedGoogle Scholar
  • 33 Cuisset T. 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; 48: 1339-1345.
    CrossrefPubMedGoogle Scholar
  • 34 Kastrati A. 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.
    CrossrefPubMedGoogle Scholar
  • 35 Jernberg T. et al. Prasugrel achieves greater inhibition of platelet agregation and a lower rate of non-responders compared with clopidogrel in aspirintreated patients with stable coronary artery disease.. Eur Heart J 2006; 27: 1166-1173.
    CrossrefPubMedGoogle Scholar
  • 36 Storey RF. et al. Inhibition of ADP-induced P-selectin expression and platelet leukocyte conjugate formation by clopidogrel and the P2Y12 receptor antagonist AR-C69931MX but not aspirin.. Thromb Haemost 2002; 88: 488-494.
    Article in Thieme ConnectPubMedGoogle Scholar