It was the aim of this study to compare the efficacy of early platelet inhibition by 600 mg clopidogrel and acetylsalicylic acid (ASA) to a triple therapy including a glycoprotein IIb-IIIa receptor blocker. Immediate percutaneous coronary intervention (PCI) is recommended for high-risk acute coronary syndromes. In this setting the efficacy of platelet inhibition is unknown. One hundred patients were randomized to receive ASA and 600 mg clopidogrel, or additional open-label tirofiban (bolus of 10 µg/kg body weight followed by continued infusion of 0.15 µg/kg body weight per minute) as soon as non-ST - segment elevation myocardial infarction was diagnosed. The primary endpoint was the reduction of infarct size determined by post-interventional increases of cardiac troponin T (cTnT). Secondary endpoints included platelet function measured by optical and impedance aggregometry using ADP (5 and 20 µM) and collagen (1 µg/ml) as platelet agonists. Tirofiban maximized platelet inhibition (p<0.0001) immediately and was associated with significantly lower post-interventional cTnT concentrations (p=0.0352). In the dual platelet inhibition arm, clopidogrel was not effective in 69% of patients at the time of coronary intervention, and still in 47%, if pre-treatment time was >120 minutes. The frequency of cardiovascular (death, myocardial infarction, revascularization) and bleeding events was comparable. Platelet aggregation is not adequately inhibited in cTnT - positive patients in the setting of immediate PCI with very short pre-treatment times. Only tirofiban provided consistent and effective inhibition of platelet aggregation at the time of immediate or very early invasive therapy.
1
Silber S,
Albertsson P,
Aviles FF.
et al. Guidelines for percutaneous coronary interventions. The Task Force for Percutaneous Coronary Interventions of the European Society of Cardiology. Eur Heart J 2005; 26: 804-847.
2
Bertrand ME,
Simoons ML,
Fox KA.
et al. Management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J 2002; 23: 1809-1840.
3
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.
4
Gurbel PA,
Bliden KP,
Hiatt BL.
et al. Clopidogrel for coronary stenting: response variability, drug resistance, and the effect of pretreatment platelet reactivity. Circulation 2003; 107: 2908-29013.
5
Gurbel PA,
Cummings CC,
Bell CR.
et al. Onset and extent of platelet inhibition by clopidogrel loading in patients undergoing elective coronary stenting: the Plavix Reduction Of New Thrombus Occurrence (PRONTO) trial. Am Heart J 2003; 145: 239-247.
6
Muller I,
Seyfarth M,
Rudiger S.
et al. Effect of a high loading dose of clopidogrel on platelet function in patients undergoing coronary stent placement. Heart 2001; 85: 92-93.
7
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.
8
Steen H,
Giannitsis E,
Futterer S.
et al. Cardiac troponin T at 96 hours after acute myocardial infarction correlates with infarct size and cardiac function. J Am Coll Cardiol 2006; 48: 2192-2194.
9
Ivandic BT,
Giannitsis E,
Schlick P.
et al. Determination of aspirin responsiveness by use of whole blood platelet aggregometry. Clin Chem 2007; 53: 614-619.
10
Ivandic BT,
Schlick P,
Staritz P.
et al. Determination of clopidogrel resistance by whole blood platelet aggregometry and inhibitors of the P2Y12 receptor. Clin Chem 2006; 52: 383-388.
11
Steinhubl SR,
Berger PB,
Brennan DM.
et al. Optimal timing for the initiation of pre-treatment with 300 mg clopidogrel before percutaneous coronary intervention. J Am Coll Cardiol 2006; 47: 939-943.
12
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.
13
Frossard M,
Fuchs I,
Leitner JM.
et al. Platelet function predicts myocardial damage in patients with acute myocardial infarction. Circulation 2004; 110: 1392-1397.
14
Sibbing D,
Beckerath von O,
Schomig A.
et al. Platelet function in clopidogrel-treated patients with acute coronary syndrome. Blood Coagul Fibrinolysis 2007; 18: 335-339.
15
Giannitsis E,
Steen H,
Kurz K.
et al. Cardiac magnetic resonance imaging study for quantification of infarct size comparing directly serial versus single time-point measurements of cardiac troponin T. J Am Coll Cardiol 2008; 51: 307-314.
16
Steinhubl SR.
Assessing the optimal level of platelet inhibition with GPIIb/IIIa inhibitors in patients undergoing coronary intervention. Rationale and design of the GOLD study. J Thromb Thrombolysis 2000; 09: 199-205.