High postclopidogrel platelet reactivity in non-ST-elevation acute coronary syndrome treated with stenting: a clue for adverse prognosis?

Abstract

Patients presenting to the hospital with an acute coronary syndrome without ST-segment elevation (NSTE-ACS) are characterized by a common underlying pathophysiological mechanism represented by the rupture or erosion of an atherosclerotic coronary plaque with differing degrees of superimposed thrombosis and distal embolization [1]. They are, however, a heterogeneous group, ranging from low to high risk, partly because the tendency to the progression of coronary thrombosis to total coronary occlusion is highly variable. The Clinical Guidelines of both the European Society of Cardiology (ESC) [2] and the American College of Cardiology/ American Heart Association (ACC/AHA) [3] have identified the importance of early risk stratification for patients with NSTE-ACS for selecting the intensity of antiplatelet therapy and the need of early revascularization, frequently represented by percutaneous coronary intervention (PCI). For patients in whom the diagnosis is in doubt, only aspirin is suggested; for those in whom the diagnosis is confirmed based on the electrocardiographic or biochemical criteria, the addition of clopidogrel is encouraged. Finally, in the presence of high-risk features, the use of a platelet GP IIB/IIIA inhibitor is recommended followed by an early revascularization. These recommendations are based on the assumption that the extent and magnitude of platelet activation are causally linked to an adverse prognosis [4], particularly at the short term, and that the suppression of platelet reactivity should be pursued in order to minimize the occurrence of thrombotic events before, during, and after PCI [5]. In this issue of the Journal of Thrombosis and Haemostasis, Cuisset et al. [6] report on the prognostic importance of low platelet response to dual antiplatelet therapy in patients with NSTE-ACS. They studied 106 patients admitted within 12 h after the last chest pain episode, undergoing PCI with stenting within 48 h after admission. All patients received standard dose clopidogrel on top of aspirin and, at the time of PCI, tirofiban were administered at discretion of the interventional cardiologist (25% of patients). A single blood sample was obtained just before PCI and analyzed by platelet aggregometry using both ADP (10 lmol L) and arachidonic acid (0.5 mg mL) as agonists to explore the responses to clopidogrel and aspirin, respectively. Twelve recurrent cardiovascular events (11.3%) occurred during 30 day follow-up. They consisted of 10 hospitalizations for recurrent ACS (one sub-acute stent thrombosis), one stroke and one death. Patients were divided into quartiles according to the ADP or arachidonic acidinduced maximal intensity of platelet aggregation. Patients of the highest quartile (Quartile 4) were defined as low responders . The authors found that the clinical outcome was significantly associated with platelet response to clopidogrel [Quartile 4 vs. 1,2,3: OR (95%CI) 22.4 (4.6–109)] and, to a lower extent, to aspirin [Quartile 4 vs. 1,2,3: OR (95%CI): 5.76 (1.54–35.61)]. The authors conclude that a platelet aggregation test performed just before PCI identifies low responders to dual antiplatelet therapy with an increased risk of recurrent cardiovascular events. A possible explanation for these findings is the presence, in patients with NSTE-ACS, of a high-baseline platelet reactivity and thrombotic burden, which may contribute to a lower clopidogrel antiplatelet effect particularly during the first days of treatment [7]. Accordingly, a 450 mg clopidogrel loading dose given ‡3 h before PCI resulted in a lower inhibition of platelet aggregation in patients with a higher unstable angina class on presentation when compared with patients having stable angina or lower unstable angina class [8]. The results of the study of Cuisset et al. [6] are noteworthy as, for the first time, they show that, among patients with NSTEACS treated with both aspirin and clopidogrel and undergoing Correspondence: Marcello Galvani, Fondazione Cardiologica Sacco, P.zza F.lli Ruffini, 6, 47100 Forli, Italy. Tel.: +39 0543 33263; fax. +39 0543 735115; e-mail: galvanim@tin.it Journal of Thrombosis and Haemostasis, 4: 536–538