Benefit of a 600-mg Loading Dose of Clopidogrel on Platelet Reactivity and Clinical Outcomes in Patients With Non–ST-Segment Elevation Acute Coronary Syndrome Undergoing Coronary Stenting

ObjectivesWe analyzed the benefit of a 600-mg clopidogrel loading dose on platelet reactivity and clinical outcomes after stenting for non–ST-segment elevation acute coronary syndrome (NSTE ACS).BackgroundHigh post-treatment platelet reactivity (HPPR = adenosine diphosphate 10 μmol·l−1[ADP]–induced platelet aggregation >70%) is a marker for low responders to dual antiplatelet therapy with increased risk of recurrent cardiovascular (CV) events after stenting for NSTE ACS.MethodsA total of 292 consecutive NSTE ACS patients undergoing coronary stenting were included and randomly received a 300-mg (n = 146) or 600-mg (n = 146) loading dose of clopidogrel at least 12 h before percutaneous coronary intervention. A single post-treatment blood sample was obtained before percutaneous coronary intervention to analyze maximal intensity of ADP-induced platelet aggregation and platelet surface expression of P-selectin. One-month follow-up CV events were recorded.ResultsThe ADP-induced platelet aggregation and expression of P-selectin were significantly lower in patients receiving 600 mg than in those receiving 300 mg (mean ± SD: 50 ± 19% vs. 61± 16%, p < 0.0001 and 0.38 ± 0.24 arbitrary units vs. 0.60 ± 0.40 arbitrary units; p < 0.0001 respectively). Persistence of HPPR was less common in patients receiving 600 mg than in those receiving 300 mg (15 vs. 25%, p = 0.03). During the 1-month follow-up, 18 CV events (12%) occurred in the 300-mg group versus 7 (5%) in the 600-mg group (p = 0.02); this difference was not affected by adjustment for conventional CV risk factors (p = 0.035).ConclusionsIn NSTE ACS patients undergoing coronary stenting, a 600-mg loading dose of clopidogrel shows its benefit on platelet reactivity and clinical prognosis