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 Original Research Article

Objectives We 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). Background High 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. Methods A 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. Results The 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). Conclusions In NSTE ACS patients undergoing coronary stenting, a 600-mg loading dose of clopidogrel shows its benefit on platelet reactivity and clinical prognosis.