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.

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 mumol x 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.