Double-blind randomized placebo-controlled trial of the antiplatelet effects of aspirin-clopidogrel combination versus aspirin alone at endovascular intervention for intermittent claudication of the lower limb

Abstract

Intermittent claudication is a common problem which causes significant impairment of quality of life and increased mortality. Endovascular recanalization, widely used for symptomatic relief, carries a high risk of reocclusion. Platelets play a central role in this process. Aspirin currently used in claudicants reduces the risk, and more potent antiplatelet strategies may reduce this further. The aim of this study was to investigate the antiplatelet effect of aspirin–clopidogrel versus aspirin alone in patients with claudication undergoing endovascular intervention. Methods: This was a double-blind randomized placebo-controlled trial; 132 patients were randomized to clopidogrel and aspirin or to placebo and aspirin with a loading dose 12 h before endovascular intervention. Flow cytometric measurement of platelet fibrinogen binding and P-selectin expression as measures of platelet activation status and of platelet responsiveness to stimulation at baseline, 12 h post-loading dose, 1 h, 24 h and 30 days postintervention. Results: Platelet activation was significantly diminished in the clopidogrel group at 12 h post-loading dose compared to baseline (P-selectin: 27·3 per cent reduction, P = 0·017; bound fibrinogen: 34·7 per cent reduction, P = 0·024; stimulated bound fibrinogen: 49 per cent, P < 0·001). No significant change was observed in the control group. Platelet function was significantly suppressed in the clopidogrel group at 1 h, 24 h and 30 days after endovascular intervention compared to the placebo group (P < 0·001). Conclusion: Clopidogrel–aspirin combination dramatically inhibits platelet function in claudicants before and after intervention. The combination treatment may help reduce reocclusion after endovascular recanalization.