Variability in responsiveness to clopidogrel in patients with intermittent claudication

Abstract

Objective: The concept of clopidogrel resistance is frequently evoked in the cardiac literature. The variability of antiplatelet response in patients with intermittent claudication has not been investigated. The aim of this study was to describe the effect of the addition of clopidogrel to aspirin using ex vivo measures of platelet activation in patients with life-style limiting intermittent claudication.

Design of study: Data from randomised controlled trial.

Materials: Data from 67 patients with intermittent claudication taking part in a randomised controlled trial and who received clopidogrel in addition to aspirin was analysed.

Methods: Platelet activation was measured using whole-blood flow cytometric measurement of ADP-stimulated fibrinogen binding at baseline and 12h after administration of a loading dose of 300 mg clopidogrel. Patients continued to receive 75 mg clopidogrel daily for 30 days and platelet activation was again measured at day 30. Compliance with treatment was assessed by counting returned tablets.

Results: Six patients were excluded from analysis because of incomplete compliance with treatment. Six of the sixty-one patients (9.8%) showed no reduction in platelet activation 12h after administration of the loading dose of clopidogrel. At 30 days these six patients still showed no response to clopidogrel. Amongst the remaining 55 patients, the mean reduction in fibrinogen binding after clopidogrel administration was 51.5% (95% CI: 43.8-59.2). Amongst responders there was a wide variability in reduction of fibrinogen binding in response to clopidogrel (range 8.11-97.7%). Four of these patients (6.6%) showed a reduction of more than 95% in fibrinogen binding.

Conclusions: Patients with intermittent claudication show a wide variability in their response to clopidogrel. While a small proportion of these patients shows no response at all, another small group appears to respond excessively to clopidogrel. Clinical studies are required to identify whether hyper-responders are at increased risk of bleeding complications and whether hyporesponders are at a higher risk of thrombotic events.