Consistent Platelet Inhibition During Long-Term Maintenance Clopidogrel Therapy Among Three Hundred Fifty-Nine Compliant Outpatients with Documented Vascular Disease

Abstract

Conclusion: Long-term therapy with clopidogrel provides more consistent platelet inhibition than that observed following initiation of therapy after acute vascular events. Summary: There have been conflicting reports on the effects of clopidogrel therapy on platelet inhibition after an acute vascular event. Some reports have documented a high incidence of clopidogrel nonresponsiveness, but these reports have been complicated by varying definitions and different platelet aggregation tests. This study sought to assess the effect of clopidogrel on platelet characteristics in outpatients who received maintenance dosages of clopidogrel (75 mg/d) for >30 days. This was a secondary analysis of presumably compliant patients treated with clopidogrel and aspirin. The patient cohort consisted of 237 who had undergone coronary artery stenting and 122 who had sustained an ischemic stroke. The mean duration of treatment was 5.8 months (range, 1-21 months). All patients exhibited inhibition of adenosine diphosphate-induced platelet activation (mean, 52.9%; range, 36%-70%) compared with preclopidogrel measurements. A diminished expression of platelet-endothelial cell adhesion molecule 1 (r = 0.75), glycoprotein 2B-3A (r = 0.62), and protease-activated receptor 1 (r = 0.71) were all correlated with inhibition of platelet aggregation. No patients were found to have platelet hyporesponsiveness or profound inhibition of platelet activity. Comment: The wide response variability to clopidogrel in the acute setting does not hold up with more long-term administration of the drug. The article suggests that problems related to clopidogrel resistance may be exaggerated by previous emphasis on short-term rather than long-term maintenance data.