Background Clopidogrel has provided a significant reduction in major vascular events in patients with peripheral artery disease in general, and those undergoing percutaneous transluminal balloon angioplasty in particular. At present, it is not possible to predict which patients will require re-stenosis, amputation, thrombosis or reoperation of the lower limb following percutaneous transluminal balloon angioplasty. However, different polymorphisms have been associated with differences in clopidogrel response in acute coronary syndrome patients.

Purpose The aim was to study the association of theses genetic variations with the clopidogrel response in a cohort of Spanish patients with peripheral artery disease and perform a meta-analysis combining these data with other data published previously.

Material and methods 72 patients with lower limb atherosclerotic disease following percutaneous transluminal balloon angioplasty and treated with clopidogrel were recruited. We evaluated the combined effect of ABCB1 3435 C >T genotype, CYP2C19*2 and CYP2C19*3 genotypes and rates of the primary efficacy endpoint, including atherothrombotic ischaemic events, diagnosed by ultrasound imaging, 6 and/or 12 months after prescription of clopidogrel. Reoperation for lower limb thrombosis post-PTA and amputation were also recorded. Other clinical parameters used to evaluate the clinical evolution of the patients were: intermittent claudication, toe brachial pressure index, arterial PVR test and Fontaine/Routherford degree, measured 6 and/or 12 months after initiation of therapy with clopidogrel.

Results Subjects carrying at least one CYP2C19*2 allele and/or ABCB1 TT had a significantly higher risk for the primary endpoint (OR=5.0, 95% CI 1.75 to 14.27, p = 0.003) than non-carrier patients. LOF carrier patients were associated with a worse Fontaine/Routherford degree than non-LOF patients (p < 0.0001, OR=13.96 (4.44–43.8). The meta-analysis confirmed the association analysis of CYP2C19*2 polymorphism with new atherothrombotic ischaemic events (OR=5.40, 95% CI 2.30 to 12.70).

Conclusion Our results support the role of the CYP2C19 and ABCB1 polymorphisms as a genetic marker of cardiovascular events in atherosclerosis of the arteries of patients with lower limb disease following PTA treated with clopidogrel.

No conflict of interest.