Background Clopidogrel is a prodrug metabolised by the isoenzyme CYP2C19 to its active form. The antiplatelet response is affected by genetic polymorphisms, with CYP2C19*2 being the most important, with the highest level of evidence associated with a poor prognosis in the treatment of peripheral arterial disease (PAD). Other factors also determine the evolution of PAD patients undergoing percutaneous transluminal angioplasty (PTA). The condition of the patient at discharged, use of stents and number of operated vessels may also affect the prognosis.
Purpose Our purpose was to compare the influence of these surgical variables and the baseline condition of patients with the influence of the polymorphism CYP2C19*2 in response to clopidogrel in patients undergoing PTA.
Material and methods This was a retrospective observational study including patients undergoing PTA treated with clopidogrel and discharged from our hospital between 2010 and 2013. Variables included: Fontaine Scale at discharge, pulse–volume recordings (PVR), ankle–brachial index, claudication distance, number of treated regions, and presence of stent and balloon with or without drugs. Endpoint for effectiveness was occurrence of cardiovascular events (thrombosis, myocardial infarction, stroke, re-intervention or cardiovascular death). The polymorphism was determined from saliva samples and test of allelic discrimination (Taqman). The influence of the variables studied on the response was expressed as odds ratio (statistically relevant) and p value. Data were collected from patients’ medical records.
Results 72 patients undergoing PTA between 2010 and 2013 were recruited. Average age was 67.4±9.4 years and 16 (22.2%) were women. 18 patients (25%) were carriers of CYP2C19*2 and none of the CYP2C19*3 polymorphism. 25 patients (34.7%) had a cardiovascular event and 11 patients (15.2%) were carriers of the CYP2C19*2 polymorphism. We did not find a statistically relevant association between clopidogrel response, measured as the appearance of a cardiovascular event, and any of the variables (Fontaine Scale p=0.11, PVR p=0.11, claudication distance p=0.26, ITB p=0.49, balloon with drugs p=0.17, stent p=0.11, number of treated regions p=0.92). However, we found an important relationship between the response and the presence of the CYP2C19*2 polymorphism (OR 4.49 (1.45–13.84), p=0.009).
Conclusion The presence of the CYP2C19*2 polymorphism seems to be a better predictor of antiplatelet response to clopidogrel in patients undergoing PTA than any quantifying surgical variable or baseline condition of the patient.
No conflict of interest
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