Clinical and pharmacological parameters determine relapse during clopidogrel treatment of acute coronary syndrome

The therapeutic efficacy of clopidogrel as an anti-platelet drug varies among individuals, being the mainstream hypothesis that its bioavailability depends on the individual genetic background and/or interactions with other drugs.

A total of 477 patients receiving double anti-aggregation therapy with aspirin and clopidogrel, after suffering a first event, were followed for 1 year to record relapse, as a surrogate end point to measure their therapeutic response, as defined by presenting with an acute coronary event (unstable angina, STEMI, or NSTEMI), stent thrombosis/restenosis or cardiac mortality. Anthropometric, clinical and pharmacological variables along with CYP2C19 genotypes were analyzed for their association with the disease relapse phenotype.

Only 75 patients (15%) suffered a relapse, which occurred during the first six months of therapy, with a peak at 4.5 months. An initial univariate analysis identified that patients in the relapse group were significantly older (67.4 ± 11.0 vs 61.6 ± 12.3 years old) and presented with diffuse coronary disease, insulin-dependent type 2 diabetes mellitus dyslipidemia, and arterial hypertension. A poor clinical response to the platelet anti-aggregation regime also occurred more frequently among patients taking, along with aspirin and clopidogrel, acenocoumarol and Calcium Channel Blockers, while no association was found according to CYP2C19 genotypes. A retrospective multivariate analysis indicated that patients belonging to the non-responder phenotype to treatment with aspirin and clopidogrel were older, presented with diffuse coronary disease, a group largely overlapping with type 2 insulin-dependent diabetes mellitus, and were taking dihidropyrimidinic calcium channel blockers.

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