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PKP-003 Pharmacogenetics in antiplatelet treatment with clopidogrel in vascular pathology
  1. CL Dávila Fajardo1,
  2. X Díaz Villamarín1,
  3. F Fernandez2,
  4. LJ Martinez Gonzalez3,
  5. JG Sanchez Ramos4,
  6. S Martinez Huertas4,
  7. MDC Marin1,
  8. J Cabeza Barrera1
  1. 1San Cecilio University Hospital, Pharmacy, Granada, Spain
  2. 2San Cecilio University Hospital, Vascular Surgery, Granada, Spain
  3. 3Centro de Investigación Genyo, Genomic Dapartment, Granada, Spain
  4. 4San Cecilio University Hospital, Cardiology, Granada, Spain

Abstract

Background Clopidogrel is metabolised by CYP2C19 to the active metabolite responsible for the inhibition of platelet aggregation. The P-glycoprotein encoded by the ABCB1 gene is key in drug absorption. The effects differ according to genotype ABCB1 and CYP2C19. Intermediate and poor metabolizers and poor transporters (carriers of “loss of function” alleles: LOF) are responsible for the poor response to the antiplatelet drug.

This evidence has not yet been demonstrated in patients with peripheral vascular disease of the lower limbs undergoing percutaneous transluminal angioplasty.

Purpose To determine the occurrence of cardiovascular events (myocardial infarction, stroke, reoperation, PTA thrombosis, stent thrombosis, amputation and bypass) in patients undergoing PTA (+ - stent) for one year to monitor and study the association with the presence of genetic polymorphisms CYP2C19 and ABCB1. To determine the association between genetic polymorphisms and the Fontaine score (classification of ischemia).

Material and methods 45 lower limb disease patients with atherosclerosis of the arteries following PTA treated with clopidogrel were recruited. We evaluated the combined effect of ABCB1 3435 C > T genotype, CYP2C19*2 and CYP2C19*3 genotype and rates of the primary efficacy endpoint including ACS, stroke, reoperation for lower limb thrombosis post-PTA, stent thrombosis, bypass reconversion and amputation during 6 and/or 12 months after the prescription of clopidogrel, and other clinical parameters used to evaluate the clinical condition of the patients: intermittent claudication, toe-brachial pressure index (TBPI), arterial PVR test, Fontaine/Rutherford score measured at 6 and/or 12 months after the start of clopidogrel.

Results Subjects carrying at least one CYP2C19 reduced function allele and/or ABCB1 TT had a significantly higher risk of the primary endpoint (OR = 6.0, 95% CI 1.53–23.53, p = 0.010) than non-carriers patients. LOF patients were associated with a worse Fontaine/Rutherford score evolution than non-LOF patients (p < 0.0001, OR = 21.35 (3.85–118.35).

Conclusion CYP2C19 and ABCB1 polymorphisms could be used as genetic markers of cardiovascular events in vascular pathology.

References and/or acknowledgements No conflict of interest.

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