Modified clopidogrel loading dose according to platelet reactivity monitoring in patients carrying ABCB1 variant alleles in patients with clopidogrel resistance.

Abstract

OBJECTIVES: The aim of the present study was to investigate the impact of a adjusted clopidogrel loading dose (LD) according to platelet reactivity index in carriers of ABCB1 mutant allele undergoing percutaneous coronary intervention (PCI). METHODS: All patients met the inclusion criteria were recruited in the present study. Platelet reactivity was measured using the vasodilator-stimulated phosphoprotein (VASP) index. High treatment platelet reactivity (HTPR) was determined by a cut-off value of >50%. The genetic polymorphism of ABCB1 was determined by allele-specific polymerase chain reaction (PCR). In patients carrying ABCB1 and HTPR after a first 300-mg LD of clopidogrel, dose adjustment was performed by using up to 3 additional 300-mg LDs to obtain a VASP index<50%. The rate of major adverse cardiovascular events (MACE) and major or minor bleeding in one month were recorded. RESULTS: 536 patients were included in the present study. One hundred seventy-two patients (32%) carried ABCB1 mutant allele (11 homozygotes [2%] and 161 heterozygotes [30%]). The VASP index in these patients was significantly higher than in homozygotic patients for the wild allele (65.5±13.8% vs. 47.6±21.8%; p<0.001). Of the 172 ABCB1 mutant allele carriers, 130 were considered to have HTPR. After a second clopidogrel LD, the VASP index was significantly decreased in these patients (66.9±12.8% vs.50.2±18.3%; <0.001). Finally, dose adjustment according to platelet reactivity monitoring enabled 88% of ABCB1 mutant allele carriers and 91% of wild allele carriers exhibiting HTPR to reach a VASP index<50%. The rate of MACE and major or minor bleeding in one-month follow-up between the wild allele carriers and the mutant allele carriers didn't differentiate significantly. CONCLUSIONS: Increased and adjusted clopidogrel loading dose according to platelet reactivity monitoring attenuated clopidogrel resistance in carriers of ABCB1 mutant allele.