title: Modified clopidogrel loading dose according to platelet reactivity monitoring in patients carrying ABCB1 variant alleles in patients with clopidogrel resistance.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Cardiology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.
authors.forename: Xiao-dong
authors.initials: XD
authors.lastname: Wang
authors.forename: Dai-fu
authors.initials: DF
authors.lastname: Zhang
authors.forename: Xue-bo
authors.initials: XB
authors.lastname: Liu
authors.forename: Yan
authors.initials: Y
authors.lastname: Lai
authors.forename: Wei-gang
authors.initials: WG
authors.lastname: Qi
authors.forename: Yu
authors.initials: Y
authors.lastname: Luo
authors.forename: Bo
authors.initials: B
authors.lastname: Hu
authors.forename: Yi-an
authors.initials: YA
authors.lastname: Yao
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000368:Aged; D000483:Alleles; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology*; D000077144:Clopidogrel; D016903:Drug Monitoring; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D011446:Prospective Studies; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine