CYP2C19 Loss-of-Function Alleles and Clopidogrel Hyporesponsiveness in Patients with Reinfarction/Recurrent Myocardial Infarction after Coronary Stenting
Burabha Pussadhamma MD1, Chaiyasith Wongvipaporn MD1, Songsak Kiatchoosakun MD1, Suda Vannaprasaht MD2
Affiliation : 1 Department of Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand 2 Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
Background : CYP2C19 loss-of-function (LOF) alleles and clopidogrel hyporesponsiveness increased cardiovascular events
in patients with newly diagnosed myocardial infarction (MI). However, data of CYP2C19 genetic polymorphism and
clopidogrel hyporesponsiveness in patients with reinfarction/recurrent MI was lacked.
Objective : To investigate the prevalence and impact of CYP2C19 LOF alleles and clopidogrel hyporesponsiveness among
patients with reinfarction/recurrent MI after coronary stenting.
Materials and Methods : All consecutive patients who were taking clopidogrel and presented with reinfarction/recurrent MI
after coronary stenting at Queen Sirikit Heart Center of the Northeast and Srinagarind Hospital, Khon Kaen, Thailand, during
December 2012 to December 2015 were enrolled. Genotype analysis of CYP2C19 alleles were investigated, which CYP2C19*2
and *3 were defined as LOF alleles, and clopidogrel responsiveness was assessed by VerifyNow©P2Y12 assay (Accumetrics,
San Diego, CA, USA), which clopidogrel hyporesponsiveness was defined as P2Y12 reaction unit (PRU) >240. Survival data
of all patients were followed until December 2017.
Results : Sixty-seven patients were eligible, which mean age (SD) was 63 (10) years, 44 patients (65.7%) were male, and 27
patients (40.3%) presented with definite stent thrombosis (ST). Among overall patients, subgroup with definite ST, and
subgroup without ST, the number of patients (%) with CYP2C19 LOF alleles were 41(61.2%), 16 (59.3%), and 25(62.5%),
median PRU were 234, 260, and 215, number of patients (%) with clopidogrel hyporesponsiveness were 31(47.7%),
17(65.4%), and 14(35.9%), and five-year survival rate (95% confidence interval) were 67% (54-78%), 63% (42-78%), and
71% (53-83%), respectively. The presence of CYP2C19 LOF alleles was not associated with clopidogrel hyporesponsiveness
either in overall patients or in any subgroup. Survival analysis showed no effect of either CYP2C19 LOF alleles or
clopidogrel hyporesponsiveness on either short- or long-term mortality.
Conclusion : CYP2C19 LOF alleles and clopidogrel hyporesponsiveness is highly prevalent among Northeastern Thai
patients with reinfarction/recurrent MI, however, the clinical impact of both disorders was not evidenced. Hence, routine
platelet function testing and genetic testing in these particular patients may seems unnecessary.
Keywords : CYP2C19 loss-of-function allele, Clopidogrel hyporesponsiveness, Reinfarction, Recurrent myocardial infarction
