Abstract
Objectives: We sought to study the genetic polymorphisms of ABCB1 gene in post percutaneous coronary intervention (PCI) patients with clopidogrel resistance. Background: Dual antiplatelet therapy (DAPT) is a guideline mandated therapy for patients who undergo PCI. However there exists interindividual variability in drug response to the antiplatelet agents leading to recurrent thrombotic events. Genetic polymorphisms of ABCB1 gene are one among the causes of this interindividual variability. Methods: It is a single center prospective trial and includes221 patients who underwent PCI and were given clopidogrel as a part of DAPT. Platelet reactivity was assessed by grading of platelet activity index (PAI) and considered as high on treatment platelet reactivity (HTPR), i.e., clopidogrel resistance if PAI > 5. Genetic analysis for ABCB1 C-T polymorphism was done by polymerase chain reaction (PCR) and single strand confirmation polymorphism (SSCP) analysis. Results: Amongst 221 patients, 37 (16.7%) patients had ABCB1 C-T polymorphisms. The mean PAI value in these patients was 5.1 ± 3.0, while it was 3.5 ± 2.5 in those patients without ABCB1 C-T polymorphisms (p = 0.004). Compared to patients without HTPR, the occurrence of primary endpoints was not significantly increased in patients with HTPR except for stent thrombosis which was significantly high in patients with HTPR. HTPR was also associated with ABCB1 C-T polymorphisms (p = 0.04), but these polymorphisms did not predict the clinical outcome. Conclusions: There was significant prevalence of ABCB1 C-T polymorphisms in patients with HTPR. However it was not an independent risk factor for clopidogrel resistance and also it did not influence adverse cardiovascular outcomes.
Highlights
A 4-fold rise in the prevalence of coronary heart disease (CHD) is seen in India during the past 40 years and the current prevalence is estimated to be between 7% and 13% in urban [1] [2] [3] and between 2% and 7% in rural [4] [5] populations
Platelet reactivity was assessed by grading of platelet activity index (PAI) and considered as high on treatment platelet reactivity (HTPR), i.e., clopidogrel resistance if PAI > 5
Dramatic expansion in the use of percutaneous coronary intervention (PCI) is seen in the past three decades and PCI has evolved from plain old balloon angioplasty (POBA) to implantation of bare metal stent (BMS) to drug eluting stent (DES) and currently to the use of biovascular scaffolds
Summary
A 4-fold rise in the prevalence of coronary heart disease (CHD) is seen in India during the past 40 years and the current prevalence is estimated to be between 7% and 13% in urban [1] [2] [3] and between 2% and 7% in rural [4] [5] populations. Dramatic expansion in the use of PCI is seen in the past three decades and PCI has evolved from plain old balloon angioplasty (POBA) to implantation of bare metal stent (BMS) to drug eluting stent (DES) and currently to the use of biovascular scaffolds. Despite this guide line directed regimen stent thrombosis (ST) remained a significant complication resulting in recurrent ischemic events. This ST may be attributed to many factors and drug nonresponsiveness contributes to it. The ABCB1 gene encodes multi drug resistance protein 1 (MDR1), which is an ATP dependent efflux transporter, responsible for the transport of a portion of drug (clopidogrel) back into the lumen thereby reducing the bioavailability. Influence of ABCB1 C-T genetic polymorphisms on clopidogrel nonresponsiveness is still controversial
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