Associations between P2RY12 gene polymorphisms and risks of clopidogrel resistance and adverse cardiovascular events after PCI in patients with acute coronary syndrome

Abstract

Clopidogrel resistance in patients with acute coronary syndrome (ACS) is one of the key causes of recurrent cardiovascular disease (CVD) events after percutaneous coronary intervention (PCI). Clopidogrel targets the platelet membrane receptor P2RY12 to inhibit platelet aggregation via adenosine diphosphate (ADP). This study aimed to investigate the relationships between P2RY12 polymorphisms and the risk of clopidogrel resistance and adverse CVD events after PCI. From January 2015 to December 2014, patients who had been diagnosed with ACS undergoing PCI and treated with clopidogrel were recruited for this prospective cohort study (N = 498). Data regarding demographics, medication intake, and ACS lesion were recorded, and whole blood samples were collected for biochemical tests, ADP-induced platelet aggregation ratio detection, and P2RY12 genotyping. P2RY12 genotyping was performed by polymerase chain reaction. The left ventricular ejection fraction was calculated by echocardiography. After 3 to 12 months of follow-up, data regarding any adverse CVD event or death were recorded. The allele frequencies for the T variation alleles in C34T and G52T of P2RY12 were 20.3% and 11.6%, respectively. Patients with T variations at C34T or G52T of P2RY12 had a significantly higher risk of clopidogrel resistance (C34T: P < 0.001; G52T: P = 0.003) and total cardiovascular events (C34T: P = 0.013; G52T: P = 0.018) compared to those with the wild-type genotype. Moreover, multivariable logistic regression showed that patients with the T variations in C34T (odds ratio [OR]: 2.89 (95% confidence interval [CI]: 1.48-5.64), P = 0.002) and G52T (OR: 3.68 [95% CI: 1.71-7.92], P = 0.001) also had a significantly higher risk of clopidogrel resistance. Also, the T variations in C34T (OR: 2.68 [95% CI: 1.07-6.73], P = 0.035) and G52T (OR: 5.64 [95% CI: 1.52-20.88], P = 0.010) significantly increased the risk of post-PCI CVD events after accounting for confounding factors. The P2RY12 gene polymorphisms C34T and G52T were significantly associated with a higher risk of clopidogrel resistance and sequential cardiovascular events in Chinese ACS patients after PCI.Abbreviations: ACS = acute coronary syndrome, ADP = adenosine diphosphate, CAD = coronary artery disease, CI = confidence interval, CVD = cardiovascular disease, CYP = cytochrome P450, LVEF = left ventricular ejection fraction, OR = odds ratio, PAR = platelet aggregation ratio, PCI = percutaneous coronary intervention, PCR = polymerase chain reaction, STEMI = ST segment elevated myocardial infarction.

P2Y12 Polymorphisms and the Risk of Adverse Clinical Events in Patients Treated with Clopidogrel: A Meta-Analysis

“…Many studies investigated the relationship of the P2Y12 gene polymorphism and adverse clinical events, but these studies [8,9,[22][23][24][25][26][27][28][29][30][31][32][33][34] had divergent results. It is therefore necessary to perform a meta-analysis exploring this association.…”

“…Then, six studies [14][15][16][17][18] with incomplete data, one study [19] with incorrect data, one study [20] with a followup < 3 months and one study [21] without full-text were excluded respectively. Fifteen studies [8,9,[22][23][24][25][26][27][28][29][30][31][32][33][34] met the inclusion criteria. However, one study [26] was not included, because the genotypes of all recruited population were of homozygous wild-type (GG).…”

Effect of Dialysis on Antiplatelet Drug Efficacy in Uremic Patients with Coronary Heart Disease

“…There is a similar mechanism for clopidogrel, which functions as an ADP receptor antagonist that can selectively inhibit the binding of ADP to the platelet receptor. [ 13 ] Activation of the ADP and glycoprotein GPIIb/IIIa complex is thus prevented, resulting in irreversible inhibition of platelet aggregation. Partially removing clopidogrel does not change this scenario.…”

Tirofiban hydrochloride sodium chloride injection combined with cardiovascular intervention in the treatment of Acute Myocardial Infarction

“…As study has shown that the occurrence of cardiovascular events after PCI is closely related to platelets. 14 Although PCI can effectively recanalize the coronary artery, sometimes myocardial reperfusion is not successful; therefore, ant platelet therapy is not only the key to the treatment of ST-segment elevation myocardial infarction, but also an important part of preventing cardiovascular events during and after PCI. Tirofiban hydrochloride is a kind of the third generation of platelet membrane receptor antagonist, which is highly efficient and irreversibly in inhibiting platelet adhesion and aggregation.…”