2-oxo-clopidogrel and Myocardial-Infarction

One of the most common polymorphisms of ABCB1 gene, a synonymous mutation C3435T (rs1045642), is associated with increased in vivo activity. The main goal of this study was to determine the association of C3435T polymorphism with clopidogrel and 2-oxo-clopidogrel concentrations in plasma.. The patients were recruited upon acute myocardial infarction diagnosis. They were all tested for ABCB1 C3435T polymorphism. In plasma, drawn 1 h after the drug administration, concentrations of clopidogrel and 2-oxo-clopidogrel were measured using UHPLC-DAD-MS analysis.. Due to differences in the maintenance doses, we have calculated the dose-adjusted concentrations of clopidogrel (0.2 ng/ml/mg (0.1-0.4)) and 2-oxo-clopidogrel (2.1 ng/ml/mg (0.5-4.6)). Patients carrying at least one C allele achieved significantly higher serum concentration of clopidogrel (p < 0.001), as well as dose-adjusted clopidogrel (p < 0.001) and 2-oxo-clopidogrel concentrations (p < 0.05).. The ABCB1 3435CC genotype is associated with increased clopidogrel and 2-oxo-clopidogrel dose-adjusted concentrations. Therefore, the ABCB1 C3435T genotyping should be one of the parameters taken into account when deciding about the dosing regimen of clopidogrel.

Topics: Adult; Aged; Aged, 80 and over; ATP Binding Cassette Transporter, Subfamily B; Clopidogrel; Cross-Sectional Studies; Female; Genotype; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Polymorphism, Genetic; Ticlopidine

To observe the relationship between ATP-binding cassette subfamily B member 1 (ABCB1) and cytochrome P450 (CYP)2C19 polymorphisms and the effect of clopidogrel post percutaneous coronary intervention in patients with coronary artery disease.. A total of 300 consecutive patients with acute coronary syndrome undergoing selected percutaneous coronary intervention in General Hospital of the People's Liberation Army from October 2010 to August 2012 and treated with clopidogrel were enrolled and retrospectively analyzed. Antiplatelet responsiveness of clopidogrel was estimated by thrombelastograph. The patients were divided into 3 groups: remarkable efficacy group (adenosine diphosphate pathway inhibition rate >80%, 105 cases), effective group (adenosine diphosphate pathway inhibition rate of 50%-80%, 100 cases), and poor responsiveness group (adenosine diphosphate pathway inhibition rate <50%, 95 cases). CYP2C19 and ABCB1 polymorphisms were detected by PCR combined with restrictive fragment length polymorphism (PCR-RELP) method in all patients. A total of 200 patients were performed by high performance liquid chromatography with electrospray tandem mass spectrum methods (HTLC-MS/MS), which was applied for determining the plasma concentration level of clopidogrel metabolites between remarkable efficacy group and poor responsiveness group. Major adverse cardiovascular events and bleeding events were observed through follow-up.. (1) There were significantly differences in gender, smoking and alanine transaminase level among 3 groups(P<0.01 or 0.05). (2)There was no significant difference in the ratio of TT, CC and CT genotype of ABCB1 gene among 3 groups(P>0.05). There was significant difference in the ratio of poor, middle and strong metabolizer genotype of CYP2C19 gene (P<0.05). (3)Recurrent angina rates were 8.6%(9/105), 6.0%(6/100) and 18.9%(18/95) (P<0.05), and bleeding events rates were 1.0% (1/105), 1.0%(1/100) and 8.4%(8/95)respectively (P<0.01) in remarkable efficacy group, effective group and poor responsiveness group during the 1 year follow up. There were no significant difference in rates of myocardial infarction, heart failure, ischemic stroke and death among 3 groups (all P>0.05) during follow up. Rates of major adverse cardiovascular events and bleeding events were similar in patients with TT, CC and CT genotype of ABCB1 (14.6%(13/89), 12.8(19/148)and 11.6%(5/43), P>0.05). Rates of major adverse cardiovascular events and bleeding events were 9.5%(2/21), 17.8(27/152) and 7.5%(8/107) in poor, middle and strong metabolizer genotype of CYP2C19 gene patients (P<0.05). (4) Plasma concentration of clopidogrel was significantly lower and relative concentration of acid metabolites was significantly higher in poor responsiveness group than in remarkable efficacy group(P<0.01 or 0.05). There was no significantly different in plasma relative concentration of 2-oxo-clopidogrel between remarkable efficacy group and poor responsiveness group.. ABCB1 gene polymorphism is not but CYP2C19 gene polymorphisms is related with antiplatelet responsiveness of clopidogrel and clinical cardiovascular disease events in patients with acute coronary syndrome undergoing selected percutaneous coronary intervention.

Topics: Acute Coronary Syndrome; Alleles; Angina Pectoris; ATP Binding Cassette Transporter, Subfamily B; Clopidogrel; Coronary Artery Disease; Cytochrome P-450 CYP2C19; Genotype; Hemorrhage; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Polymorphism, Genetic; Tandem Mass Spectrometry; Ticlopidine