Pan Y, et al. - Researchers examined the link between ABCB1 polymorphisms and clopidogrel efficacy for minor stroke or transient ischemic attack (TIA). They found reduced efficacy of clopidogrel plus aspirin treatment in association with ABCB1 polymorphism, compared with aspirin, among patients with minor ischemic stroke or TIA. Considering the genetic polymorphism of ABCB1 was recommended when prescribing clopidogrel for these patients.

Methods

• This was a prespecified secondary analysis of the Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events (CHANCE) randomized clinical trial.
• Participants were included from October 1, 2009, to July 30, 2012 and comprised 3010 patients with minor stroke or TIA at 73 sites in China with experience in conducting genetic studies.
• The analysis was performed on March 20, 2018.
• Among 2836 patients treated with clopidogrel plus aspirin (n = 1414) or aspirin alone (n = 1422), genotyping of 4 single-nucleotide polymorphisms (ABCB1 –154T>C [rs4148727], ABCB1 3435C>T [rs1045642], CYP2C19*2 [681G>A, rs4244285], and CYP2C19*3[636G>A, rs4986893]) was performed.
• In the context of CYP2C19 status, another gene associated with clopidogrel efficacy, they assessed the association of ABCB1 genetic variants (–154 TC/CC and 3435 CT/TT) with clopidogrel efficacy.
• Clopidogrel combined with aspirin or aspirin alone was administered to the patients in the CHANCE trial, using randomization.
• Assessments were carried out for primary efficacy outcome ie, stroke recurrence after 3 months and for safety outcome ie, any bleeding risk after 3 months.

Results

• Overall, 2836 patients with median age of 61.8 years (interquartile range, 54.4-71.1 years) were analyzed,1887 patients (66.5%) were male.
• They noted 2146 (75.7%) patients were carriers of ABCB1 –154 TC/CC (570 [20.1%]) or 3435 CT/TT (1851 [65.3%]) genotype.
• Patients with ABCB1 –154 TT and 3435 CC genotype (hazard ratio [HR], 0.43; 95% CI, 0.26-0.71) but not those with ABCB1 –154 TC/CC or 3435 CT/TT genotype (HR, 0.78; 95% CI, 0.60-1.03) demonstrated a reduced risk of new stroke in association with clopidogrel plus aspirin treatment vs aspirin (P = .04 for interaction).
• Findings revealed a combined association of ABCB1 and CYP2C19 polymorphisms with new stroke.
• There was no association between the risk of bleeding for clopidogrel plus aspirin treatment and ABCB1genotypes (2.3% and 1.3% vs 1.9% and 2.2%; P = .25 for interaction in patients with or without ABCB1 –154 TC/CC or 3435 CT/TT genotype).