Key result
CYP2C19 loss-of-function status is not significantly associated with recurrent stroke overall during DAPT.
Why the study?
Does CYP2C19 intermediate or poor metabolizer status increase the risk of recurrent stroke or major bleeding compared with extensive or ultrarapid metabolizer status in patients with small subcortical stroke treated with aspirin and clopidogrel dual antiplatelet therapy?
Cohort (n=522)
Double-blind
Yes
Does CYP2C19 intermediate or poor metabolizer status increase the risk of recurrent stroke or major bleeding compared with extensive or ultrarapid metabolizer status in patients with small subcortical stroke treated with aspirin and clopidogrel dual antiplatelet therapy?
CYP2C19 intermediate or poor metabolizer status was associated with higher odds of recurrent stroke in white patients receiving aspirin and clopidogrel after small subcortical stroke, but did not explain the excess major bleeding risk seen with dual antiplatelet therapy in the SPS3 trial.
Answers are grounded in this paper and cite their sources.
CYP2C19 status does not support risk stratification for recurrent stroke overall; leaves open race-specific effects in white patients.
BACKGROUND: The role of the CYP2C19 genotype on clopidogrel efficacy has been studied widely, with data suggesting reduced clopidogrel efficacy in loss-of-function variant carriers taking clopidogrel after percutaneous coronary intervention; however, data are limited regarding the association between CYP2C19 genetic variants and outcomes in stroke patients. We investigated whether CYP2C19 metabolizer status affects the risk of recurrent stroke or major bleeding in subcortical stroke patients taking dual antiplatelet therapy with aspirin and clopidogrel. METHODS AND RESULTS: CYP2C19*2 and CYP2C19*17 were genotyped in 522 patients treated with dual antiplatelet therapy from the Secondary Prevention of Small Subcortical Strokes (SPS3) study. CYP2C19 metabolizer status was inferred from genotype, and associations with the risk of recurrent stroke and major bleeding were assessed in the overall cohort and by race/ethnic group with logistic regression modeling. In the overall cohort, there were no differences in outcomes by CYP2C19 metabolizer status (recurrent stroke, odds ratio 1.81 [95% CI 0.76 to 4.30]; major bleeding, odds ratio 0.67 [95% CI 0.22 to 2.03]). In white participants, those with CYP2C19 intermediate or poor metabolizer status had higher odds of recurrent stroke (odds ratio 5.19 [95% CI 1.08 to 24.90]) than those with extensive or ultrarapid metabolizer status, but there was no evidence of difference in major bleeding. CONCLUSIONS: There were significant differences in recurrent stroke by CYP2C19 genotype-inferred metabolizer status in white subcortical stroke patients receiving dual antiplatelet therapy with aspirin and clopidogrel, consistent with cardiovascular studies on CYP2C19 and clopidogrel; however, the bleeding risk that led to early termination of the antiplatelet arm of the SPS3 trial does not appear to be explained by CYP2C19 genotype. This study was relatively underpowered; therefore, these findings should be interpreted with caution and warrant replication. CLINICAL TRIAL REGISTRATION: URL: www.clinicaltrials.gov. Unique identifier: NCT00059306.
No takes yet. Share an insight, caveat, or question.
McDonough et al. (2015) conducted a cohort in Small subcortical stroke or transient ischemic attack (n=522). CYP2C19 intermediate or poor metabolizer status (IM/PM) vs. CYP2C19 extensive or ultrarapid metabolizer status (EM/UM) was evaluated on Recurrent stroke (ischemic or hemorrhagic) (OR 1.81, 95% CI 0.76 to 4.30). CYP2C19 intermediate/poor metabolizer status was not associated with recurrent stroke overall, though risk was higher in white patients.
Synapse has enriched 10 related papers. Consider them for comparative context: