Does poor clopidogrel response increase ischemic complications in patients undergoing noncoronary endovascular interventions?
Poor clopidogrel responders, identified by genotyping or platelet function testing, have significantly higher odds of ischemic complications after noncoronary endovascular interventions compared to normal responders.
OBJECTIVE: Short- or long-term periprocedural clopidogrel, with or without aspirin, is standard of care after several endovascular interventions. However, clopidogrel fails to prevent platelet aggregation in 15% to 50% of the population due to mutations in the CYP2C19 gene. Two methodologies, CYP2C19 genotyping and platelet function testing (PFT), predict clopidogrel response, but their utility in preventing complications after endovascular interventions is underappreciated. This meta-analysis (1) characterizes current literature on genotyping and PFT as means of identifying clopidogrel response and (2) evaluates the impact of abnormal clopidogrel response on postprocedural ischemic complications (stent thrombosis, restenosis, reintervention, amputation, revascularization, transient ischemic attack/stroke, or myocardial infarction) and bleeding complications. METHODS: We conducted a systematic review and meta-analysis of papers reporting CYP2C19 genotyping or PFT to assess clopidogrel response in patients undergoing noncoronary endovascular interventions. A total of 272 papers were screened. After excluding 263 papers, nine articles remained. We described the distribution of poor responders obtained using genotyping and PFT. We compared the odds of developing ischemic complications in poor vs normal clopidogrel responders. We compared the odds of developing bleeding complications in hyper-responders vs normal clopidogrel responders. RESULTS: Four papers assessing clopidogrel response by genotyping and three by PFT reported on ischemic complications. The mean prevalence of poor response was 43.2% ± 10.1% by genotyping and 23.2% ± 8.9% by PFT. All patients received postprocedural clopidogrel. Cumulative ischemic complication rates were 35.1% for poor responders and 14.0% for normal responders. Higher odds of ischemic complications were observed in poor clopidogrel responders identified by genotyping (odds ratio OR: 2.8, 95% confidence interval CI: 2.1-3.8, P < .001) or by PFT (OR: 6.3, 95% CI: 2.0-20.0, P = .02). Three papers assessed bleeding complications in patients undergoing neuroendovascular interventions. There was no difference in the odds of major bleeding events between hyper-responders and normal responders (OR: 6.2, 95% CI: 0.6-61.7, P = .12). The low number of papers precluded a formal comparison of effectiveness of genotyping vs PFT in predicting complications. CONCLUSIONS: Among patients receiving clopidogrel after endovascular interventions, poor responders experience ischemic complications more frequently. Genotyping chips and PFT assay kits are commercially available and effectively detect poor clopidogrel responders. Genotyping has the advantage of detection before clopidogrel initiation. Rigorous studies are needed to establish the preferred testing modality and to determine whether test result-driven modification of antiplatelet therapy reduces periprocedural complications.
Zhang et al. (Mon,) studied this question.