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Genetic Polymorphisms and Clopidogrel Efficacy for Acute Ischemic Stroke or Transient Ischemic Attack: A Systematic
Yuesong Pan1, Weiqi Chen1, Yun Xu1
1From Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, China (Y.P., W.C., X.Z., L.L., Q.Z., G.W., Yongjun Wang, Yilong Wang); China National Clinical Research Center for Neurological Diseases, Beijing (Y.P., W.C., X.Z., L.L., Q.Z., G.W., Yongjun Wang, Yilong Wang); Center of Stroke, Beijing Institute for Brain Disorders, China (Y.P., W.C., L.H., X.Z., L.L., Q.Z., G.W., Yongjun Wang, Yilong Wang); Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, China (Y.P., W.C., L.H., X.Z., L.L., Q.Z., G.W., Yongjun Wang, Yilong Wang); Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, Beijing, China (Y.P.); Beijing Municipal Key Laboratory of Clinical Epidemiology, China (Y.P.); Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, China (Y.X.); Department of Neurology, The People's Hospital of Deyang City, China (X.Y.); Department of Neurology, Changhai Hospital, Second Military Medical University, Shanghai, China (Y.H.); Department of Neurology, Xinqiao Hospital, the Third Military Medical University, Chongqing, China (Q.Y.); Department of Neurology, the Second Hospital of Tianjin Medical University, China (X.L.); The First Affiliated Hospital, Jinan University, Guangzhou, China (L.H.); and Dell Medical School, University of Texas at Austin, TX (S.C.J.).
Insights
Patients with ischemic stroke or TIA carrying CYP2C19 loss-of-function alleles face higher risks of stroke and vascular events when treated with clopidogrel. This genetic factor impacts clopidogrel efficacy, highlighting the need for personalized treatment strategies.
Area of Science:
- Pharmacogenomics
- Neurology
- Cardiovascular Medicine
Background:
- The efficacy of clopidogrel in patients with ischemic stroke or transient ischemic attack (TIA) is influenced by genetic variations, but findings remain inconsistent.
- CYP2C19 genotype is a key genetic factor investigated for its impact on clopidogrel response.
Purpose of the Study:
- To conduct a systematic review and meta-analysis assessing the association between genetic polymorphisms, particularly CYP2C19 genotype, and clopidogrel efficacy in stroke or TIA patients.
- To evaluate the risk of clinical events, including stroke, composite vascular events, and bleeding, based on genetic profiles.
Main Methods:
- A comprehensive literature search was performed on PubMed and EMBASE up to June 24, 2016.
- Included studies focused on clopidogrel-treated patients with stroke or TIA and reported genetic polymorphism data.
- Primary endpoints were stroke, composite vascular events, and bleeding events.
Main Results:
- Analysis of 15 studies involving 4762 patients revealed that carriers of CYP2C19 loss-of-function alleles (*2, *3, *8) had a significantly increased risk of stroke (12.0% vs 5.8%; RR, 1.92; P<0.001).
- Composite vascular events were also more frequent in these carriers (13.7% vs 9.4%; RR, 1.51; P=0.01), while bleeding rates did not differ significantly (2.4% vs 3.1%; RR, 0.89; P=0.59).
- No significant heterogeneity was found for stroke risk, but it was present for composite vascular events. Other genetic variants showed limited associations, except for PON1, P2Y12, and COX-1 in one study.
Conclusions:
- Patients with ischemic stroke or TIA who carry CYP2C19 loss-of-function alleles are at a higher risk of experiencing stroke and composite vascular events when treated with clopidogrel.
- These findings underscore the importance of CYP2C19 genotype in predicting clopidogrel response and guiding therapeutic decisions in this patient population.
Background:
The association of genetic polymorphisms and clopidogrel efficacy in patients with ischemic stroke or transient ischemic attack (TIA) remains controversial. We performed a systematic review and meta-analysis to assess the association between genetic polymorphisms, especially CYP2C19 genotype, and clopidogrel efficacy for ischemic stroke or TIA.
Methods:
We conducted a comprehensive search of PubMed and EMBASE from their inceptions to June 24, 2016. Studies that reported clopidogrel-treated patients with stroke or TIA and with information on genetic polymorphisms were included. The end points were stroke, composite vascular events, and any bleeding.
Results:
Among 15 studies of 4762 patients with stroke or TIA treated with clopidogrel, carriers of CYP2C19 loss-of-function alleles (*2, *3, and *8) were at increased risk of stroke in comparison with noncarriers (12.0% versus 5.8%; risk ratio, 1.92, 95% confidence interval, 1.57-2.35; P<0.001). Composite vascular events were also more frequent in carriers of CYP2C19 loss-of-function alleles than in noncarriers (13.7% versus 9.4%; risk ratio, 1.51, 95% confidence interval, 1.10-2.06; P=0.01), whereas bleeding rates were similar (2.4% versus 3.1%; risk ratio, 0.89, 95% confidence interval, 0.58-1.35; P=0.59). There was no evidence of statistical heterogeneity among the included studies for stroke, but there was for composite vascular events. Genetic variants other than CYP2C19 were not associated with clinical outcomes, with the exception that significant associations of PON1, P2Y12, and COX-1 with outcomes were observed in 1 study.
Conclusions:
Carriers of CYP2C19 loss-of-function alleles are at greater risk of stroke and composite vascular events than noncarriers among patients with ischemic stroke or TIA treated with clopidogrel.
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