In 2013, the CHANCE study, led by the National Center for Clinical Research in Neurological Diseases, was published in the New England Journal of Medicine (NEJM) [1]. The CHANCE study found that co-administration of clopidogrel with aspirin within 24 hours of symptom onset reduced the risk of subsequent stroke by 32.0% and did not increase the risk of bleeding compared with aspirin alone. The CHANCE protocol has rewritten antithrombotic guidelines for secondary stroke prevention in many countries and regions.

 

 

The latest findings published in the New England Journal of Medicine

 

Through the CHANCE study, it was found that patients with CYP2C19 loss-of-function gene had poor efficacy on the CHANCE study program (clopidogrel combined with aspirin therapy). ). On December 30, 2021, the CHANCE-2 research topped NEJM again [2]. The results of the CHANCE-2 study showed that for patients with minor ischemic stroke and transient ischemic attack who carry an inactive CYP2C19 allele, ticagrelor combined with aspirin is more effective than clopidogrel combined with aspirin in preventing stroke recurrence. The former had a 23% lower rate of stroke recurrence within 90 days than the latter; there was no difference in the risk of severe or moderate bleeding between the two groups, but the total number of bleeding events in the ticagrelor group exceeded that in the clopidogrel group. This research pioneered the gene-guided precision medicine treatment in the field of antiplatelet. About 60% of Asians carry the above inactivation loci, so the results have important value for secondary stroke prevention in Asian populations.

                    

 

The CHANCE-2 study is a randomized, double-blind, placebo-controlled trial conducted at 202 research centers in China, which enrolled patients with minor ischemic stroke or transient ischemic attack (TIA) who had CYP2C19 inactivation allele patients. Patients were randomized 1:1 within 24 hours of onset to receive ticagrelor and clopidogrel placebo, or clopidogrel and ticagrelor placebo; in addition Both groups received 21-day aspirin therapy. The primary endpoint was new ischemic or hemorrhagic stroke within 90 days. A total of 11,255 patients were screened, 6412 patients were enrolled, and 191 patients (6.0%) in the ticagrelor group and 243 patients (7.6%) in the clopidogrel group experienced stroke within 90 days. (hazard ratio, 0.77; 95% confidence interval, 0.64-0.94; P=0.008)

 

 

The safety endpoint of the CHANCE-2 study showed that intracranial hemorrhage occurred in 3 patients (0.1%) in the ticagrelor-aspirin group and 6 patients (0.2%) in the clopidogrel-aspirin group. Fatal bleeding occurred in 3 patients (0.1%) in each group. The incidence of bleeding was 5.3% in the ticagrelor-aspirin group compared with 2.5% in the clopidogrel-aspirin group, and the overall risk of bleeding was higher in the ticagrelor group than in the clopidogrel group. Adverse events occurred in 540 patients (16.8%) in the ticagrelor-aspirin group compared with 427 patients (13.3%) in the clopidogrel-aspirin group.

The "CYP2C19 Genotype and Clopidogrel Treatment CPIC Guidelines" updated by the Clinical Pharmacogenomics Implementation Consortium (CPIC) in 2022 provides new evidence for neurovascular diseases mainly from the CHANCE-2 study in my country. In terms of neurovascular diseases, based on the different genotypes of CYP2C19, the CPIC guidelines propose corresponding antiplatelet therapy recommendations. Therefore, timely detection of CYP2C19 genotype in the early stage of the treatment process of neurovascular diseases (including the treatment of acute ischemic stroke or TIA, secondary prevention of stroke or prevention of thromboembolic events after neurointerventional surgery) can effectively guide the Medication regimen for patients with neurovascular disease to reduce neurovascular risk.

 

 

 

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references:

[1]NEnglJMed2013；369:11-19DOI:10.1056/NEJMoa1215340

[2]NEnglJMed2021;385:2520-2530DOI:10.1056/NEJMoa2111749