To guide the prevention of stroke recurrence in the Chinese population, and Wang Yongjun's team from Tiantan Hospital reached the top of NEJM

▎For WuXi AppTec content team editors, stroke (commonly known as stroke) is one of the most important causes of death and disability globally and in China
.

The latest "China Cardiovascular Health and Disease Report" data shows that there are 13 million people suffering from stroke (stroke)
.

The Global Burden of Disease Working Group estimates that the lifetime risk of stroke in the Chinese population is as high as 39.
3%, which means that about 2 out of every 5 Chinese people will suffer a stroke in their lifetime
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October 29, 2021 is the 16th "World Stroke Day"
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On the eve of this year’s “World Stroke Day”, Professor Wang Yongjun’s team from Beijing Tiantan Hospital, Capital Medical University announced the main results of the CHANCE-2 study at the 2021 World Stroke Conference (WSC).
The research paper was simultaneously published in the New England Journal of Medicine ( NEJM), which provides important guidance for the prevention of stroke recurrence in the Chinese population
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The CHANCE-2 study was conducted in 202 centers in China and a total of 6,412 patients were enrolled
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The results show that for patients with acute mild ischemic stroke or transient ischemic attack (TIA), if they carry the CYP2C19 inactivating allele, ticagrelor combined with aspirin is more effective than clopidogrel combined with aspirin in preventing stroke recurrence
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Nearly 60% of the Chinese population carries the CYP2C19 inactivating allele
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Screenshot source: The New England Journal of Medicine.
Among patients with acute mild ischemic stroke or transient ischemic attack, the risk of re-stroke within 3 months after the first stroke is about 5%-10%, preventing recurrence (ie two Level prevention) is very important
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The CHANCE-2 study led by Professor Wang Yongjun compared two secondary prevention treatment strategies
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Carrying the CYP2C19 inactivated allele, which is better between ticagrelor and clopidogrel? For patients with acute mild ischemic stroke or transient ischemic attack, the dual antiplatelet therapy of clopidogrel combined with aspirin has been shown to be more effective than aspirin alone in reducing subsequent recurrence events
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However, clopidogrel needs to be transformed by hepatic cytochrome p450 (CYP) to be active.
Therefore, in people who carry the CYP2C19 inactivated allele, clopidogrel is less effective in secondary prevention
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There are significant differences in the proportion of this inactivated allele in different ethnic groups, about 25% and 60% in white patients and Asian patients, respectively
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The antiplatelet effect of ticagrelor does not require metabolic activation.
Compared with clopidogrel, its inhibition of platelet aggregation may be similar or higher
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In patients with acute mild to moderate ischemic stroke or high-risk transient ischemic attack, the secondary prevention effect of ticagrelor combined with aspirin has also been proven to be better than aspirin alone
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The results of the previous PRINCE trial suggested that ticagrelor combined with aspirin may have more obvious antiplatelet effects than clopidogrel combined with aspirin in people carrying CYP2C19 alleles, but large studies are still needed to verify this
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Chinese population research results: Ticagrelor dual-drug regimen has a lower risk of recurrence.
In order to answer the above questions, Professor Wang Yongjun led the CHANCE-2 study
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This is a randomized, double-blind, placebo-controlled trial.
After screening more than 10,000 patients in 202 centers in China, 6412 patients with mild ischemic stroke or transient cerebral ischemia carrying the CYP2C19 inactivated allele were finally included.
Patients with seizures
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The median age of the patients was 64.
8 years, 33.
8% were women, and 98.
0% were Han nationality
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Patients received ticagrelor (180 mg on day 1, 90 mg twice a day on days 2-90) or clopidogrel (300 mg on day 1, and 2-90) in 1:1 groups within 24 hours after the onset of stroke symptoms.
75 mg once a day for 90 days).
In addition, both groups took aspirin for 21 days
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The main efficacy outcome was a new stroke event within 90 days, and the main safety outcome was a moderate to severe bleeding event within 90 days
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The results showed that 191 patients (6.
0%) in the ticagrelor group and 243 patients (7.
6%) in the clopidogrel group had a stroke within 90 days, and the risk of recurrence in the ticagrelor group was significantly reduced by 23% (HR 0.
77; 95%) CI, 0.
64-0.
94; P=0.
008)
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A number of secondary outcome indicators also showed better efficacy of ticagrelor combined with aspirin, including new stroke events within 30 days, vascular events within 90 days (stroke, transient ischemic attack, myocardial infarction or death from vascular causes), ischemia stroke, disabling stroke, stroke severity
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▲The cumulative incidence of stroke in the two groups of patients with ticagrelor combined with aspirin (blue line) and clopidogrel combined with aspirin (red line)
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(Image source: Reference [1]) In terms of safety, overall, there were more bleeding events in the ticagrelor group, but it was mainly due to mild bleeding.
There was no difference in the risk of moderate to severe bleeding between the two treatment groups
.

There were 170 patients (5.
3%) and 80 patients (2.
5%) in the ticagrelor group and clopidogrel group, respectively, with any bleeding events, 9 patients (0.
3%) and 11 patients (0.
3%), respectively Severe or moderate bleeding occurred
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Reference significance to clinical practice The discussion section of the paper pointed out that for stroke patients with CYP2C19 inactivated alleles, ticagrelor can be used as a clinical alternative to antiplatelet drugs.
These patients may not respond well to clopidogrel, especially This is because of the high burden of stroke recurrence and the high carrying rate of CYP2C19 inactivated alleles in East Asian populations
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The cumulative risk curve for stroke is different in the first week or later, and then similar, which indicates that among CYP2C19 inactivated allele carriers, the benefit of ticagrelor over clopidogrel is mainly reflected in the first stroke.
The near stage
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However, the research team also stated that the clinical utility of current genomics-guided antiplatelet drug treatment options may be limited by the availability of genetic testing technologies and tools, and the cost-effectiveness of genotype-guided medication strategies needs further study
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