​Ticagrelor opens a new pattern of stroke dual-antibody therapy

*Only for reference by medical professionals.
On October 28th, the world's top authoritative journal "New England Journal of Medicine (NEJM)" published the full text of the CHANCE-2 study [1] initiated by Professor Wang Yongjun from Tiantan Hospital
.

Studies have confirmed that in patients with mild ischemic stroke or transient ischemic attack (TIA) carrying the loss-of-function allele of CYP2C19, compared with clopidogrel combined with aspirin treatment, ticagrelor combined with aspirin treatment takes 3 months The risk of recurrence of internal stroke was reduced by 23%
.

This study consolidates the dominant position of ticagrelor in antiplatelet therapy for patients with non-disabling ischemic cerebrovascular disease, and brings more effective and safe new treatment measures to these patients
.

1 Research interpretation: CHANCE-2 is the first prospective, multi-center, double-blind, randomized controlled phase III clinical study based on CYP2C19 genotyping in the field of cerebrovascular disease in the world so far
.

To compare the efficacy of ticagrelor combined with aspirin antiplatelet therapy and clopidogrel combined with aspirin antiplatelet therapy in patients with mild ischemic stroke or TIA carrying CYP2C19 loss of function Compared with clopidogrel, whether ticagrelor can further improve the efficacy and safety of antiplatelet in patients with stroke or TIA, it can provide diagnosis and treatment evidence for precise and individualized antiplatelet therapy
.

The study enrolled 6412 patients with mild ischemic stroke (NIHSS score ≤ 3) or high-risk TIA (ABCD2 score ≥ 4) within 24 hours of onset in 202 centers across the country and carrying CYP2C19 functional loss alleles
.

Patients were randomly divided into experimental groups: ticagrelor (loading dose 180 mg; 90 mg, bid maintenance) combined with aspirin (loading dose 100-300 mg; 100 mg/d maintenance) for 21 days, followed by ticagrelor as a single agent Treatment to 90 days; control group: clopidogrel (loading dose 300 mg; 75 mg/d maintenance) combined with aspirin (dose same as before) for 21 days, followed by clopidogrel monotherapy for 90 days
.

The primary efficacy endpoint is any new stroke event (ischemic or hemorrhagic stroke) within 90 days
.

The primary safety endpoint was severe or moderate bleeding as defined by GUSTO
.

The CHANCE-2 study showed that the stroke recurrence rate in the ticagrelor combined with aspirin treatment group was 6.
0% (191/3205) at 90 days, which was significantly lower than that in the clopidogrel combined aspirin treatment group with 7.
6% (243/3207) (HR 0.
77, 95%CI: 0.
64-0.
94, P=0.
008, Figure 1)
.

In terms of safety, ticagrelor combined with aspirin compared with clopidogrel combined with aspirin group, the incidence of severe or moderate bleeding (0.
3% vs 0.
3%, HR 0.
82, 95%CI: 0.
34-1.
98), intracranial hemorrhage events The incidence (0.
1% vs 0.
2%, HR 0.
49, 95%CI: 0.
12-1.
96) was not significantly different
.

Figure 12 Outlook: 2016 JAMA magazine published the CHANCE study gene subgroup analysis showed that clopidogrel combined with aspirin antiplatelet therapy group has no therapeutic advantage in patients with CYP2C19 loss-of-function allele compared with aspirin monotherapy group [2]
.

The mutation rate of CYP2C19 gene in China is as high as 58.
8%[2], and its impact on the efficacy of clopidogrel is far greater than that of Western populations.
Therefore, screening suitable populations according to genotyping and accurately formulating effective antiplatelet treatment plans is a major clinical issue that urgently needs to be resolved.
Problem
.

The CHANCE-2 study published this time provides new evidence for antiplatelet therapy in patients with mild ischemic stroke or TIA
.

Ticagrelor is a new type of P2Y12 receptor antagonist and a non-prodrug
.

This means that the two major advantages are that it takes effect directly after absorption, and the antithrombotic effect can be achieved earlier in the acute treatment
.

Secondly, it is not affected by metabolic enzymes, and the population has the same antiplatelet reactivity, reducing the risk of gene resistance
.

The previous THALES[3] study has confirmed that ticagrelor combined with aspirin can significantly reduce the recurrence of stroke or death in patients with mild ischemic stroke or TIA 30 days later (HR 0.
83 95% CI 0.
71-0.
96).
In terms of safety, ticagrelor has a higher risk of serious bleeding events, but the risks do not exceed the benefits
.

Therefore, we have good reasons to use this treatment in people with mild ischemic stroke or TIA
.

The results of CHANCE-2 study confirmed that in patients with mild ischemic stroke or TIA who carry the CYP2C19 loss-of-function gene, ticagrelor-based antiplatelet therapy will have a better clinical efficacy than standardized treatment strategies that follow existing guidelines
.

To provide more solid evidence-based medical evidence for the use of ticagrelor in the secondary prevention of cerebrovascular diseases
.

According to reports, according to the research results of CHANCE-2, China can reduce the recurrence of about 30,000 stroke patients every year.
If the direct hospitalization cost of each patient is about 35,000 yuan, it can save China about 1 billion yuan in medical expenses every year.

.

 References: [1].
Wang, Y.
, et al.
, Ticagrelor versus Clopidogrel in CYP2C19 Loss-of-Function Carriers with Stroke or TIA.
2021.
[2].
Wang, Y.
, et al.
, Association Between CYP2C19 Loss-of-Function Allele Status and Efficacy of Clopidogrel for Risk Reduction Among Patients With Minor Stroke or Transient Ischemic Attack.
Jama, 2016.
316(1): p.
70-8.
[3].
Johnston, SC, et al.
, Ticagrelor and Aspirin or Aspirin Alone in Acute Ischemic Stroke or TIA.
N Engl J Med, 2020.
383(3): p.
207-217.
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