Stroke: Minor stroke, the more chronic diseases, the worse the treatment effect

Minor stroke (MS) and transient ischemic attack (TIA) often indicate a high risk of subsequent stroke, and account for a large proportion of cerebrovascular diseases in China
.
CHANCE trial (clopidogrel in the treatment of patients at high risk of acute non-disabling cerebrovascular events) 2 and POINT trial (platelet-directed inhibition of new TIA and mild ischemic stroke) in the Chinese population, using clopidogrel and aspirin in combination Dual antiplatelet therapy (DAPT) has been shown to significantly reduce the risk of early new strokes in patients with MS or TIA

Clopidogrel is an original drug that needs to be metabolized before inhibiting ADP-induced platelet aggregation
.
However, the response to clopidogrel varies greatly among individuals

Studies have shown that the efficacy of clopidogrel-aspirin therapy in reducing the risk of recurrent stroke depends on the carrying status of the cytochrome P4502C19 (CYP2C19) loss-of-function allele in the Chinese population
.
On the contrary, a recent POINT sub-study found that the CYP2C19 loss-of-function carrier status and the results of the treatment group did not significantly interact

The failure to confirm the results of the CHANCE test may be because the CYP2C19 genotype can only explain part of the pharmacodynamic response to clopidogrel, and some clinical factors such as obesity and insulin resistance also have a promoting effect
.

Angiolillo et al.
recently reported a simple tool for identifying patients with high platelet reactivity (HPR) taking clopidogrel who are at increased risk of adverse ischemic events
.

Age, BMI, Chronic Kidney Disease, Diabetes and Genotyping (ABCDGENE) is a validated scale that contains 5 independent HPR predictors: 4 clinical factors (age>75 years old, body mass index>30 kg/ m2, chronic kidney disease [glomerular filtration rate <60 mL/minute] and diabetes) and 1 genetic factor (CYP2C19 allele)
.
On the basis of the cutoff value ≥10, the ABCD-GENE score significantly distinguishes the high-risk and low-risk patients of the event in the external clinical validation cohort (FAST-MI data set) of patients with myocardial infarction

Using the data from the CHANCE trial, Liye Dai et al.
of Tiantan Hospital used the ABCD-GENE score to study the appropriate value of MS or TIA patients
.

In the post-analysis of the CHANCE trial (clopidogrel treatment of patients at high risk of acute non-disabling cerebrovascular events), they calculated ABCD-GENE scores for all patients who participated in the study

In a total of 2923 patients with mild stroke/transient ischemic attack, 2273 (77.
76%) had an ABCD-GENE score of <10, and 650 (22.
24%) had an ABCD-GENE score of ≥10
.

Compared with aspirin alone, in patients with ABCD-GENE score <10 and ABCD-GENE score ≥10, the risk ratios (95% CIs) of clopidogrel-aspirin therapy for stroke recurrence were 0.
70 (0.
54-0.
91), respectively And 0.
76 (0.
46-1.
24)
.

Based on the ABCD-GENE scores 0 to 5, 6 to 24 and >24 for stratified analysis, the risk ratio of clopidogrel-aspirin therapy for stroke recurrence was 0.
57 (95% CI, 0.
38-0.
85), 0.
78 (0.
58-1.
06) And 1.
20 (0.
44-3.
28) (P value of trend = 0.
0052)
.

The important significance of this study lies in the discovery that among the Chinese population of minor stroke/transient ischemic attack, patients with higher ABCD-GENE scores have decreased efficacy of clopidogrel-aspirin treatment
.
The study showed that CYP2C19 genotype and clinical risk factors can be used to comprehensively estimate the efficacy of clopidogrel-aspirin treatment through the ABCD-GENE score

Original Source:
Dai L, Xu J, Yan H, et al.
Application of Age, Body Mass Index, Chronic Kidney Disease, Diabetes, and Genotyping Score for Efficacy of Clopidogrel: Secondary Analysis of the CHANCE Published Trial.
  Stroke.