J Neurol Res

Journal of Neurology Research, ISSN 1923-2845 print, 1923-2853 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Neurol Res and Elmer Press Inc

Journal website https://jnr.elmerpub.com

Original Article

Volume 16, Number 2, June 2026, pages 88-98

Genotype-Guided Dual Antiplatelet Therapy in CYP2C19 Loss-of-Function Carriers With Stroke or Transient Ischemic Attack: A Meta-Analysis of Ticagrelor–Aspirin Versus Clopidogrel–Aspirin

↓ Figure 2. Risk of bias analysis. (a) Traffic-light plot of the risk of bias assessment using RoB 2, illustrating the bias risk results across each domain. (b) Overall risk of bias conclusion using RoB 2, summarizing the risk of bias.

↓ Figure 3. Analysis of primary efficacy outcome. The forest plot demonstrates that the administration of the ticagrelor–aspirin combination significantly reduced the incidence of recurrent stroke within 90 days compared to the clopidogrel–aspirin combination (RR, 0.72; 95% CI, 0.65–0.80; P < 0.00001). CI: confidence interval; RR: risk ratio.

↓ Figure 4. Analysis of secondary safety outcome. (a) The forest plot demonstrates that the administration of the ticagrelor–aspirin combination significantly reduced the incidence of composite vascular events compared to the clopidogrel–aspirin combination (RR, 0.74; 95% CI, 0.70–0.79; P < 0.00001). (b) The forest plot demonstrates that the administration of the ticagrelor–aspirin combination significantly reduced the incidence of intracranial hemorrhage compared to the clopidogrel–aspirin combination (RR, 0.50; 95% CI, 0.31–0.82; P = 0.005). (c) The forest plot demonstrates that the administration of the ticagrelor–aspirin combination significantly reduced the incidence of mortality compared to the clopidogrel–aspirin combination (RR, 0.53; 95% CI, 0.39–0.71; P < 0.0001). CI: confidence interval; RR: risk ratio.

↓ **Table 1.** Characteristics of Study Data
No.	Author	Sample size	Study design	Diagnosis	Intervention regimen	Control regimen
1.	Meng et al, 2024 [10]	6,412	The CHANCE-2 trial, a multicenter randomized double-blind trial	Transient ischemic attack who carried CYP2C19 loss-of-function alleles	Loading dose of 180 mg on day 1, followed by 90 mg twice daily for days 2–90	Loading dose of 75–300 mg on day 1, followed by 75 mg daily for 21 days	Loading dose of 300 mg, followed by 75 mg daily for days 2–90	Loading dose of 75–300 mg on day 1, followed by 75 mg daily for 21 days
2.	Wang et al, 2021 [9]	6,412	Randomized, doubled-blind trial	Transient ischemic attack who carried CYP2C19 loss-of-function alleles	Loading dose of 180 mg on day 1, followed by 90 mg twice daily for days 2–90	Loading dose of 75–300 mg on day 1, followed by 75 mg daily for 21 days	Loading dose of 300 mg, followed by 75 mg daily for days 2–90	Loading dose of 75–300 mg on day 1, followed by 75 mg daily for 21 days
3.	Wang et al, 2022 [11]	6,412	The CHANCE-2 trial, a multicenter randomized double-blind trial	Transient ischemic attack who carried CYP2C19 loss-of-function alleles	Loading dose of 180 mg on day 1, followed by 90 mg twice daily for days 2–90	Loading dose of 75–300 mg on day 1, followed by 75 mg daily for 21 days	Loading dose of 300 mg, followed by 75 mg daily for days 2–90	Loading dose of 75–300 mg on day 1, followed by 75 mg daily for 21 days
4.	Wang et al, 2022 [12]	6,412	The CHANCE-2 trial, a multicenter randomized double-blind trial	Transient ischemic attack who carried CYP2C19 loss-of-function alleles	Loading dose of 180 mg on day 1, followed by 90 mg twice daily for days 2–90	Loading dose of 75–300 mg on day 1, followed by 75 mg daily for 21 days	Loading dose of 300 mg, followed by 75 mg daily for days 2–90	Loading dose of 75–300 mg on day 1, followed by 75 mg daily for 21 days
5.	Wang et al, 2022 [13]	6,378	Post hoc analysis of a multicenter, randomized, double-blind, placebo-controlled trial	Transient ischemic attack who carried CYP2C19 loss-of-function alleles	Loading dose of 180 mg on day 1, followed by 90 mg twice daily for days 2–90	Loading dose of 75–300 mg on day 1, followed by 75 mg daily for 21 days	Loading dose of 300 mg, followed by 75 mg daily for days 2–90	Loading dose of 75–300 mg on day 1, followed by 75 mg daily for 21 days
6.	Wang et al, 2023 [14]	6,412	The CHANCE-2 trial, a multicenter randomized double-blind trial	Transient ischemic attack who carried CYP2C19 loss-of-function alleles	Loading dose of 180 mg on day 1, followed by 90 mg twice daily for days 2–90	Loading dose of 75–300 mg on day 1, followed by 75 mg daily for 21 days	Loading dose of 300 mg, followed by 75 mg daily for days 2–90	Loading dose of 75–300 mg on day 1, followed by 75 mg daily for 21 days
7.	Wang et al, 2023 [15]	6,412	The CHANCE-2 trial, a multicenter randomized double-blind trial	Transient ischemic attack who carried CYP2C19 loss-of-function alleles	Loading dose of 180 mg on day 1, followed by 90 mg twice daily for days 2–90	Loading dose of 75–300 mg on day 1, followed by 75 mg daily for 21 days	Loading dose of 300 mg, followed by 75 mg daily for days 2–90	Loading dose of 75–300 mg on day 1, followed by 75 mg daily for 21 days
8.	Wang et al, 2024 [16]	5,440	The CHANCE-2 trial, a multicenter randomized double-blind trial	Transient ischemic attack who carried CYP2C19 loss-of-function alleles	Loading dose of 180 mg on day 1, followed by 90 mg twice daily for days 2–90	Loading dose of 75–300 mg on day 1, followed by 75 mg daily for 21 days	Loading dose of 300 mg, followed by 75 mg daily for days 2–90	Loading dose of 75–300 mg on day 1, followed by 75 mg daily for 21 days
9.	Xie et al, 2023 [17]	6,412	The CHANCE-2 trial, a multicenter randomized double-blind trial	Transient ischemic attack who carried CYP2C19 loss-of-function alleles	Loading dose of 180 mg on day 1, followed by 90 mg twice daily for days 2–90	Loading dose of 75–300 mg on day 1, followed by 75 mg daily for 21 days	Loading dose of 300 mg, followed by 75 mg daily for days 2–90	Loading dose of 75–300 mg on day 1, followed by 75 mg daily for 21 days
10.	Yang et al, 2020 [7]	339	Pre-specified subgroup analysis of PRINCE trial	Transient ischemic attack who carried CYP2C19 loss-of-function alleles	Loading dose of 180 mg on day 1, followed by 90 mg twice daily for days 2–90	Loading dose of 300 mg on day 1, followed by 100 mg daily for 21 days	Loading dose of 300 mg, followed by 75 mg daily for days 2–90	Loading dose of 300 mg on day 1, followed by 100 mg daily for 21 days
11.	Yang et al, 2020 [8]	675	Pre-specified subgroup analysis of PRINCE trial	Transient ischemic attack who carried CYP2C19 loss-of-function alleles	Loading dose of 180 mg on day 1, followed by 90 mg twice daily for days 2–90	Loading dose of 300 mg on day 1, followed by 100 mg daily for 21 days	Loading dose of 300 mg, followed by 75 mg daily for days 2–90	Loading dose of 300 mg on day 1, followed by 100 mg daily for 21 days
12.	Zhang et al, 2023 [18]	6,412	The CHANCE-2 trial, a multicenter randomized double-blind trial	Transient ischemic attack who carried CYP2C19 loss-of-function alleles	Loading dose of 180 mg on day 1, followed by 90 mg twice daily for days 2–90	Loading dose of 75–300 mg on day 1, followed by 75 mg daily for 21 days	Loading dose of 300 mg, followed by 75 mg daily for days 2–90	Loading dose of 75–300 mg on day 1, followed by 75 mg daily for 21 days

↓ Table 1. Characteristics of Study Data

No.

Author

Sample size

Study design

Diagnosis

Intervention regimen

Control regimen

Ticagrelor

Aspirin

Clopidogrel

Aspirin

Meng et al, 2024 [10]

6,412

The CHANCE-2 trial, a multicenter randomized double-blind trial

Transient ischemic attack who carried CYP2C19 loss-of-function alleles

Loading dose of 180 mg on day 1, followed by 90 mg twice daily for days 2–90

Loading dose of 75–300 mg on day 1, followed by 75 mg daily for 21 days

Loading dose of 300 mg, followed by 75 mg daily for days 2–90

Loading dose of 75–300 mg on day 1, followed by 75 mg daily for 21 days

Wang et al, 2021 [9]

6,412

Randomized, doubled-blind trial

Transient ischemic attack who carried CYP2C19 loss-of-function alleles

Loading dose of 180 mg on day 1, followed by 90 mg twice daily for days 2–90

Loading dose of 75–300 mg on day 1, followed by 75 mg daily for 21 days

Loading dose of 300 mg, followed by 75 mg daily for days 2–90

Loading dose of 75–300 mg on day 1, followed by 75 mg daily for 21 days

Wang et al, 2022 [11]

6,412

The CHANCE-2 trial, a multicenter randomized double-blind trial

Transient ischemic attack who carried CYP2C19 loss-of-function alleles

Loading dose of 180 mg on day 1, followed by 90 mg twice daily for days 2–90

Loading dose of 75–300 mg on day 1, followed by 75 mg daily for 21 days

Loading dose of 300 mg, followed by 75 mg daily for days 2–90

Loading dose of 75–300 mg on day 1, followed by 75 mg daily for 21 days

Wang et al, 2022 [12]

6,412

The CHANCE-2 trial, a multicenter randomized double-blind trial

Transient ischemic attack who carried CYP2C19 loss-of-function alleles

Loading dose of 180 mg on day 1, followed by 90 mg twice daily for days 2–90

Loading dose of 75–300 mg on day 1, followed by 75 mg daily for 21 days

Loading dose of 300 mg, followed by 75 mg daily for days 2–90

Loading dose of 75–300 mg on day 1, followed by 75 mg daily for 21 days

Wang et al, 2022 [13]

6,378

Post hoc analysis of a multicenter, randomized, double-blind, placebo-controlled trial

Transient ischemic attack who carried CYP2C19 loss-of-function alleles

Loading dose of 180 mg on day 1, followed by 90 mg twice daily for days 2–90

Loading dose of 75–300 mg on day 1, followed by 75 mg daily for 21 days

Loading dose of 300 mg, followed by 75 mg daily for days 2–90

Loading dose of 75–300 mg on day 1, followed by 75 mg daily for 21 days

Wang et al, 2023 [14]

6,412

The CHANCE-2 trial, a multicenter randomized double-blind trial

Transient ischemic attack who carried CYP2C19 loss-of-function alleles

Loading dose of 180 mg on day 1, followed by 90 mg twice daily for days 2–90

Loading dose of 75–300 mg on day 1, followed by 75 mg daily for 21 days

Loading dose of 300 mg, followed by 75 mg daily for days 2–90

Loading dose of 75–300 mg on day 1, followed by 75 mg daily for 21 days

Wang et al, 2023 [15]

6,412

The CHANCE-2 trial, a multicenter randomized double-blind trial

Transient ischemic attack who carried CYP2C19 loss-of-function alleles

Loading dose of 180 mg on day 1, followed by 90 mg twice daily for days 2–90

Loading dose of 75–300 mg on day 1, followed by 75 mg daily for 21 days

Loading dose of 300 mg, followed by 75 mg daily for days 2–90

Loading dose of 75–300 mg on day 1, followed by 75 mg daily for 21 days

Wang et al, 2024 [16]

5,440

The CHANCE-2 trial, a multicenter randomized double-blind trial

Transient ischemic attack who carried CYP2C19 loss-of-function alleles

Loading dose of 180 mg on day 1, followed by 90 mg twice daily for days 2–90

Loading dose of 75–300 mg on day 1, followed by 75 mg daily for 21 days

Loading dose of 300 mg, followed by 75 mg daily for days 2–90

Loading dose of 75–300 mg on day 1, followed by 75 mg daily for 21 days

Xie et al, 2023 [17]

6,412

The CHANCE-2 trial, a multicenter randomized double-blind trial

Transient ischemic attack who carried CYP2C19 loss-of-function alleles

Loading dose of 180 mg on day 1, followed by 90 mg twice daily for days 2–90

Loading dose of 75–300 mg on day 1, followed by 75 mg daily for 21 days

Loading dose of 300 mg, followed by 75 mg daily for days 2–90

Loading dose of 75–300 mg on day 1, followed by 75 mg daily for 21 days

10.

Yang et al, 2020 [7]

339

Pre-specified subgroup analysis of PRINCE trial

Transient ischemic attack who carried CYP2C19 loss-of-function alleles

Loading dose of 180 mg on day 1, followed by 90 mg twice daily for days 2–90

Loading dose of 300 mg on day 1, followed by 100 mg daily for 21 days

Loading dose of 300 mg, followed by 75 mg daily for days 2–90

Loading dose of 300 mg on day 1, followed by 100 mg daily for 21 days

11.

Yang et al, 2020 [8]

675

Pre-specified subgroup analysis of PRINCE trial

Transient ischemic attack who carried CYP2C19 loss-of-function alleles

Loading dose of 180 mg on day 1, followed by 90 mg twice daily for days 2–90

Loading dose of 300 mg on day 1, followed by 100 mg daily for 21 days

Loading dose of 300 mg, followed by 75 mg daily for days 2–90

Loading dose of 300 mg on day 1, followed by 100 mg daily for 21 days

12.

Zhang et al, 2023 [18]

6,412

The CHANCE-2 trial, a multicenter randomized double-blind trial

Transient ischemic attack who carried CYP2C19 loss-of-function alleles

Loading dose of 180 mg on day 1, followed by 90 mg twice daily for days 2–90

Loading dose of 75–300 mg on day 1, followed by 75 mg daily for 21 days

Loading dose of 300 mg, followed by 75 mg daily for days 2–90

Loading dose of 75–300 mg on day 1, followed by 75 mg daily for 21 days