Ticagrelor–Aspirin Versus Clopidogrel–Aspirin Among CYP2C19 Loss-of-Function Carriers With Minor Stroke or Transient Ischemic Attack in Relation to Renal Function: A Post Hoc Analysis of the CHANCE-2 Trial

Wang, Anxin; Xie, Xuewei; Tian, Xue; Johnston, S. Claiborne; Li, Hao; Bath, Philip M.; Zuo, Yingting; Jing, Jing; Lin, Jinxi; Wang, Yilong; Zhao, Xingquan; Li, Zixiao; Jiang, Yong; Liu, Liping; Meng, Xia; Wang, Yongjun

Abstract

Background:
Evidence on the risk–benefit ratio of dual antiplatelet therapies among patients with stroke and impaired renal function is limited and inconsistent.

Objective:
To investigate the effect of renal function on the efficacy and safety of ticagrelor–aspirin versus clopidogrel–aspirin treatment.

Design:
Post hoc analysis of a multicenter, randomized, double-blind, placebo-controlled trial. (ClinicalTrials.gov: NCT04078737)

Setting:
202 centers in China.

Patients:
CYP2C19 loss-of-function allele carriers with minor stroke or transient ischemic attack.

Intervention:
Ticagrelor–aspirin and clopidogrel–aspirin.

Measurements:
Renal function was evaluated by estimated glomerular filtration rate (eGFR) levels. The primary efficacy and safety outcomes were recurrent stroke and severe or moderate bleeding within 90 days, respectively.

Results:
Among 6378 patients, 4050 (63.5%) had normal (eGFR ≥90 mL/min/1.73 m2), 2010 (31.5%) had mildly decreased (eGFR 60 to 89 mL/min/1.73 m2), and 318 (5.0%) had moderately to severely decreased (eGFR <60 mL/min/1.73 m2) renal function. The corresponding differences in recurrent stroke between ticagrelor–aspirin and clopidogrel–aspirin for normal, mildly decreased, and moderately to severely decreased renal function was −2.8 percentage points (95% CI, −4.4 to −1.3 percentage points) (hazard ratio [HR], 0.63 [CI, 0.49 to 0.81]), −0.2 percentage point (CI, −2.4 to 2.0 percentage points) (HR, 0.98 [CI, 0.69 to 1.39]), and 3.7 percentage points (CI, −2.3 to 10.1 percentage points) (HR, 1.31 [CI, 0.48 to 3.55]), respectively. Rates of severe or moderate bleeding did not substantially differ by treatment assignments across eGFR categories.

Limitation:
Renal function was only evaluated by using eGFR, and the proportion of patients with severely decreased renal function was low.

Conclusion:
Patients with normal, rather than impaired, renal function received greater benefit from ticagrelor–aspirin versus clopidogrel–aspirin.

Citation

Wang, A., Xie, X., Tian, X., Johnston, S. C., Li, H., Bath, P. M., …Wang, Y. (2022). Ticagrelor–Aspirin Versus Clopidogrel–Aspirin Among CYP2C19 Loss-of-Function Carriers With Minor Stroke or Transient Ischemic Attack in Relation to Renal Function: A Post Hoc Analysis of the CHANCE-2 Trial. Annals of Internal Medicine, 175(11), 1534-1542. https://doi.org/10.7326/M22-1667

• Journal Article Type: Article
• Acceptance Date: Sep 18, 2022
• Online Publication Date: Nov 1, 2022
• Publication Date: Nov 1, 2022
• Deposit Date: Nov 7, 2022
• Journal: Annals of Internal Medicine
• Print ISSN: 0003-4819
• Electronic ISSN: 1539-3704
• Publisher: American College of Physicians
• Peer Reviewed: Peer Reviewed
• Volume: 175
• Issue: 11
• Pages: 1534-1542
• DOI: https://doi.org/10.7326/M22-1667
• Keywords: General Medicine, Internal Medicine
• Public URL: https://nottingham-repository.worktribe.com/output/13182000
• Publisher URL: https://www.acpjournals.org/doi/10.7326/M22-1667