Data Management And Sharing System of China National Clinical Research Center for Neurological Diseases
Effects of remnant cholesterol on the efficacy of genotype-guided dual antiplatelet in CYP2C19 loss-of -function carriers with minor stroke or transient ischaemic attack: a post-hoc analysis of the CHANCE-2 trial
First author：Anxin Wang,Xue Tian
Corresponding author：Yongjun Wang,Xia Meng
essential_information
- Person in charge：Anxin Wang,Xue Tian
- Data Sources： CHANCE-2
- Number of papers：CHANCE-220240001
- Published time：2023-12-02
2023-12-02
Published articles
Journal：EClinicalMedicine
Publication type: Original Contributions
IF(IF): 15.1
PMID: 38125963 Link To Pubmed Full text Download
Background And Purpose
The atherogenicity of remnant cholesterol (RC), a contributor to residual risk of cardiovascular events, has been underlined by recent guidelines. We aimed to evaluate the relationship between RC levels and the efficacy and safety of genotype-guided dual antiplatelet therapy in the CHANCE-2 trial.
Method
This post-hoc study used data from the CHANCE-2 trial, which was a randomised, double-blind, placebo-controlled trial of 6412 patients (aged >40 years) enrolled from 202 hospitals in China, between Sept 23, 2019, and March 22, 2021, who carried CYP2C19 loss-of-function alleles and had either an acute minor stroke or high-risk transient ischaemic attack (TIA), and could start treatment within 24 h of symptom onset. Participants received either (1:1) ticagrelor plus aspirin (control) or clopidogrel plus aspirin (intervention) and the effect of reducing the 3-month risk of any new stroke was assessed (ischemic or haemorrhagic, primary outcome). From the CHANCE-2 study population, we enrolled 5890 patients with complete data on RC. The cutoff point of RC for distinguishing patients with greater benefit from ticagrelor-aspirin versus clopidogrel-aspirin was determined with subpopulation treatment effect pattern plot. The primary efficacy and safety outcome was recurrent stroke and severe or moderate bleeding within 90 days, respectively. CHANCE-2 is registered with ClinicalTrials.gov, NCT04078737.
Conclusion
Our post-hoc findings suggest that RC could be a potential biomarker to discriminate patients who received more benefits from ticagrelor-aspirin versus clopidogrel-aspirin therapy in CYP2C19 loss-of-function carriers with minor stroke or TIA. These findings need to be validated in an independent study.
Main results
The cutoff to define elevated RC was 0.91 mmol/L. Ticagrelor-aspirin versus clopidogrel-aspirin was associated with a reduced risk of recurrent stroke in patients with non-elevated RC levels (122 [5.3%] versus 179 [7.8%]; hazard ratio [HR], 0.68; 95% confidence interval [CI], 0.54-0.85), but this benefit was absent in those with elevated RC levels (58 [8.4%] versus 48 [7.3%]; HR, 1.10; 95% CI, 0.73-1.65; P-interaction = 0.03). When analyzed as a continuous variable, the benefit of ticagrelor-aspirin on recurrent stroke decreased as RC levels increased. The rates of severe or moderate bleeding between treatment groups were similar across RC categories (0.3% versus 0.3%, P-interaction = 0.95).