Data Management And Sharing System of China National Clinical Research Center for Neurological Diseases
Aspirin platelet reactivity on platelet function and clinical outcome in minor stroke or transient ischemic attack
First author：Yanjie Xu,Weiqi Chen
Corresponding author：Yilong Wang,Yuesong Pan
essential_information
- Person in charge：Yanjie Xu,Weiqi Chen
- Data Sources： PRINCE
- Number of papers：PRINCE20210041
- Published time：2022-07-29
2022-07-29
Published articles
Journal：Journal of Stroke & Cerebrovascular Diseases
Publication type: Clinical Article
IF(IF): 2.677
PMID: 35914511 Link To Pubmed Full text Download
Background And Purpose
Patients with acute minor stroke and transient ischaemic attack (TIA) are the most common acute cerebrovascular disease，which are at high risk of recurrent stroke[1]. Short‐term dual antiplatelet therapy with clopidogrel and aspirin is beneficial for prevention of stroke recurrence [2–6]. The Platelet Reactivity In acute Non-disabling Cerebrovascular Events (PRINCE) trial showed that ticagrelor was an ideal antiplatelet therapy for clopidogrel resistant patients with minor stroke/TIA[7]. Persistence of ischemic events despite appropriate anti-platelet therapy is referred to antiplatelet resistance [8]. In such patients, an insufficient degree of inhibition of platelet activation measured by in vitro assays is termed high on-treatment platelet reactivity (HTPR), or laboratory resistance. HTPR is associated with poor cerebrovascular outcomes, and might be of clinical value for the evaluation of recurrent events in patients with stroke.9-12 However, in combination antiplatelet therapy, there is a lack of studies on the interaction of HTPR between different drugs and its effect on clinical outcomes. In this subgroup analysis of the PRINCE trial, we aimed to investigate whether high aspirin platelet reactivity differed between ticagrelor and clopidogrel platelet responsiveness and clinical outcomes in patients with acute mild stroke or TIA.
Method
We compared the proportion of HPR-P2Y12 between the two treatment groups based on aspirin platelet reactivity using genmod models adjusted by the HPR-P2Y12 status at baseline, reported as a risk ratio with 95% confidence interval (CI). The differences in the risks of clinical outcomes during 90‐day follow‐up were assessed by Cox proportional hazards regression and were reported as hazard ratios with 95% CI.
Conclusion
: In patients with minor stroke or TIA, clopidogrel, and particularly ticagrelor, decreased platelet function in poor versus good aspirin responders. The poor platelet reactivity of aspirin could not sufficiently reduce the risk of recurrent stroke with ticagrelor or clopidogrel; however, HPR (poor aspirin response) may have a protective effect on clinically relevant major bleeding.
Main results
Among 628 enrolled patients, 69 (11%) were poor aspirin responders. After 7 § 2 days, the proportion of poor P2Y12 responders for ticagrelor versus clopidogrel significantly reduced in poor (2.6% versus 27.4%) and good (14.3% versus 29.4%) aspirin responders. There were significant interactions between treatment groups, and between treatment groups and aspirin platelet reactivity for poor P2Y12 responders (P = 0.01). After 90 § 7 days, there were no significant interactions between treatment groups and aspirin platelet reactivity for new stroke risk (good aspirin responders: 5.5% versus 8.8%, hazard ratio [HR]: 0.61; 95% confidence interval [CI], 0.32 to 1.16; P = 0.13; poor aspirin responders: 8.6% versus 8.8%, HR: 0.97, 95% CI: 0.20 4.81; P = 0.97; P for interaction = 0.60). Major bleeding was less frequent in poor than good aspirin responders (ticagrelor/aspirin: 0.4%/0%; clopidogrel/aspirin: 1.4%/0%).