Platelet Reactivity in Acute Non-disabling Cerebrovascular Events

Summary

Ticagrelor is a reversible and direct-acting oral antagonist of the P2Y12 (Purinergic receptor P2Y, G-protein coupled, 12) receptor for adenosine diphosphate, which provides faster, greater, and more consistent P2Y12 inhibition than Clopidogrel in patients with acute coronary syndrome, irrespective of the genetic variants affecting Clopidogrel metabolism. It is still undefined whether combination therapy of Ticagrelor and Aspirin is more effective than Clopidogrel and aspirin for minor stroke and transient ischemic attack (TIA). The primary purpose of the PRINCE trial is to evaluate the anti-platelet effects of a 3-month regimen of ticagrelor initiated with 180 mg loading dose followed by 90 mg twice/day combined with aspirin 100 mg/day during first 21 days versus a 3-month regimen of clopidogrel initiated with 300 mg loading dose of followed by 75 mg/day combined with aspirin 100 mg/day during first 21 days when initiated within 24 hours of symptom onset in high-risk transient ischemic attack or minor stroke.

Timeline

Start

2015-08

Primary completion

2017-03

Completion

2018-03

Outcome

Met primary endpoint

paper At 90 days, high platelet reactivity occurred in 35 (12.5%) of 280 patients in the ticagrelor/aspirin group and 86 (29.7%) of 290 patients in the clopidogrel/aspirin group PMID 31171523 ↗

paper risk ratio 0.40; 95% confidence interval 0.28 to 0.56; P<0.001 PMID 31171523 ↗

Publications

• Yang Y, Chen W, Pan Y, Yan H, Meng X, Liu L, Wang Y, Wang Y. Ticagrelor Is Superior to Clopidogrel in Inhibiting Platelet Reactivity in Patients With Minor Stroke or TIA. Front Neurol. 2020 Jun 10;11:534. doi: 10.3389/fneur.2020.00534. eCollection 2020.
• Yang Y, Chen W, Meng X, Liu L, Wang Y, Pan Y, Wang Y. Impact of smoking on platelet function of ticagrelor versus clopidogrel in minor stroke or transient ischaemic attack. Eur J Neurol. 2020 May;27(5):833-840. doi: 10.1111/ene.14171. Epub 2020 Mar 8.
• Wang Y, Chen W, Lin Y, Meng X, Chen G, Wang Z, Wu J, Wang D, Li J, Cao Y, Xu Y, Zhang G, Li X, Pan Y, Li H, Zhao X, Liu L, Lin J, Dong K, Jing J, Johnston SC, Wang D, Wang Y; PRINCE Protocol Steering Group. Ticagrelor plus aspirin versus clopidogrel plus aspirin for platelet reactivity in patients with minor stroke or transient ischaemic attack: open label, blinded endpoint, randomised controlled phase II trial. BMJ. 2019 Jun 6;365:l2211. doi: 10.1136/bmj.l2211.
• Wang Y, Lin Y, Meng X, Chen W, Chen G, Wang Z, Wu J, Wang D, Li J, Cao Y, Xu Y, Zhang G, Li X, Pan Y, Li H, Liu L, Zhao X, Wang Y; PRINCE Protocol Steering Group. Effect of ticagrelor with clopidogrel on high on-treatment platelet reactivity in acute stroke or transient ischemic attack (PRINCE) trial: Rationale and design. Int J Stroke. 2017 Apr;12(3):321-325. doi: 10.1177/1747493017694390. Epub 2017 Jan 1.

Drugs

Evaluation	Drug	Modality	Dose	Route
Comparator	Clopidogrel	Small molecule	75 mg	—
Subject	Ticagrelor	Small molecule	90 mg	Oral
Background	Aspirin	Small molecule	100 mg	—

Indications