Randomized Double-Blind Assessment of the ONSET and OFFSET of the Antiplatelet Effects of Ticagrelor Versus Clopidogrel in Patients With Stable Coronary Artery Disease

Abstract

Background-Ticagrelor is the first reversibly binding oral P2Y 12 receptor antagonist. This is the first study to compare the onset and offset of platelet inhibition (IPA) with ticagrelor using the PLATO (PLATelet inhibition and patient Outcomes) trial loading dose (180 mg) with a high loading dose (600 mg) of clopidogrel. 0001).At 24 hours after the last dose, mean IPA was 58% for ticagrelor versus 52% for clopidogrel (PϭNS). IPA for ticagrelor on day 3 after the last dose was comparable to clopidogrel at day 5; IPA on day 5 for ticagrelor was similar to clopidogrel on day 7 and did not differ from placebo (PϭNS). Conclusions-Ticagrelor achieved more rapid and greater platelet inhibition than high-loading-dose clopidogrel; this was sustained during the maintenance phase and was faster in offset after drug discontinuation. Clinical Trial Registration Information-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00528411.

How to manage prasugrel and ticagrelor in daily practice

“…Since ticagrelor reversibly binds to the P2Y12 receptor, the recovery of platelet function after discontinuation is faster than that after cessation of clopidogrel. In the overall ONSET-OFFSET cohort [21], platelet reactivity at 3 days after ticagrelor withdrawal was similar to that observed at 5 days after clopidogrel withdrawal.…”

“…Two hours after a 180 mg loading dose of ticagrelor, inhibition of platelet aggregation is more pronounced (mean ± SD, 88 ± 15%) than after a 600 mg loading dose of clopidogrel (38 ± 33%); this difference persists during the maintenance therapy [21]. Since ticagrelor reversibly binds to the P2Y12 receptor, the recovery of platelet function after discontinuation is faster than that after cessation of clopidogrel.…”

Ticagrelor-Associated Bleeding in a Patient Undergoing Surgery for Acute Type A Aortic Dissection

“…In the ONSET/OFFSET study, inhibition of platelet aggregation was significantly higher in the ticagrelor group compared with the clopidogrel group 8 hours after the last study drug intake but did not differ between the groups at 24 and 48 hours after the last dose. 3 This could possibly be translated into an increased risk of bleeding in ticagrelor-treated patients compared with clopidogrel-treated patients when surgery is performed within 24 hours after drug intake.…”

“…However, the use of prasugrel is associated with greater postoperative bleeding than clopidogrel. 2,3 Whether or not prasugrel therapy increases the incidence of postoperative bleeding complications is unknown. There are few reports on the management of major bleeding in patients on prasugrel prior to surgery, and the reversal of prasugrelinduced platelet inhibition with platelet transfusion has not been reported.…”

Antiplatelet Therapy of Acute Coronary Syndrome: Current Capab Ilities

“…данные доказательной медицины Результаты многочисленных исследований про-демонстрировали, что прасугрел и тикагрелор быстрее и выраженнее ингибируют активность тромбоцитов у пациентов с различными формами ишемической болезни сердца [15][16][17][18][19].…”