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.

Background-The antiplatelet effects of the Platelet Inhibition and Patient Outcomes (PLATO) trial dose of ticagrelor in patients nonresponsive to clopidogrel and after they switch agents are unknown. Methods and Results-Patients with stable coronary artery disease on aspirin therapy received a 300-mg clopidogrel load; nonresponders were identified by light transmittance aggregometry. In a 2-way crossover design, nonresponders (nϭ41) and responders (nϭ57) randomly received clopidogrel (600 mg/75 mg once daily) or ticagrelor (180 mg/90 mg twice daily) for 14 days during period 1. In period 2, all nonresponders switched treatment; half of the responders continued the same treatment, whereas the others switched treatment. Inhibition of platelet aggregation was higher in nonresponders treated with ticagrelor compared with clopidogrel (PϽ0.05). Treatment with ticagrelor among nonresponders resulted in a Ͼ10%, Ͼ30%, and Ͼ50% decrease in platelet aggregation from baseline in 100%, 75%, and 13% of patients, respectively. Platelet aggregation fell from 59Ϯ9% to 35Ϯ11% in patients switched from clopidogrel to ticagrelor and increased from 36Ϯ14% to 56Ϯ9% in patients switched from ticagrelor to clopidogrel (PϽ0.0001 for both). Platelet reactivity was below the cut points previously associated with ischemic risk measured by light transmittance aggregometry, VerifyNow P2Y 12 assay, and vasodilator-stimulated phosphoprotein phosphorylation in 98% to 100% of patients after ticagrelor therapy versus 44% to 76% of patients after clopidogrel therapy. Conclusions-Ticagrelor therapy overcomes nonresponsiveness to clopidogrel, and its antiplatelet effect is the same in responders and nonresponders. Nearly all clopidogrel nonresponders and responders treated with ticagrelor will have platelet reactivity below the cut points associated with ischemic risk. Clinical Trial Registration-http://www.clinicaltrials.gov.