Pharmacodynamics, pharmacokinetics and safety of ticagrelor in Asian patients with stable coronary artery disease
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ORIGINAL ARTICLE
Pharmacodynamics, pharmacokinetics and safety of ticagrelor in Asian patients with stable coronary artery disease Y. Hiasa • R. Teng • H. Emanuelsson
Received: 3 December 2013 / Accepted: 30 May 2014 Ó Japanese Association of Cardiovascular Intervention and Therapeutics 2014
Abstract This randomized, active-controlled, doubleblind study assessed the pharmacodynamics, pharmacokinetics and safety of ticagrelor in Japanese patients and a smaller cohort of non-Japanese Asian patients. The study recruited patients aged 20–80 years who had received aspirin 75–100 mg/day for C2 weeks and had percutaneous coronary intervention or acute coronary syndrome [3 months previously. Patients received 4 weeks’ treatment with ticagrelor 45 mg bid, ticagrelor 90 mg bid or clopidogrel 75 mg qd (all with aspirin). The inhibition of platelet aggregation (IPA, final-extent) and pharmacokinetics of ticagrelor were assessed on days 1 and 28. Overall, 139 Asian patients were randomized (ticagrelor 45 mg bid, n = 50; ticagrelor 90 mg bid, n = 43; clopidogrel, n = 46) of whom 118 were Japanese. Mean finalextent IPA was greater with ticagrelor 90 mg bid versus ticagrelor 45 mg bid and with both ticagrelor doses versus clopidogrel. At the end of the dosing interval on day 28, mean final-extent IPA was 10.0 % higher (95 % confidence interval 0.5–19.5 %) for ticagrelor 90 mg bid versus ticagrelor 45 mg bid, 15.1 % higher (5.8–24.4 %) for ticagrelor 45 mg bid versus clopidogrel, and 25.1 % higher (15.5–34.7 %) for ticagrelor 90 mg bid versus clopidogrel. In Japanese patients, exposure to ticagrelor and its active metabolite AR-C124910XX increased dose-proportionally.
Y. Hiasa Department of Cardiology, Tokushima Red Cross Hospital, Tokushima, Japan R. Teng AstraZeneca, Wilmington, DE, USA H. Emanuelsson (&) AstraZeneca R&D, Pepparredsleden 1, 43138 Mo¨lndal, Sweden e-mail: [email protected]
The safety profile of ticagrelor was consistent with previous studies. Ticagrelor was associated with enhanced IPA versus clopidogrel in Japanese patients. Keywords Ticagrelor Pharmacokinetics Pharmacodynamics P2Y12 receptor antagonist Japanese
Introduction Ticagrelor is an orally active P2Y12 receptor antagonist [1, 2] used for the prevention of atherothrombotic events in patients with acute coronary syndrome (ACS) [3]. The efficacy and safety of ticagrelor in patients with ACS was investigated in the PLATelet inhibition and patient Outcomes (PLATO) trial [4]; ticagrelor plus aspirin reduced the rate of the primary composite endpoint of myocardial infarction, stroke or death from vascular causes relative to clopidogrel plus aspirin. Although the rate of major bleeding not related to coronary artery bypass grafting was higher in the ticagrelor group than the clopidogrel group, no treatment-group difference in the rate of overall major bleeding was observed in PLATO. After oral administration, ticagrelor is rapidly absorbed and displays a linear and predictable pharmacokinetic (PK) profile [5–8]. Although ticagrelor
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