Abstract 5495: More Rapid and Consistent Inhibition of Platelet Aggregation is Achieved by Loading With Ticagrelor Compared to Clopidogrel in Patients With Acute Coronary Syndromes: Results From the PLATO PLATELET Substudy

Abstract

Background: Ticagrelor (T) is an oral reversible P2Y 12 receptor antagonist that does not require conversion to an active metabolite for antiplatelet activity, unlike clopidogrel (C). The PLATO study compared the efficacy of T and C in patients with a broad range of acute coronary syndromes (ACS). In this substudy (PLATO PLATELET), we assessed the onset and extent of inhibition of platelet function in PLATO study patients. Methods and Results: 24 C-naive patients with NSTE ACS or STEMI undergoing primary PCI and sequentially randomised in a double blind, double dummy design to C (300mg [n=7] or 600 mg load [n=5]) or T (180mg load [n=12]) in the PLATO study in a single centre were entered into the first phase of PLATO PLATELET. Light transmittance aggregometry (LTA) with ADP (5 and 20 uM) and whole blood single platelet counting aggregometry (WBSPC) using ADP 1–100 uM was performed prior to study drug administration and 1, 2, 4, 8 and 12 hours after study drug. VerifyNow P2Y12 (VN) and VASP assays were also performed pre and 4h post study drug. Data obtained after abciximab administration was excluded except for VASP data. There was more rapid and greater inhibition of platelet aggregation with T vs C, with most T-treated patients showing a substantial effect at 1h post dose that was sustained until 12h post dose (Figure ). VN data at 4h were 273±124 and 68±97 PRU for C and T respectively (p<0.01). VASP data showed a similar trend. C 300 vs 600mg doses showed the same patterns of LTA response. Conclusion: T 180mg loading dose has a faster onset of action with greater inhibition of platelet function compared to C in patients with ACS. WBSPC and VN can rapidly assess the early effects of P2Y 12 antagonists.