Abstract 3292: AZD6140 Exerts Greater Inhibition of Platelet Aggregation than Clopidogrel in Patients with Stable Atherosclerotic Disease or Unstable Coronary Disease
Background: AZD6140, the first reversible oral antagonist of the platelet P2Y12 receptor, was compared with clopidogrel (CLOP) in the DISPERSE and DISPERSE2 studies of pts with stable atherosclerotic disease and non-ST-elevation ACS, respectively. We analyzed inhibition of platelet aggregation (IPA) data from both studies.
Methods: Pts with stable atherosclerotic disease were given AZD6140 50, 100 or 200 mg BID or 400 mg QD or CLOP 75 mg QD for 28 days; pts with non-ST-elevation ACS were given AZD6140 90 mg or 180 mg BID or CLOP 300 mg, then 75 mg daily for up to 12 wks. Optical aggregometry with ADP 20 μM was performed in DISPERSE and in a DISPERSE2 substudy. We compared the effects of AZD6140 and CLOP at steady state (maximum level of inhibition) after 28 days’ treatment by evaluating final IPA (6 min after addition of ADP). Individual area-under-curve (AUC) values were determined for IPA to assess consistency of response.
Results: Steady-state IPA by CLOP was the same in stable and ACS pts (mean [±SD] final IPA, 4 h post-dose: DISPERSE, 64 ± 19.5%; DISPERSE2, 64 ± 22.3%). The highest AZD6140 doses yielded consistently high levels of inhibition in stable and ACS pts (mean [±SD] final IPA, 4 h post-dose: DISPERSE/AZD6140 100 mg, 88 ± 11.9%; DISPERSE/AZD6140 200 mg, 94 ± 8.7%; DISPERSE/AZD6140 400 mg, 95 ± 7.4%; DISPERSE2/AZD6140 90 mg, 79 ± 21.8%, DISPERSE2/AZD6140 180 mg, 95 ±7.5%). In both studies, AZD6140 inhibited PA in a dose-dependent fashion and all but 50 mg BID yielded substantially greater mean AUC values for IPA than CLOP (Fig⇓).
Conclusions: AZD6140, at doses greater than 50 mg BID, yields greater and more consistent IPA than clopidogrel 75 mg QD in pts with stable atherosclerotic disease or ACS.