Inhibition of platelet aggregation by AZD6140, A reversible oral P2Y12 receptor antagonist, compared with clopidogral in patients with acute coronary syndrome

被引:400
作者
Storey, Robert F.
Husted, Steen
Harrington, Robert A.
Heptinstall, Stanley
Wilcox, Robert G.
Peters, Gary
Wickens, Mark
Emanuelsson, Hakan
Gurbel, Paul
Grande, Peer
Cannon, Christopher P.
机构
[1] Univ Sheffield, Sch Med & Biomed Sci, Cardiovasc Res Unit, Sheffield S10 2RX, S Yorkshire, England
[2] Arhus Univ Hosp, Dept Med & Cardiol, Aarhus, Denmark
[3] Duke Clin Res Inst, Div Cardiovasc Dis, Durham, NC USA
[4] Univ Nottingham, Nottingham NG7 2RD, England
[5] AstraZeneca R&D, Wilmington, DE USA
[6] AstraZeneca R&D, Molndal, Sweden
[7] Sinai Ctr Thrombosis Res, Baltimore, MD USA
[8] Copenhagen Univ Hosp, Rigshosp, Dept Cardiol, Copenhagen, Denmark
[9] Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA
[10] Harvard Univ, Sch Med, Boston, MA USA
关键词
D O I
10.1016/j.jacc.2007.07.058
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objectives In a substudy of DISPERSE (Dose confirmation Study assessing anti-Platelet Effects of AZD6140 vs. clopidogRel in non-ST-segment Elevation myocardial infarction)-2, we compared the antiplatelet effects of AZD6140 and clopidogrel and assessed the effects of AZD6140 in clopidogrel-pretreated patients. Background Clopidogrel, in combination with aspirin, reduces cardiovascular events in patients with acute coronary syndromes (ACS). However, patients with poor inhibition of platelet aggregation with clopidogrel may be less well protected. AZD6140 is a reversible oral P2Y(12) receptor antagonist that has been studied in ACS patients in comparison with clopidogrel (DISPERSE-2 study). Methods Patients were randomized to receive either AZD6140 90 mg twice a day, AZD6140 180 mg twice a day, or clopidogrel 75 mg once a day for up to 12 weeks in a double-blind, double-dummy design. One-half the patients allocated AZD6140 received a 270-mg loading dose. Patients randomized to receive clopidogrel were given a 300-mg loading dose unless they had already been treated with clopidogrel. Adenosine diphosphate-induced platelet aggregation was assessed by optical aggregometry on day 1 and at 4-week intervals. Results AZD6140 inhibited platelet aggregation in a dose-dependent fashion and both doses achieved greater levels of inhibition than clopidogrel (e.g., 4 weeks, 4-h postdose [mean (+/- SD)]: clopidogrel 64% [+/- 22%], AZD6140 90 mg 79% [+/- 22%], AZD6140 180 mg 95% [+/- 8%]. AZD6140 also produced further suppression of platelet aggregation in patients previously treated with clopidogrel. Conclusions AZD6140 exhibited greater mean inhibition of platelet aggregation than a standard regimen of clopidogrel in ACS patients. In addition, AZD6140 further suppressed platelet aggregation in clopidogrel pretreated patients.
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页码:1852 / 1856
页数:5
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