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Inhibition of platelet aggregation by AZD6140, a reversible oral P2Y12 receptor antagonist, compared with clopidogrel in patients with acute coronary syndromes.

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  • Robert F Storey, Cardiovascular Research Unit, University of Sheffield, Sheffield, United Kingdom
  • Steen Husted, Denmark
  • Robert A Harrington, Division of Cardiovascular Medicine, Duke Clinical Research Institute, Durham, North Carolina, United States
  • Stanley Heptinstall, Cardiovascular Medicine, University of Nottingham, Nottingham, United Kingdom
  • Robert G Wilcox, Cardiovascular Medicine, University of Nottingham, Nottingham, United Kingdom
  • Gary Peters, AstraZeneca R&D, Charnwood, United Kingdom
  • Mark Wickens, AstraZeneca R&D, Charnwood, United Kingdom
  • Håkan Emanuelsson, AstraZeneca R&D, Mölndal, Sweden
  • Paul Gurbel, Sinai Center for Thrombosis Research, Baltimore, Maryland, United States
  • Peer Grande, Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
  • Christopher P Cannon, TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States
  • The Department of Internal Medicine and Cardiology A
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.
Udgivelsesdato: 2007-Nov-6
Original languageEnglish
JournalJournal of the American College of Cardiology
Pages (from-to)1852-6
Number of pages4
Publication statusPublished - 2007

    Research areas

  • Acute Coronary Syndrome, Administration, Oral, Aged, Dose-Response Relationship, Drug, Drug Administration Schedule, Electrocardiography, Female, Humans, Male, Middle Aged, Myocardial Infarction, Platelet Aggregation, Platelet Aggregation Inhibitors, Receptors, Purinergic P2, Ticlopidine

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