Inhibition of Platelet Aggregation by AZD6140, A Reversible Oral P2Y12 Receptor Antagonist, Compared With Clopidogrel in Patients With Acute Coronary Syndromes

Robert F. Storey, Steen Husted, Robert A. Harrington, Stanley Heptinstall, Robert G. Wilcox, Gary Peters, Mark Wickens, Håkan Emanuelsson, Paul Gurbel, Peer Grande, Christopher P. Cannon

Research output: Contribution to journalArticle

Abstract

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 P2Y12 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.

Original languageEnglish (US)
Pages (from-to)1852-1856
Number of pages5
JournalJournal of the American College of Cardiology
Volume50
Issue number19
DOIs
StatePublished - Nov 6 2007

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clopidogrel
Purinergic P2Y Receptor Antagonists
Acute Coronary Syndrome
Platelet Aggregation
Ticagrelor

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  • Nursing(all)

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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. / Storey, Robert F.; Husted, Steen; Harrington, Robert A.; Heptinstall, Stanley; Wilcox, Robert G.; Peters, Gary; Wickens, Mark; Emanuelsson, Håkan; Gurbel, Paul; Grande, Peer; Cannon, Christopher P.

In: Journal of the American College of Cardiology, Vol. 50, No. 19, 06.11.2007, p. 1852-1856.

Research output: Contribution to journalArticle

Storey, RF, Husted, S, Harrington, RA, Heptinstall, S, Wilcox, RG, Peters, G, Wickens, M, Emanuelsson, H, Gurbel, P, Grande, P & Cannon, CP 2007, 'Inhibition of Platelet Aggregation by AZD6140, A Reversible Oral P2Y12 Receptor Antagonist, Compared With Clopidogrel in Patients With Acute Coronary Syndromes', Journal of the American College of Cardiology, vol. 50, no. 19, pp. 1852-1856. https://doi.org/10.1016/j.jacc.2007.07.058
Storey, Robert F. ; Husted, Steen ; Harrington, Robert A. ; Heptinstall, Stanley ; Wilcox, Robert G. ; Peters, Gary ; Wickens, Mark ; Emanuelsson, Håkan ; Gurbel, Paul ; Grande, Peer ; Cannon, Christopher P. / Inhibition of Platelet Aggregation by AZD6140, A Reversible Oral P2Y12 Receptor Antagonist, Compared With Clopidogrel in Patients With Acute Coronary Syndromes. In: Journal of the American College of Cardiology. 2007 ; Vol. 50, No. 19. pp. 1852-1856.
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abstract = "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 P2Y12 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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AU - Storey, Robert F.

AU - Husted, Steen

AU - Harrington, Robert A.

AU - Heptinstall, Stanley

AU - Wilcox, Robert G.

AU - Peters, Gary

AU - Wickens, Mark

AU - Emanuelsson, Håkan

AU - Gurbel, Paul

AU - Grande, Peer

AU - Cannon, Christopher P.

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N2 - 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 P2Y12 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.

AB - 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 P2Y12 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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