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 language | English (US) |
|---|---|
| Pages (from-to) | 1852-1856 |
| Number of pages | 5 |
| Journal | Journal of the American College of Cardiology |
| Volume | 50 |
| Issue number | 19 |
| DOIs | |
| State | Published - Nov 6 2007 |
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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 journal › Article
}
TY - JOUR
T1 - Inhibition of Platelet Aggregation by AZD6140, A Reversible Oral P2Y12 Receptor Antagonist, Compared With Clopidogrel in Patients With Acute Coronary Syndromes
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.
PY - 2007/11/6
Y1 - 2007/11/6
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.
UR - http://www.scopus.com/inward/record.url?scp=35548933800&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=35548933800&partnerID=8YFLogxK
U2 - 10.1016/j.jacc.2007.07.058
DO - 10.1016/j.jacc.2007.07.058
M3 - Article
VL - 50
SP - 1852
EP - 1856
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
SN - 0735-1097
IS - 19
ER -