Key result
AZD6140 provides greater platelet inhibition than clopidogrel in acute coronary syndromes, reaching ~79% to 95%.
Why the study?
Patients with ACS treated with clopidogrel may have poor inhibition of platelet aggregation, and the antiplatelet effects of AZD6140 compared with clopidogrel needed evaluation.
Does AZD6140 improve inhibition of platelet aggregation compared to clopidogrel in patients with acute coronary syndromes?
RCT
Double-blind, double-dummy
Randomized
Does AZD6140 improve inhibition of platelet aggregation compared to clopidogrel in patients with acute coronary syndromes?
AZD6140 achieves greater, dose-dependent inhibition of platelet aggregation compared to clopidogrel in patients with acute coronary syndromes.
Answers are grounded in this paper and cite their sources.
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“The hypothesis is that a new antiplatelet therapy that can offer a higher level of inhibition of platelet aggregation could have an even greater clinical benefit. This would need to be tested in a large clinical trial, but the data today are an important step: precisely because there has been concern in the past that with a higher level of inhibition one might expect to see an increased risk of bleeding. In the current study, this was not the case with AZD6140.”
AZD6140 yields greater platelet inhibition than clopidogrel in ACS; supports dose selection for subsequent outcome trials.
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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Storey et al. (2007) conducted an RCT in Acute Coronary Syndromes. AZD6140 vs. Clopidogrel 75 mg once a day was evaluated on Adenosine diphosphate-induced platelet aggregation at 4 weeks, 4-h postdose. AZD6140 (90 mg or 180 mg twice daily) achieved greater inhibition of platelet aggregation at 4 weeks compared to clopidogrel in patients with acute coronary syndromes (79% and 95% vs 64%).
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