Inhibition of Platelet Aggregation by AZD6140, A Reversible Oral P2Y12 Receptor Antagonist, Compared With Clopidogrel in Patients With Acute Coronary Syndromes
Robert F. Storey, MD*,1,*,
Steen Husted, MD ,1,
Robert A. Harrington, MD, FACC ,1,
Stanley Heptinstall, PhD ,1,
Robert G. Wilcox, MD,1,
Gary Peters, MD||,2,
Mark Wickens, BSc¶,2,
Håkan Emanuelsson, MD, PhD#,2,
Paul Gurbel, MD, FACC**,1,
Peer Grande, MD and
Christopher P. Cannon, MD, FACC,1
* Cardiovascular Research Unit, University of Sheffield, Sheffield, United Kingdom
Department of Medicine and Cardiology, Århus University Hospital, Århus, Denmark
Division of Cardiovascular Medicine, Duke Clinical Research Institute, Durham, North Carolina
Cardiovascular Medicine, University of Nottingham, Nottingham, United Kingdom
|| AstraZeneca R&D, Wilmington, Delaware
¶ AstraZeneca R&D, Charnwood, United Kingdom
# AstraZeneca R&D, Mölndal, Sweden
** Sinai Center for Thrombosis Research, Baltimore, Maryland
Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
TIMI Study Group, Cardiovascular Division, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts.
View larger version (22K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 2 Inhibition of Platelet Aggregation After Initial Doses of Clopidogrel and AZD6140
Mean percentage inhibition of platelet aggregation derived from (A) maximum aggregation response and (B) final aggregation response at 6 min after addition of adenosine diphosphate 20 µmol/l, for clopidogrel-naïve patients before and after clopidogrel 300 mg (n = 14), AZD6140 90 mg (n = 9), AZD6140 180 mg (n = 7), or AZD6140 270 mg (n = 15). Error bars show standard deviation and points are nudged on the X axis only to reveal error bars. *p < 0.05 for AZD6140 versus clopidogrel.
|
|
View larger version (12K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 3 Individual Responses to Clopidogrel and AZD6140
Individual area-under-the-curve data for inhibition of platelet aggregation derived from final aggregation response at 6 min after addition of ADP 20 µmol/l, for clopidogrel-naïve patients (A) after the first dose of either clopidogrel 300 mg, AZD6140 90 mg, AZD6140 180 mg, or AZD6140 270 mg and (B) after 4 weeks of treatment and after next dose of either clopidogrel 75 mg, AZD6140 90 mg, or AZD6140 180 mg. Data are for the first 8 h of treatment but are representative of the smaller numbers for whom data were available for the full 12 h. The lines indicate mean values. *p < 0.05 for AZD6140 versus clopidogrel. ADP = adenosine diphosphate; IPA = inhibition of platelet aggregation; other abbreviations as in Figure 1.
|
|
View larger version (19K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 4 Steady-State and 24 h Postdose Inhibition of Platelet Aggregation by Clopidogrel and AZD6140
Mean percentage inhibition of platelet aggregation both after 4 weeks of study medication (clopidogrel-naïve patients) and 24 h after discontinuation of study medication derived from (A) maximum aggregation response and (B) final aggregation response at 6 min after addition of adenosine diphosphate 20 µmol/l, before and after the next dose of either clopidogrel 75 mg (n = 10), AZD6140 90 mg (n = 15), or AZD6140 180 mg (n = 10). Error bars show standard deviation and points are nudged on the X axis only to reveal error bars. *p < 0.05 for AZD6140 versus clopidogrel; p < 0.05 for clopidogrel predose versus 2 h postdose.
|
|
View larger version (19K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 5 Suppression of Platelet Aggregation by AZD6140 in Clopidogrel-Pretreated Patients
Mean percentage platelet aggregation derived from final aggregation response at 6 min after addition of adenosine diphosphate 20 µmol/l, for clopidogrel-pretreated patients before and after either clopidogrel 75 mg (n = 12) or the first dose of AZD6140 90 mg (n = 9), AZD6140 180 mg (n = 7), or AZD6140 270 mg (n = 16). Error bars show standard deviation and points are nudged on the X axis only to reveal error bars. *p < 0.05 for AZD6140 versus clopidogrel.
|
|
|
