Intravenous S18886 caused a dose-dependent prolongation in the time to primary occlusive coronary artery thrombosis compared to vehicle (up to 92.4 vs 43.3 minutes).
Does S18886 alone or combined with clopidogrel prevent coronary arterial thrombosis in a canine model?
In a canine model, the thromboxane receptor antagonist S18886 delays coronary thrombosis and prevents occlusion when combined with clopidogrel.
Absolute Event Rate: 92.4% vs 43.3%
The specific thromboxane receptor antagonist, S18886, was evaluated for prevention of coronary arterial thrombosis and myocardial ischemia-reperfusion in anesthetized canines. For the primary thrombosis study in left circumflex (LCX) coronary artery, 26 dogs were randomized to receive either vehicle (n = 7) or intravenous S18886 (0.3 mg/kg, n = 6; 1.0 mg/kg, n = 6; and 3.0 mg/kg, n = 7). The respective times to occlusion after S18886 were as follows: 56.8 +/- 9.3, 83.5 +/- 14.9, and 92.4 +/- 15.7 minutes compared to 43.3 +/- 8.2 minutes after vehicle. S18886 caused a minimal increase in tongue bleeding time and a significant decrease in ex vivo platelet aggregation to arachidonic acid or U46619. Another 37 dogs were randomized to receive placebo (n = 12), clopidogrel 1.0 mg/kg p.o. QDX3 (n = 9), clopidogrel + S18886 0.3 (n = 9) or 1.0 (n = 7) mg/kg intravenous. Clopidogrel produced a 50% reduction in adenosine diphosphate-induced platelet aggregation and a slight increase in the time to occlusion. However, clopidogrel + S18886 1.0 mg/kg prevented occlusive thrombus formation in most of the coronary vessels over 6 hours. S18886 did not alter myocardial infarct size in the ischemia-reperfusion model. In conclusion, S18886 alone caused a dose-dependent prolongation in the time to primary occlusive coronary artery thrombosis, whereas S18886 + clopidogrel displayed effective in preventing occlusive thrombus formation with only a moderate increase of tongue-bleeding time.
Hong et al. (Wed,) conducted a other in Coronary arterial thrombosis and myocardial ischemia-reperfusion (n=63). S18886 vs. Vehicle was evaluated on Time to occlusion. Intravenous S18886 caused a dose-dependent prolongation in the time to primary occlusive coronary artery thrombosis compared to vehicle (up to 92.4 vs 43.3 minutes).