Summary
Application of clopidogrel before percutaneous coronary intervention in patients with
acute coronary syndrome reduces the risk of cardiac events. Clopidogrel administration
before surgery increases bleeding complications after CABG. Therefore, the antithrombotic
effect of the low-dose combination of clopidogrel and aspirin was investigated in
an in vivo pig model of coronary artery thrombus formation with cyclic flow reductions. The
platelet inhibitory effect was determined by platelet aggregation and CFR, according
to the methodology described by Folts. CFR were initiated by endothelial damage and
placement of a constrictor around the LAD. 30 min after CFR were established, clopidogrel
(0.1 mg/kg or5 mg/kg), aspirin (1 mg/kg or 7 mg/kg) or LDC (0.1 mg/kg clopidogrel
and 1 mg/kg aspirin) were administered orally. CFR-frequency was determined for further
240 min. CFR-frequency (CFR/30 min) was significantly reduced at 60 min in response
to aspirin (7 mg/kg, −48%, p<0.05), and at 120 min in response to clopidogrel (5 mg/kg,
−65%, p<0.05) but not at low doses of either compound. In contrast, LDC of clopidogrel
(0.1 mg/kg) plus aspirin (1 mg/kg) resulted in a complete and rapid abrogation of
CFR at 90 min (−70%, p<0.05). Furthermore, LDC led to reduction of platelet aggregation
when CFR-frequency was already significantly decreased. In contrast, high dose groups
presented a significant reduction of platelet aggregation prior to CFR-frequency decrease.
Low dose combination of clopidogrel plus aspirin demonstrates a potent over additive
anti-thrombotic effect in vivo with a significant reduction in thrombus formation early after drug application.
The effect occurs before inhibition of platelet aggregation is detectable.
Keywords
Aspirin - clopidogrel - platelets - acute coronary syndrome - coronary artery bypass
grafting
