Antiplatelet loading improves behavioral outcome in a rabbit model of stroke.

Background And Purpose: No approved acute therapy exists for thousands of patients with ischemic stroke who present ineligible for thrombolytics. The purpose of this proof-of-concept study was to evaluate the efficacy of acute antiplatelet loading on stroke outcome in the rabbit small clot embolic model.

Methods: Sixty male New Zealand white rabbits were embolized via small clots into the middle cerebral artery. Two hours later, animals were treated with (1) aspirin (5 mg/kg; n=20); (2) usual dual antiplatelet loading (aspirin 10 mg/kg+clopidogrel 10 mg/kg; n=20); or (3) high-dose dual antiplatelet loading (aspirin 10 mg/kg+clopidogrel 30 mg/kg; n=20). The coprimary outcomes were as follows: (1) platelet inhibition and (2) behavioral outcome as measured by the P50 (milligrams of clot that leads to neurological dysfunction in 50% of animals in a group).

Results: There was a significant difference in 3-hour arachidonic acid and ADP (P<0.011); 6-hour collagen and ADP (P<0.01, P<0.01); and 24-hour collagen, arachidonic acid, and ADP (P=0.02, P<0.01, P<0.01) platelet inhibition. The behavioral outcome was significantly better in the usual dual antiplatelet loading versus aspirin group (P=0.02).

Conclusions: This study suggests that usual dual antiplatelet loading is clinically beneficial in a validated model of acute stroke. Study of usual dual antiplatelet loading in acute stroke is warranted to provide treatment to stroke victims ineligible for current therapies.