NEW YORK (Reuters Health) – An investigational agent, ARC1779, reduces cerebral emboli resulting from carotid endarterectomy by inhibiting the prothrombotic effects of von Willebrand factor (vWF), according to a report in the August issue of Stroke.

“Our results show for the first time that vWF inhibition improves a clinically relevant end point, cerebral embolization in humans,” the authors say.

Dr. Hugh S. Markus, at St George’s University of London, and colleagues in the UK explain that ARC1779 is an aptamer antagonist that blocks the A1 domain of vWF and inhibits vWF-dependent platelet functions. “Aptamers are a novel therapeutic class of oligonucleotides with drug-like properties that share some attributes of monoclonal antibodies as well as some of those of low-molecular weight chemically synthesized drugs.”

The researchers investigated the effects of ARC1779 on cerebral embolization in patients after carotid endarterectomy (CEA), because embolic signals on Doppler ultrasound (rather than clinical events) are frequent and so efficacy can be demonstrated in relatively small patient numbers.

In the trial, 36 patients undergoing CEA were randomly assigned to receive ARC1779 or placebo intravenously 1 hour before the procedure and for 3.5 hours after. Transcranial Doppler recording was performed for 3 hours beginning 30 minutes after skin closure.

The team found the median time to first embolic signals was 83.6 minutes in the ARC1779 patients compared with 5.5 minutes in the placebo group (p=0.007).

The median number of embolic signals during the 3 postoperative hours was 1.0 in the ARC1779 group compared with 5.5 in the placebo group (p=0.08), the researchers report. In fact, 7 of 18 subjects in the ARC1779 group had no embolic signal whereas they were detected in all of the placebo patients (p=0.0105).

Bleeding was the only adverse event that occurred more often in the ARC1779 group, with one serious and six non-serious bleeding events compared to none in the placebo group, according to the report.

The antiplatelet effect of ARC1779 could be useful in the treatment of stroke and MI, the authors suggest. They conclude, “Further studies are now required to determine both whether this treatment approach reduces clinical cardiovascular events and to assess the risk of bleeding complications in a nonoperative situation.”

Reference:
The von Willebrand Inhibitor ARC1779 Reduces Cerebral Embolization After Carotid Endarterectomy
Stroke. 2011;42.