Abciximab in acute ischemic stroke. A randomized, double-blind, placebo-controlled, dose-escalation study.
OBJECTIVE
Abciximab is a potent parenterally administered platelet glycoprotein IIb/IIIa antagonist. Because this agent has been shown to improve outcomes in coronary artery disease, there is interest to evaluate whether it could improve cerebral perfusion and outcomes after ischemic stroke. This study was designed to evaluate the safety of abciximab in acute ischemic stroke and to obtain pilot efficacy data.


METHODS
We conducted a randomized, double-blind, placebo-controlled, dose-escalation trial. Seventy-four eligible and consenting patients presenting within 24 hours after ischemic stroke onset at 38 study sites were randomly allocated to receive either an escalating dose of abciximab (54 patients) or placebo (20 patients) in a ratio of 3:1. We studied 4 escalating doses of abciximab. Patients underwent a scheduled follow-up head CT scan 24 to 36 hours after the completion of study agent administration to monitor for bleeding complications and were evaluated through 3 months.


RESULTS
There were no cases of major intracranial hemorrhage. Asymptomatic parenchymal hemorrhages were detected on post-study agent CT in 4 of 54 abciximab patients (7%) and in 1 of 20 placebo patients (5%). Six additional abciximab patients had asymptomatic hemorrhagic lesions detected by unscheduled brain imaging during their follow-up period. Nine of 11 patients with asymptomatic hemorrhage had a baseline National Institutes of Health Stroke Scale score >14. At 3 months, there was a trend toward a higher rate of minimal residual disability (Barthel Index > or =95 or modified Rankin scale < or =1) among abciximab patients compared with those who received placebo.


CONCLUSIONS
Abciximab appears to be safe when administered up to 24 hours after stroke onset, and it might improve functional outcome.
Department of Neurology, University of Iowa, Iowa City 52242-1053, USA.
D000077284:Abciximab; D000208:Acute Disease; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002545:Brain Ischemia / Q000000981:diagnostic imaging / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007902:Length of Stay; D008297:Male; D008875:Middle Aged; D010919:Placebos; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011859:Radiography; D012449:Safety; D020521:Stroke / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000401:mortality; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D010919:Placebos; D010975:Platelet Aggregation Inhibitors; D000077284:Abciximab