Abstract WP68: Extending the Time Window with Low Dose IV Abciximab in Acute Non-Lacunar Stroke
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Background: Proven options to treat ischemic stroke patients ineligible for IV t-PA are limited. Our focus is on treatments to spare the penumbral microcirculation. Evidence indicates that Glycoprotein (GP) IIb/IIIa inhibitors when given with heparin, as used in coronary intervention, increases macro- and distal micro-vascular patency in the heart and animal stroke models. We hypothesized that the cardiac dose of IV abciximab (ABX) used in the halted AbESTT trial was too high leading to hemorrhage, while exclusion of heparin reduced efficacy. We previously showed that a 30% lower ABX dose achieved target GP IIb/IIIa platelet inhibition of 92% in stroke patients and hypothesized a lower dose when given with short term heparin would be safe and effective.
Methods: After consent, patients with non-lacunar stroke ineligible for t-PA were offered low dose IV ABX (bolus:0.2 mg/kg & infusion:0.05 ug/kg/hr) along with IV heparin (36 hrs) for ant. circulation strokes within 6 hrs and post. within 12 hrs of onset. In place of a control arm, we adapted our pPAIRS matching strategy to obtain best matches from non-lacunar placebo patients in the NINDS dataset at the 2 hr post-randomization NIHSS. Age, glucose and gender were other factors that were matched.
Results: Forty five patients have been treated. t-PA ineligibility was mostly due to time of onset, recent surgery or anticoagulation. Mean time to treatment was 5.2 h (Ant:4.1h; Post:9.3h). Matching with NINDS placebo subjects was excellent: median NIHSS: ABX: 18 vs NINDS: 17; age: ABX: 66.6 13 vs NINDS: 66.3 11; and glucose: ABX:148 58 vs NINDS:144 52; all p>0.05. There was 1 symptomatic hemorrhage in ABX patients (2.2%) vs none in NINDS; p=1.0. Ninety day mRS 0-1 and 0-2 in the ABX arm (42.2% and 55.6%) were higher than in NINDS matched placebo subjects (15.6% and 31.1%); all p<0.05. Mortality was 24% after ABX and 40% in NINDS; p>.05.
Conclusion: Low dose ABX appeared safe and potentially effective when compared with NINDS placebo subjects assessed 2 hrs after their initial presentation so as to provide a comparable baseline. Since low dose ABX achieves sufficient platelet inhibition and the combination with short term heparin appeared well tolerated, we suggest these findings deserve confirmation in a prospective RCT.