Glycoprotein IIb/IIIa antagonists in acute ischaemic stroke - Current status and future directions

Glycoprotein (GP) IIb/IIIa receptors on the surface of platelets play a critical role in thrombosis. Intravenous GP IIb/IIIa antagonists abciximab, tirofiban and eptifibatide have demonstrated efficacy in acute coronary syndromes when combined with heparin, aspirin, clopidogrel and percutanous coronary interventions. Results have been less consistent in acute ischaemic stroke. Preclinical data support the potential benefit of these agents both in the microcirculation and in aiding clot lysis. While phase I and 11 trials of abciximab as the sole agent employing dosages comparable with those used in coronary syndromes were promising, the pivotal phase III trial was abandoned because of an unfavourable benefit-to-risk ratio. New preliminary platelet inhibition measurements from our group suggest that cardiac dosages were likely to be too high for stroke patients. Exploration of lower dosages of abciximab and potentiation with time-limited weight-based heparin along with platelet aggregation inhibition measurement is continuing on a smaller scale. At present, the most common usage of GP IIb/IIIa antagonists in stroke are as adjunctive agents to thrombolysis by intravenous and intra-arterial routes. Substantial progress is likely to require a better understanding of the mechanism of actions and unique pharmacology of GP IIb/IIIa antagonists in ischaemic stroke.