Intra-Arterial Fibrinolysis for Acute Ischemic Stroke

Abstract

See related article, pages 2633–2639. For nearly a decade, intra-arterial fibrinolytic therapy for acute ischemic stroke has stood poised on the threshold of a definitive evidential basis and widespread acceptance. The positive result of the phase 3 PROACT II trial in 1999 appeared to validate the pathophysiologically eminently reasonable strategy of endovascular recanalization in acute ischemic stroke.1 Endovascular therapy delivers lytic agent at high concentration directly to the clot, increasing lysis rates compared with intravenous therapy, while minimizing systemic exposure and extracerebral bleeding complications.2 Leading stroke centers adopted endovascular recanalization therapies as a common off-label treatment option for patients beyond the 3-hour window.3 However, proponents of evidence-based medicine noted that a single, small phase 3 clinical trial was insufficient to provide definitive proof of efficacy. The US Food and Drug Administration and international regulatory agencies did not approve a stroke label for pro-urokinase. The expense of a confirmatory phase 3 trial of pro-urokinase proved daunting to pharma and none was undertaken. In US national practice guidelines, intra-arterial fibrinolysis occupied a gray zone, receiving a Level B recommendation, indicating the incomplete foundation of a single dose-ranging and single positive phase 3 trial.4 The limitations of this evidential base have prevented regional emergency medical systems from organizing delivery of patients directly to endovascular hospitals. The results of the MELT trial, reported in this issue of Stroke , are therefore very welcome, providing additional information regarding intra-arterial fibrinolytic therapy that complements and supports previous studies. …