Defining Intravenous Recombinant Tissue Plasminogen Activator Failure

Although the 2 National Institute of Neurological Disorders and Stroke (NINDS) trials1 and subsequent studies from Europe (ECASS-3, IST-3)2,3 established intravenous (IV) thrombolysis with recombinant tissue plasminogen activator (rtPA) within 4.5 hours of symptom onset as an effective treatment for acute ischemic stroke, the ability of IV rtPA to predictably result in an excellent outcome is still limited; in most cases, IV rtPA treatment is not enough to produce complete recanalization.4,5Intraarterial (endovascular) treatment (IAT) is superior to IV rtPA in opening arteries, particularly when coupled with mechanical thrombectomy, with recanalization rates up to 87%.6,7 There is increasing evidence that IAT has a therapeutic role in large artery occlusions.8,9 In addition, faster time to angiographic reperfusion is a predictor of good clinical outcome with IAT.10 Thus, there is a need for a quick and accurate strategy to identify IV rtPA nonresponders with large artery occlusion to select those patients who would benefit from IAT.Mechanical Embolus Removal in Cerebral Ischemia (MERCI), Multi MERCI, and Solitaire With the Intention For Thrombectomy (SWIFT) are just a few of the studies that have used the concept of IV rtPA failure as inclusion criteria to enroll subjects in their studies. But what exactly is the definition of IV tPA nonresponder or failure? To date, there is no clear and consistent designation for this subgroup in the stroke literature. How do the characteristics of the clot influence response to IV rtPA? Is there a time window that should define IV rtPA failure? Should imaging modalities to assess vessel recanalization be used to define IV rtPA failure? Should early clinical change be criteria to differentiate IV rtPA responders from nonresponders? Accurate and rapid identification …