Equipoise among recanalization strategies

Abstract

Modern acute ischemic stroke therapy is based on the premise that recanalization and subsequent reperfusion are essential for the preservation of brain tissue and favorable clinical outcomes. We outline key issues that we think underlie equipoise regarding the comparative clinical efficacy of IV recombinant tissue-type plasminogen activator (rt-PA) and intra-arterial (IA) reperfusion therapies for acute ischemic stroke. On the one hand, IV rt-PA therapy has the benefit of speed with presumed lower rates of recanalization of large artery occlusions as compared to IA methods. More recent reports of major arterial occlusions treated with IV rt-PA, as measured by transcranial Doppler and magnetic resonance angiography, demonstrate higher rates of recanalization. Conversely, IA therapies report higher recanalization rates, but are hampered by procedural delays and risks, even failing to be applied at all in occasional patients where time to reperfusion remains a critical factor. Higher rates of recanalization in IA trials using clot-removal devices have not translated into improved patient functional outcome as compared to trials of IV therapy. Combined IV-IA therapy promises to offer advantages of both, but perhaps only when applied in the timeliest of fashions, compared to IV therapy alone. Where equipoise exists, randomizing subjects to either IV rt-PA therapy or IV therapy followed by IA intervention, while incorporating new interventions into the study design, is a rational and appropriate research approach.

Figure 1 Rankin outcomes by time to IA therapy mRankin 0–2 outcomes according to time to IA therapy (patterned bars) are depicted for a pre-IMS registry, IMS I, and IMS II. For subjects with NIH Stroke Scale score 10 or greater who were less than 81 years old, and who were treated intra-arterially after 3 hours, mRankin 0–2 outcomes in multicenter IV-IA trials have not differed significantly from those achieved in patients of similar age and stroke severity treated with IV rt-PA within 3 hours in the NINDS rt-PA trial (depicted as white bar). IA = intra-arterial; IMS = Interventional Management of Stroke; mRankin = modified Rankin score; NINDS = National Institute of Neurological Disorders and Stroke; rt-PA = recombinant tissue-type plasminogen activator.

Figure 2 Rankin outcomes in IMS and NINDS trials by ASPECTS score Ninety-day mRS in IMS I (IV-IA tPA) subjects with a baseline ASPECTS Score greater than 7. Comparison groups are NINDS rt-PA Stroke Trial subjects treated with rt-PA and placebo who also had baseline ASPECTS score >7. IA = intra-arterial; IMS = Interventional Management of Stroke; mRS = modified Rankin score; NINDS = National Institute of Neurological Disorders and Stroke; tPA = tissue-type plasminogen activator.