I thank Dr Kabra for his comments on my article, “Intra-arterial thrombolysis within 3 hours after acute ischemic stroke in selected patients,”1 When I made the statement that rescue intra-arterial thrombolysis in internal carotid artery occlusion resulted in reperfusion, which was correlated with outcome, it simply meant that where reperfusion was achieved, the outcomes were better.
This is also evidence from the Interventional Management of Stroke trial overall results that 62 of the 77 patients required intra-arterial rescue therapy after the abbreviated dose of intravenous recombinant tissue plasminogen activator. Of this subset, 56% recanalized after rescue intra-arterial therapy, and of these, 34% achieved an excellent outcome. Without successful reperfusion, the rest (12%) achieved a dismal modified Rankin score of 0 to 1. The point of my article, substantiated by the Interventional Management of Stroke-2 trial,2 was that intravenous thrombolysis is best reserved for branch occlusion–related ischemic stroke, where transcranial Doppler has demonstrated successful reperfusion, whereas for large-vessel occlusion, intravenous thrombolysis rarely achieves successful reperfusion, again based on transcranial Doppler data.
Whereas the pivotal National Institute of Neurological Disorders and Stroke trial demonstrated a good outcome across all stroke subtypes, they were arbitrarily based on TOAST criteria, not vascular or penumbral imaging, which provides a more valid and homogeneous grouping.2,3 When analyzed by stroke severity, as based on the National Institutes of Health Stroke Scale (NIHSS), patients with large-vessel occlusions with an expected NIHSS score >20 did poorly, with an absolute risk reduction of <7%, not the 12% to 13% overall results depicted in the primary outcome of the study. Finally, because randomized, prospective trials are not inclusive or representative of all stroke subtypes, there will be subgroups who do better and those who do not. PROACT, a 6-hour intra-arterial pro-urokinase trial in patients with documented M1 middle cerebral artery occlusion, and the Multi-MERCI Trial, which used the MERCI Device up to 8 hours afterward in large-vessel occlusions in patients with ischemic stroke, demonstrated outcomes comparable to those of the National Institute of Neurological Disorders and Stroke 3-hour window, based on treatment with intravenous recombinant tissue plasminogen activator, where the overall NIHSS scores were lower, suggesting that in the National Institute of Neurological Disorders and Stroke trial, there was a greater proportion of milder strokes and possibly branch occlusions rather than mainstem internal carotid or basilar artery occlusions.4,5
Ongoing studies, including MR RESCUE and IMS111, are using image-based, population-selection criteria and may provide the final answer for this ongoing controversy, that is, whether the present US Food and Drug Administration–approved intravenous thrombolytic therapy is better than intra-arterial interventions for large-vessel ischemic stroke (in the M1 middle cerebral, internal carotid, and basilar artery). IMS111 may also shed some light on the safety of the current practice in many tertiary stroke centers of administering full-dose intravenous recombinant tissue plasminogen activator and then “chasing” it with intra-arterial rescue intervention, the combination being mistakenly labeled as a US Food and Drug Administration–approved standard of care, in the absence of any prospective, randomized trial demonstrating the safety or efficacy of this combination.
Moonis M. Intra-arterial thrombolysis within 3 hours after acute ischemic stroke in selected patients. Stroke. 2009; 40: 2611–2612.
The IMS Study Investigators. Combined intravenous and intra-arterial recanalization for acute ischemic stroke: the Interventional Management of Stroke Study. Stroke. 2004; 35: 904–911.
del Zoppo GJ, Higashida RT, Furlan AJ, Pessin MS, Rowley HA, Gent M. PROACT: a phase II randomized trial of recombinant pro-urokinase by direct arterial delivery in acute middle cerebral artery stroke. PROACT Investigators; Prolyse in Acute Cerebral Thromboembolism. Stroke. 1998; 29: 4–11.
Smith WS, Sung G, Saver J, Budzik R, Duckwiler G, Liebeskind DS, Lutsep HL, Rymer MM, Higashida RT, Starkman S, Gobin YP; Multi MERCI Investigators, Frei D, Grobelny T, Hellinger F, Huddle D, Kidwell C, Koroshetz W, Marks M, Nesbit G, Silverman IE. Mechanical thrombectomy for acute ischemic stroke: final results of the Multi MERCI Trial. Stroke. 2008; 39: 1205–1212.