Brief History of Endovascular Acute Ischemic Stroke Treatment

The natural history of large-vessel extracranial and intracranial arterial occlusion has played a major role in the evolution of endovascular stroke therapy. Basilar artery occlusion was felt to have the worst prognosis, and this drove Zeumer et al1 to first perform basilar thrombolysis via catheter and report excellent outcomes based on historical controls. However, early stroke thrombolysis clinical trials focused on intravenous (IV) and not intraarterial (IA) delivery. Gregory del Zoppo—a hematologist by training—led international angiography-based, dose escalation trials of double-stranded tissue-type plasminogen activator (tPA) given IV. This Burroughs Wellcome–sponsored research trial showed that distal M3 middle cerebral artery (MCA) occlusions often recanalized with IV tPA, but recanalization rates were low with more proximal large-vessel occlusions. Furthermore, the site of arterial occlusion could not be reliably predicted by clinical phenotype or National Institutes of Health Stroke Scale (NIHSS). Concurrent with this angiography-based effort, the National Institute of Neurological Disorders and Stroke (NINDS) investigators downplayed the need for angiography and instead focused on time to treatment with IV tPA. The NINDS Genentech IV tPA stroke trial established the critical importance of time to treatment and led to Food and Drug Administration (FDA) approval of IV tPA to treat acute ischemic stroke in 1996 but within a small window of 3 hours.The major drivers for the development of endovascular stroke therapy were the desire to expand the 3-hour treatment window and the relatively low recanalization rates for large-vessel occlusions with IV tPA (which often caused the most severe strokes). Toward this end, Gregory Del Zoppo, Anthony Furlan, Randall Higashida, and Michael Pessin convinced Abbott Laboratories that the quickest way to FDA approval of their new thrombolytic agent recombinant prourokinase (r-proUK) was an IA trial focused only on MCA occlusion. Accordingly, Del Zoppo, Furlan, Higashida, and Pessin designed the Prolyse in …