Recombinant tissue plasminogen activator in acute thrombotic and embolic stroke

TLDR

Acute focal cerebral ischemia due to carotid or vertebrobasilar arterial occlusion, without detectable intracerebral hemorrhage, is the clinical scenario for rt‑PA treatment. The study was an open, angiography‑based, dose‑rate escalation trial of intravenous rt‑PA to assess cerebral arterial recanalization in acute ischemic stroke patients across 16 centers. Among 139 patients treated at a mean of 5.4 h after symptom onset, IV rt‑PA showed no dose‑rate effect on recanalization, M2/M3 occlusions recanalized more often than ICA, hemorrhagic transformation occurred in 20.2 % (hemorrhagic infarction) and 10.6 % (parenchymatous hematoma) with higher rates after ≥6 h, yet all events were within safety guidelines and unrelated to recanalization.

Abstract

Abstract An open angiography‐based, dose rate escalation study on the effect of intravenous infusion of recombinant tissue plasminogen activator(rt‐PA) on cerebral arterial recanalization in patients with acute focal cerebral ischemia was performed at 16 centers. Arterial occlusions consistent with acute ischemia in the carotid or vertebrobasilar territory in the absence of detectable intracerebal hemorrhage were prerequisites for treatment. After the 60‐minute rt‐PA infusion, arterial perfusion was assesed by repeat angiography and computed tomography scans were performed at 24 hours to assess hemorrhagic transformation, Of 139 patients with symptoms of focal ischemia, 80.6% (112) had complete occlusion of the primary vessel at a mean of 5.4 ± 1.7 hours after symptom onset. No dose rate response of cerebral arterial recanalization was observed in 93 patients who completed the rt‐PA infusion. Middle cerebral artery division (M 2 ) and branch (M 3 ) occlusions were more likely to undergo recanalization by 60 minutes than were internal carotid artery occlusions. Hemorrhagic infarction occured in 20.2% and parenchymatous hematoma in 10.6% of patients over all dose rates, while neurological worsening accompanied hemorrhagic transformation (hemorrhagic infarction and parenchymatous hematoma) in 9.6% of patients. All findings were within prospective safety guidelines. No dose rate correlation with hemorrhagic infarction, parenchymatous hematoma, or both was seen. Hemorrhagic transformation occured significantly more frequently in patients receiving treatment at least 6 hours after symptom onset. No relationship between hemorrhagic transformation and recanalization was observed. This study indicates that site of occlusion, time to recanalization, and time to treatment are important variables in acute stroke intervention with this agent.