Recombinant tissue plasminogen activator in acute thrombotic and embolic stroke

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 intracerebral hemorrhage were prerequisites for treatment. After the 60-minute rt-PA infusion, arterial perfusion was assessed 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 (M2) and branch (M3) occlusions were more likely to undergo recanalization by 60 minutes than were internal carotid artery occlusions. Hemorrhagic infarction occurred 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 occurred 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.

Early Recanalization After Intravenous Administration of Recombinant Tissue Plasminogen Activator as Assessed by Pre- and Post-Thrombolytic Angiography in Acute Ischemic Stroke Patients

“…The recanalization rates evaluated by angiographies that were performed before and after IV 2-chain rt-PA treatment (0.12 to 0.75 MIU/kg) were 8% in the extracranial ICA, 26.1% in the proximal MCA, and 38.1% in the distal MCA occlusion. 7 A study using 100 mg of rt-PA demonstrated recanalization rates of 9% in the ICA, 38.8% in the proximal MCA, and 100% in the distal MCA occlusion. 8 Our data are consistent with those studies in that it shows very low recanalization rates in the ICA and proximal MCA occlusions.…”

Intra-arterial treatment in acute ischaemic stroke: What we learn from the MR CLEAN trial

“…2 We already know that the chances of recanalisation with IV t-PA are even more limited in cases of proximal large artery occlusions. In a landmark study 3 it was shown that the overall chances of recanalisation with IV thrombolysis are around 30%, but less when the thrombi are in the middle cerebral artery stem (24%) or in the proximal internal carotid artery (8%).…”

Intravenous Recombinant Tissue Plasminogen Activator Improves Arterial Recanalization Rates and Reduces Infarct Volumes in Patients With Hyperdense Artery Sign on Baseline Computed Tomography

“…Recent analysis confirms that some of this recanalization may be within the first 30-60 minutes after rt-PA treatment. [12][13][14][15][16] Advances in CT and MR angiography as well as TCD now allow non-invasive evaluation of patency and recanalization of intracranial arterial occlusions not available in the mid-1990's.…”