Time, Flow, and Location Key to Lytic Sufficiency for Stroke
Recanalization factors pinned down in prospective analysis
How
responsive an intracranial thrombus is to alteplase (Activase) depends
on certain factors that could help inform how patients with acute
ischemic stroke should be triaged, according to a global prospective
cohort study.
IV alteplase was associated with higher odds of successful recanalization, at 30.4% versus 13.3% for non-recipients (difference 17.1%, 95% CI 10.2%-25.8%) among the 575 stroke patients with intracranial occlusions observed on CT angiography in the INTERRSeCT study, reported online in JAMA by Andrew Demchuk, MD, of University of Calgary in Alberta, and collaborators.
Among those getting alteplase, the factors associated with recanalization of the arterial occlusion were:
"Patients with factors associated with thrombus responsiveness to alteplase (e.g., thrombus permeability) may not require transfer because they will recanalize with IV alteplase," Demchuk's group suggested.
The stroke patients in the study -- from 12 centers across North America, Europe, and East Asia -- had a median 114 minutes elapse from the last time they were known to be well to baseline CT angiography, 19 minutes between baseline CT angiography to the start of alteplase administration, and then another 132.5 minutes to recanalization assessment.
"The results of this study suggest that recanalization with IV alteplase is a continuous process over time," the authors said. "With a plasma half-life of 6 to 7 minutes, alteplase is not likely to be biologically active at 6 hours following administration. However, it is possible that the early thrombus debulking effects of alteplase translate to less overall thrombus, allowing endogenous tissue plasminogen activator [tPA] to complete the remaining lysis required."
The INTERRSeCT findings may be relevant in deciding where to send stroke patients who are potential candidates for endovascular therapy, the investigators suggested.
"When transport times are several hours longer to a comprehensive stroke center compared with a primary stroke center, evaluation at a primary stroke center for initial treatment with IV alteplase is likely the better option based on reasonable recanalization rates with alteplase over several hours," they said.
This is the most important message of this study, according to Brian Silver, MD, of UMass Memorial Health Care in Worcester, Massachusetts.
"What the actual distance or time duration should be is not clear at this time, but anything over 60 minutes probably does not warrant diversion to a comprehensive stroke center because of potential negative implications for the patient," he said in an interview.
On the other hand, Tudor Jovin, MD, of the University of Pittsburgh Medical Center, wasn't completely on board.
"This is another piece in the puzzle but it doesn't solve the puzzle [of how to triage patients]," he told MedPage Today. "By the time patients get to CT angiography to determine the level and characteristics of the occlusion, the patient is already at the primary stroke center."
The "holy grail" would be to have this information in the field, before hospital arrival, Jovin said. This may be possible with mobile stroke units (which have yet to prove their cost-effectiveness, he noted) or the use of transcranial ultrasound in ambulances.
Another issue is the need for more refined predictive capabilities: "Even if you identify some patients who have, say, a 70% chance of opening up with IV tPA, is that enough to send them to a non-thrombectomy place? None of these methods detect the chance of recanalization with tPA to a level where we are actually comfortable taking a patient to a non-thrombectomy center," cautioned Jovin.
Nevertheless, he called Demchuk's study "very important," because it confirms with prospective data what other retrospective studies had previously suggested about recanalization rates. "We can now put more reliable numbers when we plan trials and things like that -- the recanalization rate of tPA in someone with internal carotid artery occlusion [for example] ... We now have better numbers to quote."
One caveat to the study, Demchuk and colleagues acknowledged, was that patients were enrolled in 2010-2016, during a period of significant evolution in stroke care. Additionally, the sample was relatively small and precluded subset analyses by occlusion site.
Study participants were a median 72 years old and 51.5% men. Treatments provided were alteplase only (47.8%), alteplase plus endovascular thrombectomy (33.9%), thrombectomy alone (8.3%), and conservative treatment (9.9%).
IV alteplase was associated with higher odds of successful recanalization, at 30.4% versus 13.3% for non-recipients (difference 17.1%, 95% CI 10.2%-25.8%) among the 575 stroke patients with intracranial occlusions observed on CT angiography in the INTERRSeCT study, reported online in JAMA by Andrew Demchuk, MD, of University of Calgary in Alberta, and collaborators.
Among those getting alteplase, the factors associated with recanalization of the arterial occlusion were:
- Time from treatment start to recanalization assessment: OR 1.28 for every 30-minute interval (95% CI 1.18-1.38)
- More distal thrombus location: OR 5.61 (95% CI 2.38-13.26)
- Greater residual flow: OR 7.03 (95% CI 3.32-14.87)
"Patients with factors associated with thrombus responsiveness to alteplase (e.g., thrombus permeability) may not require transfer because they will recanalize with IV alteplase," Demchuk's group suggested.
The stroke patients in the study -- from 12 centers across North America, Europe, and East Asia -- had a median 114 minutes elapse from the last time they were known to be well to baseline CT angiography, 19 minutes between baseline CT angiography to the start of alteplase administration, and then another 132.5 minutes to recanalization assessment.
"The results of this study suggest that recanalization with IV alteplase is a continuous process over time," the authors said. "With a plasma half-life of 6 to 7 minutes, alteplase is not likely to be biologically active at 6 hours following administration. However, it is possible that the early thrombus debulking effects of alteplase translate to less overall thrombus, allowing endogenous tissue plasminogen activator [tPA] to complete the remaining lysis required."
The INTERRSeCT findings may be relevant in deciding where to send stroke patients who are potential candidates for endovascular therapy, the investigators suggested.
"When transport times are several hours longer to a comprehensive stroke center compared with a primary stroke center, evaluation at a primary stroke center for initial treatment with IV alteplase is likely the better option based on reasonable recanalization rates with alteplase over several hours," they said.
This is the most important message of this study, according to Brian Silver, MD, of UMass Memorial Health Care in Worcester, Massachusetts.
"What the actual distance or time duration should be is not clear at this time, but anything over 60 minutes probably does not warrant diversion to a comprehensive stroke center because of potential negative implications for the patient," he said in an interview.
On the other hand, Tudor Jovin, MD, of the University of Pittsburgh Medical Center, wasn't completely on board.
"This is another piece in the puzzle but it doesn't solve the puzzle [of how to triage patients]," he told MedPage Today. "By the time patients get to CT angiography to determine the level and characteristics of the occlusion, the patient is already at the primary stroke center."
The "holy grail" would be to have this information in the field, before hospital arrival, Jovin said. This may be possible with mobile stroke units (which have yet to prove their cost-effectiveness, he noted) or the use of transcranial ultrasound in ambulances.
Another issue is the need for more refined predictive capabilities: "Even if you identify some patients who have, say, a 70% chance of opening up with IV tPA, is that enough to send them to a non-thrombectomy place? None of these methods detect the chance of recanalization with tPA to a level where we are actually comfortable taking a patient to a non-thrombectomy center," cautioned Jovin.
Nevertheless, he called Demchuk's study "very important," because it confirms with prospective data what other retrospective studies had previously suggested about recanalization rates. "We can now put more reliable numbers when we plan trials and things like that -- the recanalization rate of tPA in someone with internal carotid artery occlusion [for example] ... We now have better numbers to quote."
One caveat to the study, Demchuk and colleagues acknowledged, was that patients were enrolled in 2010-2016, during a period of significant evolution in stroke care. Additionally, the sample was relatively small and precluded subset analyses by occlusion site.
Study participants were a median 72 years old and 51.5% men. Treatments provided were alteplase only (47.8%), alteplase plus endovascular thrombectomy (33.9%), thrombectomy alone (8.3%), and conservative treatment (9.9%).
Demchuk reported receiving honoraria for CME events from Medtronic.
Jovin and Silver disclosed no conflicts of interest.
Jovin and Silver disclosed no conflicts of interest.
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