For Your Patients-Acute Ischemic Stroke
The Clinical Characteristics that Could Help in Triaging Patients for tPA or Thrombectomy
By Mark Moran
October 18, 2018
ARTICLE IN BRIEF
Researchers elucidated the clinical, imaging, and thrombus characteristics that could potentially help in triaging patients in the field to either receiving intravenous tissue plasminogen activator (tPA) or transport to a thrombectomy center.
A more distal thrombus location, greater thrombus permeability, and longer time to recanalization assessment appear to be associated with successful recanalization following intravenous alteplase in patients with acute ischemic stroke, according to a September 11 report in the Journal of the American Medical Association.
The study elucidates clinical, imaging, and thrombus characteristics that could potentially help in triaging patients in the field to either receiving intravenous tissue plasminogen activator (tPA) or transport to a thrombectomy center.
“Our study provides some extra color in terms of decision-making around whether patients should receive tPA or thrombectomy,” said corresponding author Andrew M. Demchuk, MD, professor of neurology at the University of Calgary in Alberta, Canada. “If the clot is remote and has porosity, tPA is very likely to work in that situation. That's a patient who doesn't need to bother with a long transport to a thrombectomy center, because tPA will likely open the clot. In other situations where the carotid artery is involved, tPA has a very low likelihood of success,” Dr. Demchuk said.
STUDY DETAILS, FINDINGS
The INTERRSeCT (Identifying New Approaches to Optimize Thrombus Characterization for Predicting Early Recanalization and Reperfusion With IV Alteplase and Other Treatments Using Serial CT Angiography) study is a multicenter prospective cohort study at 12 centers in Canada, South Korea, Spain, the Czech Republic, and Turkey. First enrollment was in March 2010 and final follow-up occurred in March 2016.
Dr. Demchuk and colleagues examined demographics, clinical characteristics, time from alteplase to recanalization, and intracranial thrombus characteristics for 575 patients with acute ischemic stroke and intracranial arterial occlusion demonstrated on computed tomographic angiography (CTA).
All patients underwent a head and neck CTA at baseline and repeat head CTA four hours later. The researchers assessed the extent of intracranial thrombus using the clot burden score (a score of 0 implies complete occlusion of the ipsilateral anterior circulation vessels; a score of 10 implies no occlusion). Permeability of intracranial thrombus was assessed using the residual flow grade.
The primary outcome was successful recanalization defined as a revised arterial occlusion scale score of 2b or 3 on repeat CTA or conventional cerebral angiogram obtained within six hours of initial CTA.
Of the 575 patients in the cohort, 275 patients (47.8 percent) received intravenous alteplase only, 195 (33.9 percent) received intravenous alteplase plus endovascular thrombectomy, 48 (8.3 percent) received endovascular thrombectomy alone, and 57 (9.9 percent) received conservative treatment.
Successful recanalization occurred in 157 patients (27.3 percent) overall, including in 143 (30.4 percent) of those who received intravenous alteplase and 14 (13.3 percent) who did not.
Dr. Demchuk noted that the findings suggest recanalization with intravenous alteplase is a continuous process over time. “tPA has a short half-life, but one of the surprising findings is that we saw recanalization even at later points after tPA has supposedly become inactive,” he said. “We believe the clot is softened by the tPA and starting to break up, but the process continues with natural lysis over many hours.”
Also intriguing is the finding that recanalization is associated with increased porosity, suggesting that with highly permeable clots the tPA has more surface area to work on, Dr. Demchuk said.
More generally, he said the success rate of tPA should be encouraging to clinicians. “tPA works,” he told Neurology Today. “We do have a cohort in this study for whom it is contraindicated. But the between-group recanalization rates are quite remarkable. Clinicians are sometimes hesitant to use tPA because it does have risks, but I believe these results should provide some comfort.”
Finally, Dr. Demchuk said he hopes information from the study can inform clinical trials of other agents, or adjuncts to tPA, that can lead to improvements in clinical outcome for patients with stroke.
Experts who reviewed the report for Neurology Today agreed the study is a strong one that provides important information about which patients should and should not be considered for tPA.
“This international multicenter study is very important because it investigated how intravenous alteplase treatment and thrombus characteristics are associated with clinical outcomes in patients with acute ischemic stroke,” said Bart M. Demaerschalk, MD, MSc, professor of neurology at Mayo Clinic in Phoenix, AZ.
“This study is helpful in designing the EMS transport plans for regional stroke systems of care and in deciding whether to transport patients with acute ischemic stroke to a thrombectomy-capable stroke center or comprehensive stroke center for endovascular therapy.”
Dr. Demaerschalk added: “In the event that transport times from the field are a few hours longer to a comprehensive stroke center compared with an acute stroke-ready hospital or a primary stroke center, evaluation at a telemedicine-enabled acute stroke hospital, for instance, or at a primary stroke center for initial treatment with intravenous alteplase is likely the better option based on reasonable recanalization rates with alteplase over several hours.”
“The study also points to a clear need to predict with clinical and imaging criteria which patients are most suitable for transfer to stroke centers capable of endovascular therapy versus who can remain at a local community stroke center,” he said.
Tudor G. Jovin, MD, professor of neurology at the University of Pittsburgh, agreed. “This topic has become more important with the advent of thrombectomy because it has implications with regard to which patients should be routed directly to an endovascular center and which should go first to a closer primary care center to receive tPA,” Dr. Jovin said. “One of the biggest issues in stroke care today is how to build a system of care that can appropriately triage patients.”
Dr. Jovin, who is also director of the University of Pittsburgh Medical Center Stroke Institute and the UPMC Center for Neuroendovascular Therapy, said: “The authors of the study are to be congratulated for a strong study. One of the limitations is that the decision regarding the most appropriate delivery site should ideally be made in the pre-hospital setting. With the advent of mobile stroke units in ambulances, the kind of information the study provides would be very useful. But whether mobile stroke units will be standard and widely used remains to be seen.”
Another approach would be to determine if certain clinical measures that can be ascertained in the ambulance can be correlated with successful recanalization with either tPA or thrombectomy. Dr. Jovin said he is among investigators leading a randomized trial to look at that question in Catalonia, Spain, using the Rapid Arterial Occlusion Evaluation Scale.