Thrombolytic therapy delivered intra-arterially within 3 hours of stroke onset appears to improve recanalization rates compared with the same agents given intravenously, according to recent study data
in Neurosurgery (2004;54:39-46). Recanalization rates are associated with better outcomes in stroke, said the study’s lead investigator Eric C. Bourekas, MD, assistant professor of radiology at The Ohio State University in Columbus, but intra-arterial (IA) delivery of thrombo-lytic drugs is more complex than
the standard intravenous (IV) route and requires specialized stroke teams that must be available around the clock.
In 1995, the National Institute of Neurological Disorders and Stroke (NINDS) study group showed in
a double-blind, placebo-controlled trial that IV recombinant tissue plasminogen activator (rt-PA) administered within 3 hours of stroke onset reduced disability with no effect on mortality despite an increase in symptomatic intracerebral hemorrhage. In the meantime, noncontrolled studies have suggested that IA thrombolysis could improve recanalization rates.
Led by Dr. Bourekas, researchers analyzed the results of early IA thrombolytic treatment with either rt-PA or urokinase in 36 patients with acute ischemic stroke, all of whom were treated within 3 hours of symptom onset. The average time to treatment was 1 hour 46 minutes. Overall, artery recanalization occurred in 75% of the patients, and complete recanalization occurred in 39%. These recanalization rates are about twice as high as those achieved with IV thrombolytic therapy of acute ischemic stroke.
The improved recanalization rates appear to lead to better outcomes, according to Dr. Bourekas. One to 3 months after IA treatment, 50% of patients had little or no disability resulting from their stroke, as determined by scores on the modified Rankin Scale. The outcomes were similar regardless of whether rt-PA or urokinase was administered, although the overall recanalization rate was greater with urokinase and the complete recanalization rate was greater with rt-PA. By comparison, only 39% of patients treated with early IV thrombolytic therapy in the NINDS trial had little or no disability at 1 to 3 months.
The rate of symptomatic intracranial hemorrhage was 11% with IA treatment, compared with 6.4% with IV rt-PA in NINDS. Mortality was 22% in patients receiving IA therapy, similar to that with IV therapy (17%).
IA thrombolysis allows for a higher concentration of thrombolytic agent in the vicinity of the clot compared with IV treatment, with the main advantage being superior recanalization; however, there are many drawbacks to administering this therapy. “It does require facilities and trained personnel, including neuroradiologists, who frequently are not available at many hospitals,” said Dr. Bourekas. “Dedicated teams are essential and involve neurologists, neuroradiologists, emergency physicians, nurses, and angiography technologists, to name a few, representing more personnel than are required for IV treatment.” Treatment times are generally longer for IA thrombolysis versus IV thrombolysis, but “IA therapy is feasible within 3 hours
of symptom onset if a dedicated stroke team is available 24 hours
a day,” he said.
In addition, IA thrombolysis requires a more invasive procedure with the risks of angiography and catheterization of intracranial vessels. However, in one large controlled trial of IA thrombolytic therapy called the Prolyse in Acute Cerebral Thromboembolism II, no direct microcatheter-related com-plications were reported. In the current analysis of 36 patients, there was only one such complication, which did not cause neurologic deterioration.