Jun 21 2004
A small Ohio study has offered the first published evidence that aggressively treating brain blood clots at their source soon after symptoms start can produce a good outcome for many stroke patients.
In the study, published in a recent issue of the journal Neurosurgery, 50 percent of stroke patients had little or no neurological disability one to three months after clot-dissolving medication was delivered directly to the site of the blockages, compared to 39 percent of patients with similarly good outcomes documented in a large national trial of intravenous (IV) drug treatment for stroke. In all cases, time was an issue: The drugs in both trials were administered within three hours of the onset of symptoms.
“The results tell us what many of us suspected – that targeting the problem and delivering drugs right to the problem is a better option for appropriate stroke patients,” said Eric Bourekas, an interventional neuroradiologist at Ohio State University Medical Center and lead author of the study.
Researchers at OSU Medical Center and Case Western Reserve University compared patient outcomes from their institutions to the outcomes reported in 1995 after a study led by the National Institute of Neurological Disorders and Stroke. In that large trial, patients who were treated intravenously with recombinant tissue plasminogen activator (rt-PA) within three hours of symptom onset were at least 30 percent more likely to have good outcomes compared to patients on placebo. That study led to the intravenous use of rt-PA as the only federally approved clot-dissolving treatment of ischemic stroke – the roughly 80 percent of strokes caused by blockage of a blood vessel.
The two Ohio centers treated hundreds of stroke patients using the intra-arterial (IA) method of drug delivery over the time period observed, between 1993 and 2002, but only 36 patients received the medication within three hours after symptoms began, matching the conditions of therapy measured in the NINDS trial. These patients also had the same median admission score – based on a common stroke severity analysis tool – as the NINDS patients.
The intra-arterial treatment involves first obtaining X-rays of the affected blood vessels, or angiograms, by introducing a contrast agent to the bloodstream. Once the blockage is identified, physicians insert a catheter in the leg that is guided through the neck to the brain and the site of the clot. Physicians at OSU and CWRU used a different clot-dissolving agent, urokinase, until it became unavailable in the United States, and then began using rt-PA, the approved drug for IV use in stroke patients. Physicians stopped administering the drug either once the vessel completely opened or when the maximum drug dose was reached.
“Based on its symptoms, stroke can look like something else, so an advantage of the IA therapy is that we are much more clear about what we’re treating. We study the blood vessels, we see the clot, we know we’re treating a stroke, and the level of confidence is much higher,” Bourekas said. “We also may use less of the drug, which may reduce the risk of hemorrhage, because we can watch the clot dissolve and stop administering the drug as soon as the vessel opens up.”
The biggest advantage demonstrated by the study is that administering drugs at the clot site rather than through an IV is more likely to reopen the vessel, considered a major contributor to improved stroke outcomes. Partial or complete recanalization occurred in 75 percent of the patients treated with IA therapy at OSU and Case Western, compared to the 20 percent-to-50 percent range of recanalization in most IV treatment trials, said Andrew Slivka, a study co-author, neurologist and director of OSU Medical Center’s stroke division.
The rates of patient deaths and symptomatic hemorrhages were comparable to rates in other stroke studies, and tended to be associated strongly with much more severe strokes rather than treatment method. Angiography and catheterization of blood vessels in the head do carry risks, but the Ohio study resulted in only one catheterization-related complication that did not cause neurological damage, the researchers said.
Having a 24-hour stroke treatment center is required to achieve the best results with the intra-arterial therapy, the Ohio State researchers noted. “A team of radiologists and neurologists must be available around the clock and be ready for that rapid response,” Slivka said. “When blood flow to the brain is compromised, the brain won’t tolerate it for very long. Time is critical. The faster we can dissolve the clot to re-establish blood flow to that part of the brain, the more likely we are to have a good result.”
Patients’ realization that they’re having a stroke and their ability to get to a hospital are major variables, as well. Major stroke symptoms include a sudden inability to move a leg or arm, slurred speech or being unable to talk, sudden blindness, a sudden headache or numbness throughout one side of the body.
Finally, the researchers acknowledge they cannot recommend IA therapy across the board given the small size of their study. Bourekas said a larger study is needed to prove that “clot-busting” at the stroke site offers better chances for a good stroke outcome than IV therapy, and said researchers are hopeful a large, federal trial will be done to further test the therapy’s effectiveness.
Additional study co-authors were Rajul Shah of OSU Medical Center and Robert Tarr, Jeffrey Sunshine and Jose Suarez of the University Hospitals of Cleveland and CWRU.