Giving Clot Busters in Arteries Has Some Benefits

Injecting clot-busting drugs into an artery after stroke nearly doubled the rate of favorable outcomes and nearly halved the number of deaths compared to people who didn't get the drugs. However, it also increased the risk of bleeding, researchers report in today's rapid access issue of Stroke: Journal of the American Heart Association.

Typically, clot-busting drugs, called thrombolytics, are injected through a vein (intravenously). This analysis reviewed studies of intra-arterial thrombolytics (IAT), which is delivering clot busters via an artery.

Researchers reviewed of 27 studies from 1988 to 2002 comprising 852 stroke patients who received IAT and 100 who did not receive thombolytics. They found that IAT led to favorable outcomes in 41.5 percent of patients, compared to 23 percent patients who didn't receive thrombolytics. The death rate was also lower among patients given IAT -- 27.2 percent vs. 40 percent. A subset of patients who received both intra-arterial and intravenous thrombolytics did even better, as 53.6 percent had favorable outcomes.

For the purposes of the study, the researchers defined a favorable outcome as the absence of significant disability. In most of the studies, neurologic outcomes were evaluated 90 days after the stroke.

Bleeding in the brain occurred more often in the IAT patients than the controls -- 9.5 percent vs. 3 percent. However, the increased bleeding did not translate into increased death rate.

The higher rate of bleeding may be a reflection of stroke severity because bleeding tends to occur in patients with more severe strokes, researchers say.

"There appears to be a net benefit from intra-arterial thrombolytic therapy," says Mark J. Alberts, M.D., professor of neurology and director of the stroke program at Northwestern University in Chicago. "However, the benefit comes at a cost in the form of an increased rate of symptomatic intracerebral hemorrhage, which needs to be kept in mind when considering this type of therapy."

The computerized database search revealed that most patients received the thrombolytic drug urokinase, which only resumed availability in the United States last month. Other thrombolytics used were prouokinase, streptokinase and plasminogen activator (tPA).

In 1996, tPA became the only U.S. Food and Drug Administration-approved treatment for acute stroke, but it must be given within three hours of symptom onset. The three-hour time window has limited the use of tPA in stroke patients, and some studies have indicated that only 2 percent to 3 percent of stroke patients actually receive the drug, Alberts says.

Intra-arterial delivery of tPA has some theoretical advantages, he says. The drug can be delivered directly to the clot, whereas intravenous administration requires the drug to pass through the heart before entering the arterial circulation. A higher dose could be carried directly to the clot by an artery.

Those factors might expand the treatment window beyond three hours. The only large, controlled study of intra-arterial therapy for acute stroke showed that patients benefited from thrombolytics when treated up to six hours after stroke onset.

Intra-arterial therapy also reduces or eliminates the risk of giving clot busters to a patient who does not have a clot. The treatment requires an angiogram, which allows the physician to look inside the artery and confirm that a clot is present before injecting the drug, Alberts explains. Intravenous therapy is performed without angiography, creating a potential risk of giving tPA to patients who do not have clots.

The disadvantages of arterial therapy relate to the time and resources required. In particular, many hospitals do not have facilities to perform angiography on an emergency basis, says Alberts.

The outcomes in this analysis were better than previous studies, researchers say.

Several ongoing studies are evaluating the safety and effectiveness of intra-arterial tPA in stroke patients. Additionally, the clot-dissolving drug urokinase has just returned to the U.S. health market after several years, and the renewed availability of the drug could lead to other evaluations of intra-arterial therapy, Alberts says.

"The fact that the agent will be available again might be a good thing, since it is the drug that physicians have used most often for intra-arterial thrombolytic therapy," he says.

Co-authors of the study were Rejane C. Lisboa, M.D., and Borko D. Jovanovic, Ph.D.