KISSIMMEE, FLA. — A combination of intravenous and intraarterial thrombolysis significantly improved outcomes in stroke patients whose clots did not clear with initial thrombolytic therapy, Dr. Joseph Broderick reported at the 31st International Stroke Conference.
“We already know that tissue plasminogen activator (TPA) is an effective drug, but it doesn't open the artery in every patient,” Dr. Broderick, chairman of the neurology department at the University of Cincinnati, said in an interview. “We need another way to help these people.”
The Interventional Management of Stroke Study-II (IMS-II) included 73 patients with severe stroke (median National Institutes of Health Stroke Scale score of 19). All received an initial course of low-dose intravenous TPA within the first 3 hours of stroke onset (median time 41 minutes).
The initial thrombolysis cleared the clot in 22 patients, none of whom received further therapy. The remaining 51 patients, however, still had a clot blocking an artery in either the neck or the head.
Those patients were treated with an additional dose of TPA (maximum 22 mg). In 33 patients, the drug was delivered directly to the clot by an infusion catheter equipped with a low-dose ultrasound transducer at the distal tip. The ultrasound energy creates microfractures in the clot, which enables the better delivery of the thrombolytic agent.
The remaining 18 patients received the additional therapy with a standard catheter.
Dr. Broderick compared outcomes in the 51 patients who received the intraarterial therapy with those of patients matched for age and stroke severity who received intravenous recombinant TPA in a 1995 study called the National Institute of Neurological Disorders and Stroke (NINDS) rtPA [recombinant tissue-type plasminogen activator] Stroke Study Group (N. Engl. J. Med. 1995;333:1581–8).
The patients in the IMS-II study had significantly lower mortality at 3 months (16% vs. 21%), and more of them had a Rankin score of 0–2 at 3 months (45% vs. 39%; odds ratio 1.65), compared with the NINDS study patients.
Symptomatic intracranial bleeds occurred more frequently in the IMS-II group than in the NINDS group (11% vs. 6.6%), as did asymptomatic bleeds (29% vs. 6%). This is not surprising, given that the invasive nature of the second course of TPA, Dr. Broderick said at the conference, which was sponsored by the American Stroke Association.
The increased risk of bleeding indicates that intraarterial therapy should be reserved for those patients with severe stroke. Older patients should be carefully evaluated before receiving the treatment, he warned.
The IMS-II trial didn't distinguish the effect of the interventional device versus the thrombolytic drug, Dr. Broderick noted. “We weren't testing an individual device; we were testing a therapeutic approach.”
A third IMS trial, sponsored by NINDS, is designed to evaluate the combined thrombolytic approach using a number of different devices. Physicians will be allowed to use any FDA-approved clot removal device; if additional devices are approved during the course of the trial, they will be allowed.
The treatment advantage of this trial design is clear, Dr. Broderick noted.
“There's no one choice that is good for all clots. Physicians will get to choose the right tool for the job. The important thing is to maximize the quickest possible opening of the blocked artery,” he said.
He hopes to include 50 centers and 900 patients in the new trial.
'The important thing is to maximize the quickest possible opening of the blocked artery.' DR. BRODERICK