Combining Clot-Buster Drug with Clot-Busting Device Can Open Blood Vessels in High-Risk Stroke Patients

BUFFALO, N.Y. -- A novel approach to treating high-risk stroke patients who were poor candidates for traditional clot-busting therapy enabled one-third of patients in a prospective trial, all of whom otherwise would be expected to suffer severe deficits, to return to functional independence, neurosurgeons at the University at Buffalo report.

Results of the trial appear in the November issue of Neurosurgery.

A group headed by Adnan Qureshi, M.D., UB associate professor of neurosurgery, devised a treatment for these high-risk patients that combined injection of a low dose of a third-generation tissue-plasminogen activator (tPA) -- a longer-acting clot dissolver than standard tPA -- with balloon angioplasty or a snare device to break up the clot, increasing the drug's effectiveness.

The UB group is one of the first to test this approach in a prospective trial.

Of the 19 patients studied -- none of whom were appropriate candidates for standard intravenous tPA therapy -- seven were able to perform activities of daily living independently at follow-up.

"This trial opens up a new horizon for stroke treatment," Qureshi said. "It shows the feasibility of using both measures together in opening up the blood vessels and reducing the risk of hemorrhage. The two mechanisms work synergistically. None of the 19 patients experienced symptoms of brain hemorrhage.

"Almost all of these patients would be expected to do really poorly," he said. "More than one-third now are able to live with good functional capacity."

Ten patients did not survive the one-to-three-month follow-up period because of the severity of their initial stroke. One patient died soon after treatment, six died of a massive second stroke, one of a heart attack and three of complications of pneumonia. Two patients developed disability related to the stroke.

The biggest problem in stroke treatment today, Qureshi said, is finding a way to open up blocked vessels quickly without causing hemorrhage. All thrombolytic agents, when administered intravenously at recommended levels, may cause bleeding in the brain by virtue of their blood-thinning action. The risk is dose-dependent: Lowering the drug dose lowers the likelihood of hemorrhage, but it also decreases the drug's clot-dissolving effectiveness.

Thrombolytics such as the standard tPA have other limitations, as well. They must be administered within three hours of stroke-onset to be effective, they are active for only six-to-10 minutes and they aren't recommended for patients who have had a recent surgery. Another stroke treatment option -- using mechanical devices alone, such as balloon angioplasty or snares, to break up a clot without the drug -- increases the chances that clot fragments will block another vessel downstream.

"These problems prompted us to look for alternate treatments," Qureshi said.

The researchers settled on a newer, longer-acting clot-dissolving agent called reteplase, which they injected in small doses directly into the clot through a catheter, rather than through an IV line. If the drug alone didn't reopen the vessel quickly, the endovascular physicians broke up the clot mechanically, enabling the drug to work more effectively. (Clot-dissolving drugs can penetrate only the surface of a clot; breaking up the clot into pieces allows the drug to penetrate more deeply.)

All surgeries took place at Millard Fillmore Hospital of Kaleida Health, the UB department's primary clinical site.

"The biggest fear in stroke treatment," Qureshi said, "is that the situation can be made worse. In this pilot study, none of the patients experienced damaging hemorrhages. Unfortunately, some patients received no benefit. But seven out of 19 were alive and living independently at follow-up. Given the selection of patients, this is an impressive result."

The next step is to conduct a larger study of the combined therapy, he said.

Also contributing to the study, all from the Department of Neurosurgery and the Toshiba Stroke Research Center in the UB School of Medicine and Biomedical Sciences, were Amir M. Siddiqui, M.D.; M. Fareed K. Suri, M.D.; Stanley H. Kim, M.D.; Zulfiqar Ali, M.D.; Abutaher M. Yahia, M.D.; Alan S. Boulos, M.D.; Mustafa Saad, M.D.; Lee R. Guterman, Ph.D., M.D., and L. Nelson Hopkins, M.D.

Also contributing were Demetrius K. Lopes, M.D, of Rush-Presbyterian-St Luke's Hospital in Chicago, and Andrew J. Ringer, M.D., of the University of Cincinnati.