With urokinase rapidly fading into fond memory, interventionalists are slowly sorting out dosing for its alternatives -- alteplase and reteplase -- for clearing occlusions and treating stroke.
The performance of the three drugs in clearing peripheral arterial occlusions is nearly indistinguishable, according to Dr. Kenneth Ouriel of the Cleveland Clinic. Data on 472 patients in the Retrospective Evaluation of Thrombolytic Reperfusion of Occlusions Study showed a 78% to 84% clinical success rate among the three drugs and 81% to 90% successful clot lysis.
Neither range was statistically significant, nor were comparisons of rethrombosis, major bleeding, or intracranial bleeding. Tested at both low and high doses, all three drugs had comparable safety profiles. The performance of urokinase, however, was significantly improved when heparin was added.
Strictly on a cost basis, the results favor alteplase, said Ouriel, who presented the data at the SCVIR meeting in San Antonio on Monday. The departed urokinase averaged $4343 per patient, compared with $820 for alteplase and $1441 for reteplase.
"In experienced hands, all the options are safe and effective," he said. "Cost will be a major factor, and we'll need to address the economic impact of complications."
A number of studies discussed at the meeting focused on sorting out appropriate doses, particularly for reteplase. Focusing on lower extremity thrombosis, University of Illinois researchers compared three doses (0.5, 0.25, and 0.125 units per hour) in 80 patients. Success rates ranged from 82% to 94%, with no significant differences. Total infusion time was roughly the same for the larger two doses, at about 30 hours, but jumped to 42 hours for the smallest dose. More than 13% of high-dose patients had bleeding complications, however, compared with about 6% for the medium- and low-dose patients.
"At this point, all groups are very similar in terms of success, but the high-dose complications and the longer infusion time for the low-dose group will lead us to use 0.25 at our institution once the trial is completed," Dr. Flavio Castaneda said.
Reteplase is gaining favor over alteplase because it can be diluted without loss of activity or precipitation, said Dr. John Barr of the Cleveland Clinic. Barr reported on off-label use of reteplase as an intra-arterial treatment for acute stroke.
In nine patients seen 30 minutes to more than six hours after onset of stroke symptoms, Barr and colleagues used one to four units of reteplase, starting with a 0.5- to 1-unit bolus and following with infusion at 1 unit per hour. The therapy was combined with a 2000-unit bolus of heparin and a 500-unit per hour heparin infusion.
The technique achieved revascularization in eight of nine patients, with one dying of an unrelated infarct. Six patients showed considerable neurological improvement. One required manual snaring of a well-organized thrombus via endovascular embolectomy.
"The results are preliminary and limited, but they're encouraging," Barr said. "Using heparin appears safe, but we don't know if it's necessary. As data are added to the INSTOR stroke registry, we'll learn more."
-- Jane Lowers
For more about the INSTOR stroke registry:
Interventional stroke registry hopes to set up emergency treatment protocols (Nov. 2, 2000) http://www.diagnosticimaging.com/db_area/onlinenews/2000/2000110201.shtml
