Another Promising New Antistroke Treatment

abstract & commentary

Synopsis: These data from the PROACT study suggest that intra-arterial r-proUK may extend this therapeutic window for acute ischemic stroke to six hours.

Source: Furlan A, et al. JAMA 1999;282:2003-2011.

Thrombolysis with intravenous tissue plasminogen activator (tPA) has been shown to be beneficial when given within three hours of acute ischemic stroke. These data from the PROACT study suggest that intra-arterial (IA) recombinant prourokinase (r-proUK) may extend this therapeutic window to six hours.

A total of 180 patients were randomized in a ratio of 2:1 to receive up to 9 mg of IA r-proUK plus heparin (n = 121) or heparin only (n = 59). In the primary analysis, 40% of r-proUK patients and 25% of control patients had a modified Rankin score of 2 or less (P = 0.04). This was a 58% relative benefit. Recanalization rates were 66% for the r-proUK group and 18% for the control group (P < 0.001). Other secondary outcome measures at 90 days, such as Barthel Index of 90 or more or NIH Stroke Scale of 1 or less showed insignificant trends toward benefit. The overall hemorrhage rate was 35% with r-proUK compared to 13% in controls, while symptomatic hemorrhage occurred in 10% and 2%, respectively. There were no differences in mortality.

Comment by alan z. segal, MD

Although total hemorrhage rates were high for r-proUK (often small and seen on a mandatory post-procedure CT scan), the symptomatic rate was only 10%. This is not enormously higher than in the NINDS-tPA trial (6.3%). Furthermore, the r-proUK patients were treated later and had larger strokes, both factors known to increase hemorrhage risk.

IA thrombolysis should be strongly considered for patients presenting with MCA occlusion within 3-6 hours of symptom onset. IA therapy for basilar artery occlusion might be considered up to 12 hours post-stroke. In the 0- to 3-hour time window, IV tPA remains the standard of care. However, in centers where it is available, combination IV followed by IA therapy should be considered.

r-proUK is not currently FDA approved. Current options for IA therapy include nonrecombinant urokinase (which is currently out of production) or tPA (which may be given in IA doses of approximately 20-30 mg). (Dr. Segal is Assistant Professor, Department of Neurology, Weill-Cornell Medical College, Attending Neurologist, New York Hospital.)