Desmoteplase After Ischemic Stroke in Patients With Occlusion or High-Grade Stenosis in Major Cerebral Arteries.

Abstract

The beneficial effects of intravenous thrombolysis in ischemic stroke, reperfusion and improved outcome, have been directly correlated to time from onset to treatment. Recanalization of occluded intracranial arteries by tissue-type plasminogen activator (alteplase) has been shown to be effective only for the first few hours after symptom onset. Measured by transcranial Doppler monitoring, the effect of alteplase decreases over time, and treatment delay beyond 4.5 hours predicts lack of recanalization, especially in distal occlusions.1 Will the more fibrin-specific and longer acting fibrinolytics correct this problem in patients admitted beyond the accepted thrombolysis time window of ≤3 to 4.5 hours? A recent report by Albers et al2 provided the outcomes of patients treated with intravenous desmoteplase to reverse occlusion or high-grade stenosis of major cerebral arteries (Desmoteplase in Acute Ischemic Stroke [DIAS]-3 trial) but failed to give support to this idea. This first prospective, randomized, controlled phase 3 trial was designed to detect a possible benefit of a single intravenous bolus of 90 µg/kg of desmoteplase given 3 to 9 hours after onset in patients with confirmed major artery occlusion without substantial ischemic damage.2 Desmoteplase failed to improve functional outcomes at 90 days. It did not increase the rates of symptomatic brain hemorrhage, symptomatic brain edema, and death. On the other hand, significant (nominal P 7 hours after onset of stroke symptoms after a prespecified ordinal analysis.2 In view of a superb safety profile, it should be noted that a previous DIAS-2 trial had tested also a higher dose, 125 µg/kg, in the same time window and observed elevated mortality, albeit predominantly unrelated to the study …