Thrombolytic Therapy With Streptokinase in Acute Ischemic Stroke - MAST-E


The Multicenter Acute Stroke Trial-Europe (MAST-E) was a multicenter, prospective, double-blind, controlled trial designed to assess the efficacy and safety of streptokinase in patients with acute ischemic stroke. Follow-up was six months.


Streptokinase would reduce the rate of severe neurologic disability and mortality in patients with acute ischemic stroke.

Study Design

Study Design:

Patients Screened: N/A
Patients Enrolled: 310
NYHA Class: N/A
Mean Follow Up: Six months
Mean Patient Age: 22-94
Female: 43
Mean Ejection Fraction: N/A

Patient Populations:

All patients who were hospitalized because of the sudden onset of a focal neurologic deficit attributable to ischemia in the territory of the middle cerebral artery and who could be randomly assigned to a treatment group within six hours after the onset of symptoms were eligible for enrollment.


The criteria for exclusion were a mild deficit (MAST score >55), the resolution of symptoms before randomization, a computed tomographic scan showing cerebral hemorrhage or a nonvascular disorder, a previous hemorrhagic stroke or a previous stroke with clinical sequelae, recent surgery or trauma, another illness known to compromise prognosis, or known or suspected pregnancy.

Primary Endpoints:

The primary efficacy outcome was a binary criterion combining mortality with severe disability at six months, with severe disability defined as a score of 3 or higher on the Rankin scale. The primary safety outcomes were mortality at 10 days and cerebral hemorrhage.

Secondary Endpoints:

The secondary efficacy outcomes were death, recurrent cerebrovascular events, and ischemic events.

Drug/Procedures Used:

Patients with moderate to severe ischemia in the territory of the middle cerebral artery were randomly assigned to receive streptokinase (1.5 million units over a period of one hour) or placebo within six hours after the onset of stroke.

Concomitant Medications:

The use of concomitant treatments was left to the discretion of the participating investigators. Sixty-five percent of the patients in the streptokinase group and 75% in the placebo group received concomitant treatment with heparin.

Principal Findings:

A total of 310 patients were enrolled (156 in the streptokinase group and 154 in the placebo group) and all of them were evaluated at six months. The incidence of the primary efficacy outcome (a binary criterion combining mortality and severe disability at six months) was similar in the two groups (124 patients in the streptokinase group and 126 in the placebo group died or had a Rankin score ≥3).

The mortality rate at 10 days was significantly higher in the streptokinase group than in the placebo group (34% vs. 18.2%, p=0.002). The higher mortality rate in the streptokinase group was mainly due to the hemorrhagic transformation of ischemic cerebral infarcts (symptomatic cerebral hemorrhage 21.2% in the streptokinase group vs. 2.6% in the placebo group, p<0.001).


Among patients with acute ischemic stroke, treatment with streptokinase was associated with no difference in the primary endpoint, but was associated with an increase in mortality. The routine use of streptokinase cannot be recommended in acute ischemic stroke.


Thrombolytic therapy with streptokinase in acute ischemic stroke. The Multicenter Acute Stroke Trial—Europe Study Group. N Engl J Med 1996;335:145-50.

Keywords: Middle Cerebral Artery, Stroke, Follow-Up Studies, Streptokinase, Fibrinolytic Agents, Cerebral Hemorrhage

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