Why was streptokinase not used in ischemic stroke?

In the early 1980s, there is a surge in the interest of using streptokinase in the treatment of pulmonary embolism and myocardial infarction. Both is found to be effective [ref1][ref2][ref3]. Hence, this interest is transferred to recanalization of ischemic stroke.

Three large multicenter randomized trial, Australian Streptokinase Trial (ASK), Multicenter Acute Stroke Trial-Europe (MAST-E), and Multicenter Acute Stroke Trial-Italy (MAST-I) was conducted with objective to evaluate the safety and efficacy of IV Streptokinase alone or in combination with aspirin or heparin. These studies however, were stopped prematurely because of high amount of mortality in the thrombolysis treated group. [ref4][ref5][ref6][ref7][ref8]. The higher rate of mortality in this group was mainly due to the hemorrhagic transformation of ischemic cerebral infarcts [ref5]. Dues to this reason, streptokinase has became a “nightmare” of thrombolytic therapy in ischemic stroke.

It is not know exactly why this could happened. One of the reasons suggested for such misfortune is that the dosage used is similar with that of myocardial infarction which is 1.5 million unit for which may be high for treating ischemic stroke. Others has stated that it was probably as the result of combination of aspirin or heparin usage. [ref9]


1. R.G Gonzalez et al. Acute ischemic stroke: imaging and intervention. Second edition. Springer, New York, NY. 2011.
2. Marder V.J. and S. Sherry. Thrombolytic therapy: current status (1). New England Journal Med of Medicine. 1988; 318(23): 1512–1520.
3. Marder V.J. and S. Sherry. Thrombolytic therapy: current status (2). New England Journal of Medicine. 1988; 318(24): 1585–1595
4. Yasaka M. et al. Streptokinase in acute stroke: effect on reperfusion and recanalization. Australian Streptokinase Trial Study Group. Neurology. 1998; 50(3): 626–632.
5. Thrombolytic therapy with streptokinase in acute ischemic stroke. The Multicenter Acute Stroke Trial–Europe Study Group. New England Journal of Medicine. 1996; 335(3):145–150.
6. Geoffrey A.D et al. Streptokinase for Acute Ischemic Stroke With Relationship to Time of Administration. JAMA. 1996; 276(12): 961-966.
7. Randomised controlled trial of streptokinase, aspirin, and combination of both in treatment of acute ischaemic stroke. Multicentre Acute Stroke Trial–Italy (MAST-I) Group. Lancet. 1995; 346(8989): 1509–1514.
8. C. Cornu et al. Streptokinase in Acute Ischemic Stroke: An Individual Patient Data Meta-Analysis. Stroke. 2000; 31: 1555-1560
9. Assia Jaillard et al. Hemorrhagic Transformation in Acute Ischemic Stroke : The MAST-E Study. Stroke. 1999; 30:1326-1332


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