What is the recommended dose of streptokinase for acute ischemic stroke?

Streptokinase Is Not Recommended for Acute Ischemic Stroke

Streptokinase should not be used for the treatment of acute ischemic stroke due to increased mortality and hemorrhagic complications. 1 Clinical trials using streptokinase at a dose of 1.5 million units were halted prematurely because of unacceptably high rates of hemorrhage and mortality.

Evidence Against Streptokinase Use

Clinical Trials and Safety Concerns

• Three major trials of streptokinase in acute ischemic stroke were terminated early due to:

  • Excess mortality and poor outcomes in treated patients (Level I evidence) 1
  • Significantly higher 10-day mortality rate (34.0% vs 18.2%, p=0.002) 2
  • Increased risk of hemorrhagic transformation of ischemic cerebral infarcts 2

• The dose used in these trials was 1.5 million units administered over one hour, which is the same dose used for myocardial infarction but may have been too high for stroke patients 1

• Treatment was initiated up to 6 hours after symptom onset in these trials, which may have contributed to the poor outcomes 1

Specific Risks

• When combined with aspirin, streptokinase showed even worse outcomes:
  • Significantly increased early case fatality from day 3-10 (OR 2.1; CI 1.2-3.6) 3
  • Higher rate of cerebral hemorrhagic complications (OR 2.0; CI 1.3-3.7) 3

Current Recommended Thrombolytic Therapy

The only FDA-approved thrombolytic therapy for acute ischemic stroke is recombinant tissue plasminogen activator (rtPA):

• Recommended dosing for rtPA: 0.9 mg/kg (maximum dose 90 mg) administered intravenously with 10% given as bolus over 1 minute and the remainder infused over 60 minutes 1

• Treatment must be initiated within 3 hours of symptom onset (Grade A recommendation) 1

• Some guidelines suggest rtPA may be considered within 4.5 hours but not within 3 hours of symptom onset (Grade 2C) 1

Alternative Thrombolytic Agents

Other thrombolytic agents that have been investigated:

• Tenecteplase: Shows promise with greater reperfusion and major vessel recanalization with fewer bleeding complications than alteplase in pilot studies 1

• Desmoteplase: Derived from vampire bat saliva, has shown encouraging safety data in penumbral imaging-selected patients up to 9 hours after stroke onset, though phase III studies are ongoing 1

• Ancrod: A defibrinogenating agent derived from snake venom, has been investigated but with limited evidence of benefit 1

Important Monitoring and Management Considerations

For patients receiving thrombolytic therapy:

• Admit to intensive care or stroke unit for monitoring 1
• Perform neurological assessments every 15 minutes during infusion, every 30 minutes for 6 hours, then hourly until 24 hours after treatment 1
• Monitor blood pressure every 15 minutes for 2 hours, then every 30 minutes for 6 hours, then hourly until 24 hours after treatment 1
• Discontinue infusion if patient develops severe headache, acute hypertension, nausea, or vomiting 1
• Delay anticoagulants and antiplatelet agents for 24 hours after treatment 1
• Obtain follow-up CT scan at 24 hours before starting anticoagulants or antiplatelet agents 1

Conclusion

Despite the theoretical benefits of thrombolytic therapy in acute ischemic stroke, streptokinase specifically has been demonstrated to increase mortality and hemorrhagic complications. The American Stroke Association, American Heart Association, and American College of Chest Physicians all recommend against the use of streptokinase for acute ischemic stroke treatment 1.