What is the role of heparin (unfractionated heparin) in the treatment of ischemic stroke?

Heparin in Ischemic Stroke: Current Recommendations

Urgent anticoagulation with heparin is not recommended for the treatment of acute ischemic stroke as it does not improve neurological outcomes or prevent early recurrent stroke, while significantly increasing the risk of bleeding complications. 1

Evidence Against Routine Heparin Use

The evidence consistently shows that early administration of heparin in acute ischemic stroke:

• Increases risk of symptomatic hemorrhagic transformation, especially in severe strokes 2, 1
• Does not lower the risk of early recurrent stroke, even in cardioembolic stroke 2
• Does not improve neurological outcomes or prevent early neurological worsening 2, 1
• Increases risk of serious bleeding complications in other parts of the body 2

A comprehensive individual patient data meta-analysis of the five largest randomized controlled trials comparing heparins with aspirin or placebo found no evidence that patients at higher risk of thrombotic events or lower risk of hemorrhagic events benefited from heparin treatment 3.

Limited Potential Applications

While routine use is not recommended, heparin may be considered in highly specific clinical scenarios:

• Patients with symptomatic large artery stenosis >70% 1, 4
• Non-occlusive intraluminal thrombus 4, 5
• High-risk cardiac conditions including:
  • Left ventricular thrombus
  • Left ventricular assist devices
  • Mechanical heart valves 4

A small case series of 18 patients with non-occlusive intraluminal thrombus treated with intravenous heparin showed complete or partial lysis of thrombus without intracranial hemorrhage 5. However, this limited evidence is insufficient to override guideline recommendations.

Recommended Antithrombotic Approach

Instead of heparin, guidelines recommend:

• Aspirin (75-100 mg daily) as the primary antithrombotic for secondary stroke prevention 1
• Administration of aspirin within 24-48 hours after stroke onset (loading dose 160-325 mg) 1
• For DVT prophylaxis only: Low-dose subcutaneous unfractionated heparin or LMWH may be considered in high-risk patients 1

Common Pitfalls to Avoid

1. Using heparin with the expectation of improving neurological outcomes or preventing early recurrence
2. Administering heparin after thrombolytic therapy without sufficient evidence of safety
3. Failing to monitor anticoagulation levels if heparin is used in select high-risk patients
4. Using heparin as a substitute for proven interventions like IV alteplase or mechanical thrombectomy

Monitoring Considerations

If heparin is used in the limited scenarios described above:

• Close monitoring of anticoagulation levels is essential
• Dosage adjustments should be made based on levels to improve safety 2
• Careful assessment of bleeding risk should be performed before initiation

The International Stroke Trial, one of the largest randomized clinical trials of heparin in acute stroke, demonstrated significant excess in bleeding complications without clinical benefit at 6 months 6, further supporting the recommendation against routine heparin use in acute ischemic stroke.