What is the therapeutic window to initiate heparin (anticoagulant) in patients with ischemic (ischaemic) stroke?

From the Guidelines

Heparin is not recommended for acute ischemic stroke treatment, and the decision to start anticoagulation should be based on individual patient risk factors and stroke severity, rather than a specific time window. The use of heparin in acute ischemic stroke has been studied in several trials, including the International Stroke Trial, which found that heparin was effective in lowering the risk of early recurrent stroke, but an increased rate of bleeding complications negated this benefit 1. A more recent guideline from the American Heart Association/American Stroke Association recommends against urgent anticoagulation for treatment of patients with acute ischemic stroke, citing an increased risk of serious intracranial hemorrhagic complications 1.

Key Considerations

• The risk of hemorrhagic transformation of the infarcted area is a major concern when considering anticoagulation with heparin after an ischemic stroke.
• The size of the infarct and risk of hemorrhagic transformation should guide the decision to start anticoagulation, rather than a specific time window.
• For small, non-cardioembolic strokes, anticoagulation may be considered after 24 hours, while for moderate strokes, waiting 3-5 days is advisable, and large strokes may require waiting 7-14 days before initiating anticoagulation.
• Instead of heparin, the standard acute treatment for ischemic stroke includes intravenous thrombolysis with alteplase within 4.5 hours of symptom onset or mechanical thrombectomy within 24 hours for large vessel occlusions.
• For secondary prevention, antiplatelet therapy (aspirin 160-325mg initially, then 81-100mg daily) is typically started within 24-48 hours after stroke onset for non-cardioembolic strokes.

Evidence-Based Recommendations

• Urgent anticoagulation, with the goal of preventing early recurrent stroke, halting neurological worsening, or improving outcomes after acute ischemic stroke, is not recommended for treatment of patients with acute ischemic stroke 1.
• Initiation of anticoagulant therapy within 24 hours of treatment with intravenous rtPA is not recommended 1.
• The usefulness of argatroban or other thrombin inhibitors for treatment of patients with acute ischemic stroke is not well established, and these agents should be used in the setting of clinical trials 1.

From the Research

Ischaemic Stroke Window Period to Start Heparin

• The window period to start heparin in ischemic stroke patients is not clearly defined, but studies suggest that anticoagulation with heparin may be beneficial in certain subpopulations of ischemic stroke patients 2.
• According to a study published in 2015, heparin may be beneficial in patients with symptomatic large artery stenosis >70%, non-occlusive intraluminal thrombus, and in patients with high-risk cardiac conditions including left ventricular thrombus, left ventricular assist devices, and mechanical heart valves 2.
• Another study published in 1994 found that immediate anticoagulation with heparin within 5 hours of onset of first-ever nonlacunar ischemic strokes in the internal carotid artery territories was feasible and generally safe 3.
• However, other studies have shown that the use of heparin in acute ischemic stroke is not recommended due to the risk of bleeding complications and lack of clear benefit 4, 5.
• Low-molecular-weight heparin (LMWH) or dual antiplatelet therapy may be more effective than aspirin alone in preventing early neurological deterioration and improving the 6-month outcome in ischemic stroke patients 6.

Timing of Anticoagulation

• The optimal timing of anticoagulation with heparin in ischemic stroke patients is not well established, but studies suggest that it may be beneficial to start anticoagulation as soon as possible after stroke onset 2, 3.
• However, the decision to start anticoagulation should be made on a case-by-case basis, taking into account the individual patient's risk factors and clinical presentation 4, 5.

Risks and Benefits

• The use of heparin in ischemic stroke patients is associated with a risk of bleeding complications, including cerebral hemorrhage and extracranial bleeding 4, 5, 3.
• However, anticoagulation with heparin may also be beneficial in preventing early neurological deterioration and improving the 6-month outcome in certain subpopulations of ischemic stroke patients 2, 6.