When to initiate early anticoagulation (anticoagulant therapy) in patients with stroke (cerebrovascular accident)?

From the Guidelines

Early anticoagulation in stroke should typically be initiated 3-14 days after an ischemic stroke, depending on stroke size and severity, as recommended by the most recent guidelines 1.

Key Considerations

• For small strokes, anticoagulation can begin around day 3, while larger strokes may require waiting 7-14 days to reduce hemorrhagic transformation risk.
• The specific timing should be individualized based on neuroimaging findings, stroke etiology (particularly for cardioembolic strokes like atrial fibrillation), and patient-specific bleeding risks.
• Common anticoagulants include direct oral anticoagulants (DOACs) such as apixaban, rivaroxaban, dabigatran, and edoxaban, or warfarin, with DOACs generally preferred for non-valvular atrial fibrillation due to lower intracranial bleeding risk 1.

Important Factors to Consider

• Bridging with heparin or low molecular weight heparin is typically not recommended in the acute phase, as it may increase the risk of symptomatic intracranial bleeding 1.
• The delay in anticoagulation allows time for the damaged blood-brain barrier to heal, reducing the risk of hemorrhagic transformation while balancing the need to prevent recurrent strokes.
• Patients with very large infarcts, hemorrhagic transformation on imaging, or uncontrolled hypertension may require longer delays before starting anticoagulation, as recommended by the 2021 guideline for the prevention of stroke in patients with stroke and transient ischemic attack 1.

Recommendations

• Initiate anticoagulation in patients with small strokes around day 3, and in patients with larger strokes after 7-14 days, depending on the individual risk of hemorrhagic transformation and recurrent stroke.
• Use neuroimaging findings and patient-specific factors to guide the timing of anticoagulation initiation.
• Prefer DOACs over warfarin for non-valvular atrial fibrillation due to their lower risk of intracranial bleeding 1.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Timing of Anticoagulation Initiation

The optimal timing of anticoagulation initiation in patients with stroke due to atrial fibrillation is a topic of ongoing debate. Several studies have investigated this issue, providing insights into the risks and benefits of early anticoagulation.

• A study published in 2023 2 reviewed the current evidence on the timing of anticoagulation after acute ischemic stroke in patients with atrial fibrillation, highlighting the need for larger randomized trials to determine the optimal timing of direct oral anticoagulant (DOAC) initiation.
• Another study from 2020 3 surveyed US stroke specialists and found that there is a lack of consensus regarding the timing of anticoagulation for secondary stroke prevention in patients with atrial fibrillation-related ischemic stroke.
• The AREST trial 4, published in 2021, compared early apixaban use with delayed warfarin initiation in patients with atrial fibrillation-related stroke or transient ischemic attack, and found that early apixaban use did not compromise patient safety.

Factors Influencing Anticoagulation Timing

Several factors can influence the timing of anticoagulation initiation, including:

• Stroke severity: A study from 2018 5 found that patients with hemorrhagic transformation (HT) initiated anticoagulant therapy later than those without HT.
• Presence of asymptomatic HT: The same study 5 found that patients with asymptomatic HT had a higher risk of mortality or disability at 90 days.
• Type of anticoagulant: A randomized clinical trial from 2017 6 compared rivaroxaban with warfarin in patients with mild atrial fibrillation-related ischemic stroke and found that both anticoagulants had comparable safety and efficacy.

Current Recommendations

Based on the available evidence, it appears that early anticoagulation may be safe and effective in patients with atrial fibrillation-related ischemic stroke, but the optimal timing of initiation remains unclear. Further studies are needed to determine the best approach for individual patients. The current recommendations are based on empiric expert opinion and may vary depending on the specific clinical scenario 2, 3.