What is the role of Direct Oral Anticoagulants (DOAC) in neurology?

From the Guidelines

Direct oral anticoagulants (DOACs) should be considered the preferred choice over vitamin K antagonists (VKAs) for stroke prevention in patients with non-valvular atrial fibrillation due to their superior safety profile and reduced risk of intracranial hemorrhage. The primary DOACs used in neurology include apixaban, rivaroxaban, dabigatran, and edoxaban, which have all demonstrated at least non-inferior efficacy compared with warfarin for the prevention of thromboembolism, but with the added benefit of a 50% reduction in intracranial haemorrhage (ICH) 1.

Key Benefits of DOACs

• Reduced risk of stroke or systemic embolism compared to warfarin, with a hazard ratio (HR) of 0.81 (95% CI, 0.73-0.91) 1
• Lower risk of all-cause mortality, with an HR of 0.90 (95% CI, 0.85-0.95) 1
• Significantly reduced risk of intracranial bleeding, with an HR of 0.48 (95% CI, 0.39-0.59) 1
• Predictable pharmacokinetics and fewer drug interactions compared to warfarin

Clinical Applications of DOACs

• Stroke prevention in non-valvular atrial fibrillation, with apixaban typically dosed at 5mg twice daily (reduced to 2.5mg twice daily in patients with at least two of: age ≥80, weight ≤60kg, or serum creatinine ≥1.5mg/dL)
• Secondary stroke prevention, generally started 3-14 days after an ischemic stroke, with timing dependent on stroke severity
• Cerebral venous thrombosis treatment, typically for 3-6 months or longer depending on risk factors

Important Considerations

• Caution is needed in patients with severe renal impairment
• Specific reversal agents (idarucizumab for dabigatran, andexanet alfa for factor Xa inhibitors) should be available for emergency situations
• Appropriate protocols for stopping and restarting these medications must be followed to minimize both bleeding and thrombotic risks, as supported by the 2021 guideline for the prevention of stroke in patients with stroke and transient ischemic attack 1 and the 2024 ESC guidelines for the management of atrial fibrillation 1

From the FDA Drug Label

The use of dabigatran etexilate capsules for the prophylaxis of thromboembolic events in patients with atrial fibrillation in the setting of other forms of valvular heart disease, including the presence of a bioprosthetic heart valve, has not been studied and is not recommended. Direct-acting oral anticoagulants (DOACs), including dabigatran etexilate capsules, are not recommended for use in patients with triple-positive antiphospholipid syndrome (APS) Direct-acting oral anticoagulants (DOACs), including XARELTO, are not recommended for use in patients with triple-positive antiphospholipid syndrome (APS)

The role of Direct Oral Anticoagulants (DOAC) in neurology is not explicitly stated in the provided drug labels. However, it can be inferred that DOACs, such as dabigatran 2 and rivaroxaban 3, are used to reduce the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation. Additionally, DOACs are not recommended for use in patients with triple-positive antiphospholipid syndrome (APS) due to increased rates of recurrent thrombotic events. Key points include:

• Contraindications: DOACs are contraindicated in patients with mechanical prosthetic valves and are not recommended for use in patients with triple-positive APS.
• Bleeding risk: DOACs carry a risk of bleeding, and patients should be monitored for signs and symptoms of blood loss.
• Renal impairment: DOACs should be used with caution in patients with renal impairment, as they may increase the risk of bleeding.

From the Research

Role of Direct Oral Anticoagulants (DOACs) in Neurology

The role of DOACs in neurology is primarily focused on the prevention of stroke and systemic embolism in patients with atrial fibrillation (AF).

• DOACs, including apixaban, dabigatran, edoxaban, and rivaroxaban, have been shown to be effective in reducing the risk of ischemic stroke and systemic embolism in patients with AF 4, 5.
• A study comparing the effectiveness and safety of apixaban, dabigatran, edoxaban, and rivaroxaban found that apixaban was associated with a lower risk of gastrointestinal bleeding (GIB) compared to the other DOACs 4.
• Another study found that apixaban may have a lower risk of major bleeding and comparable risk of stroke when compared with warfarin in AF patients with end-stage renal disease (ESRD) 6.

Safety and Efficacy of DOACs

The safety and efficacy of DOACs have been evaluated in several studies, including those in patients with chronic kidney disease (CKD) and ESRD.

• A review of the literature found that DOAC use in patients with CKD is increasing, despite the presence of a clear benefit, and with the potential for increased risk of bleeding compared to warfarin 7.
• A systematic review and meta-analysis found that apixaban may have a lower risk of major bleeding and comparable risk of stroke when compared with warfarin in AF patients with ESRD 6.
• A propensity score-matched cohort study found that high-dose apixaban was observed to have a better effectiveness and safety profile compared to high-dose rivaroxaban in patients with AF 8.

Clinical Considerations

Clinical considerations for the use of DOACs in neurology include the risk of bleeding, renal function, and the presence of other comorbidities.

• The risk of bleeding is a major concern with the use of DOACs, particularly in patients with CKD or ESRD 7, 6.
• Renal function is an important consideration when selecting a DOAC, as some DOACs may have altered pharmacokinetics in patients with renal failure 7.
• The presence of other comorbidities, such as hypertension or diabetes, may also impact the selection of a DOAC 5.