What are the considerations for Eliquis (apixaban) after an embolic stroke?

From the Guidelines

Eliquis (apixaban) is a suitable option for patients after an embolic stroke, with a reduced risk of stroke or systemic embolism and lower risk of major bleeding compared to warfarin 1.

Key Considerations

• Dosing: The recommended dose of apixaban is 5 mg twice daily, with a reduced dose of 2.5 mg twice daily considered for patients with certain characteristics, such as age ≥80 years, weight ≤60 kg, or serum creatinine ≥1.5 mg/dL 1.
• Efficacy: Apixaban has been shown to be superior to warfarin in preventing stroke and systemic embolism, with a 21% reduction in stroke or systemic embolism and a 31% reduction in major bleeding 1.
• Safety: Apixaban has a lower risk of intracranial hemorrhage compared to warfarin, with a 51% reduction in hemorrhagic stroke 1.
• Renal Function: Apixaban may be considered in patients with a low creatinine clearance (15-30 mL/min), but its safety and efficacy have not been established in patients with more severe renal failure 1.

Patient Selection

• Nonvalvular Atrial Fibrillation: Apixaban is an efficacious alternative to aspirin in patients with nonvalvular AF deemed unsuitable for vitamin K antagonist therapy who have at least 1 additional risk factor and no more than 1 of the following characteristics: Age ≥80 years, weight ≤ 60 kg, or serum creatinine ≥1.5 mg/dL 1.
• Concomitant Antiplatelet Therapy: The safety and efficacy of combining apixaban with an antiplatelet agent have not been established 1. Some of the evidence provided may not be directly related to the question, such as the comparison of different DOACs or the use of apixaban in patients with valvular atrial fibrillation. However, the key considerations and patient selection criteria outlined above are based on the most relevant and high-quality evidence available 1.

From the FDA Drug Label

1 INDICATIONS & USAGE

1.1 Reduction of Risk of Stroke and Systemic Embolism in Nonvalvular Atrial Fibrillation Apixaban tablets are indicated to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation.

The considerations for Eliquis (apixaban) after an embolic stroke are to reduce the risk of recurrent stroke and systemic embolism in patients with nonvalvular atrial fibrillation.

• The drug is indicated for patients who have had an embolic stroke to prevent another stroke.
• Key points to consider are the patient's atrial fibrillation status and the risk of recurrent stroke. 2

From the Research

Considerations for Eliquis (Apixaban) after an Embolic Stroke

• The optimal timing to initiate anticoagulation after acute ischemic stroke (AIS) from atrial fibrillation (AF) is currently unknown 3
• Early anticoagulation may prevent recurrent infarctions but may provoke hemorrhagic transformation as AF strokes are typically larger and hemorrhagic transformation-prone 4
• The AREST trial compared early anticoagulation with apixaban in AF patients with stroke or transient ischemic attack (TIA) versus warfarin administration at later intervals, and found that apixaban had statistically similar yet generally numerically lower rates of recurrent strokes/TIA, death, fatal strokes, symptomatic hemorrhages, and the primary composite outcome of fatal stroke, recurrent ischemic stroke, or TIA 4
• The ARISTOTLE trial found that apixaban was superior to warfarin for stroke and systemic embolism prophylaxis, with lower rates of major bleeding 5, 6
• Apixaban has predictable pharmacodynamics and pharmacokinetics and does not require routine anticoagulation monitoring 5, 7
• The risk of intracranial hemorrhage was significantly lower with apixaban compared to warfarin 5, 7

Key Findings

• Early initiation of anticoagulation after TIA, small-, or medium-sized AIS from AF does not appear to compromise patient safety 4
• Apixaban is an important new option for use in patients with nonvalvular AF to reduce the risk of stroke or systemic embolism 5
• Further studies are needed to determine the long-term efficacy and safety of apixaban in patients with AF 5, 7

Study Designs and Rationale

• The AREST trial was an open-label, randomized controlled trial comparing the safety of early use of apixaban to warfarin in AF patients with stroke or TIA 4, 3
• The ARISTOTLE trial was a double-blind, double-dummy design comparing apixaban to warfarin in patients with AF and at least 1 additional risk factor for stroke 6
• The AVERROES trial compared apixaban to aspirin in patients with AF and at least 1 additional risk factor for stroke for whom vitamin K antagonist therapy was unsuitable 5