From the Guidelines
The ADVOCATE trial is not directly mentioned in the provided evidence, however, based on the available information from the ARISTOTLE trial, apixaban was superior to warfarin for the prevention of stroke or systemic embolization among patients with atrial fibrillation or atrial flutter and at least 1 additional risk factor for stroke. The study found that apixaban demonstrated a lower rate of major bleeding compared to warfarin, with a significant reduction in hemorrhagic stroke 1. The standard dosing of apixaban in this population was 5 mg twice daily, with a reduced dose of 2.5 mg twice daily for patients meeting at least two of the following criteria: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL 1. Some key points to consider when using apixaban include:
- Apixaban does not require routine INR monitoring, making it more convenient for patients
- Apixaban has a more predictable anticoagulant effect and fewer food and drug interactions compared to warfarin
- However, it's essential to note that apixaban is contraindicated in patients with severe renal impairment (creatinine clearance <15 mL/min) and requires dose adjustment for moderate renal impairment
- The trial results support the use of apixaban as an effective alternative to warfarin for stroke prevention in atrial fibrillation patients, particularly for those who have difficulty maintaining a therapeutic INR range or experience bleeding complications on warfarin therapy 1. Key benefits of apixaban include:
- Reduced risk of hemorrhagic stroke
- Lower rate of major bleeding compared to warfarin
- Convenient dosing without the need for routine INR monitoring
- More predictable anticoagulant effect and fewer food and drug interactions compared to warfarin.
From the FDA Drug Label
The FDA drug label does not answer the question.
From the Research
Overview of the ADVOCATE Trial
- The ADVOCATE trial is not directly mentioned in the provided evidence, however, the Apixaban Versus Vitamin K Antagonist (AVK) trials are discussed in the context of apixaban for stroke prevention in atrial fibrillation 2, 3, 4, 5, 6.
- The ARISTOTLE trial compared apixaban with warfarin in 18,201 patients with atrial fibrillation and ≥ 1 additional risk factor for stroke, demonstrating the superiority of apixaban over warfarin for the primary outcome of preventing stroke or systemic embolism 2.
Key Findings
- Apixaban reduced the risk of stroke or systemic embolism by 21% compared with warfarin (1.27% vs 1.60% per year; hazard ratio, 0.79; 95% confidence interval, 0.66-0.95) 2.
- Apixaban also reduced all-cause mortality by 11% (P = 0.047) and major bleeding by 31% (P < 0.001) compared with warfarin 2.
- A meta-analysis comparing the efficacy and safety of apixaban and warfarin in preventing stroke among patients with non-valvular atrial fibrillation found that apixaban was associated with a significant decrease in stroke or systemic embolism (RR: 0.77,95% CI: 0.67-0.90) and major bleeding events (RR=0.63,95% CI: 0.58-0.68) compared with warfarin 3.
Real-World Use and Subclinical Atrial Fibrillation
- Real-world studies on the use of apixaban for stroke prevention in atrial fibrillation have shown that apixaban is associated with a similar effectiveness in reducing stroke and any thromboembolic events when compared with warfarin, and a better safety profile 4.
- A trial involving patients with subclinical atrial fibrillation found that apixaban resulted in a lower risk of stroke or systemic embolism than aspirin but a higher risk of major bleeding 6.