Reviewed by MedNext Clinical Team
Apixaban is a direct oral factor Xa inhibitor and has become one of the most widely prescribed anticoagulants globally. Its predictable pharmacokinetics, lack of routine monitoring requirement, and favourable benefit-risk profile in pivotal trials have made it the preferred DOAC in many clinical settings [1]. However, dose selection, renal function assessment, and perioperative management require careful attention.
Mechanism of Action
Apixaban directly and reversibly inhibits factor Xa — the enzyme at the convergence of the intrinsic and extrinsic coagulation cascades — preventing the conversion of prothrombin to thrombin. Unlike warfarin, it does not require monitoring of coagulation parameters under routine conditions. Its half-life of 8–15 hours allows twice-daily dosing.
Atrial Fibrillation: Stroke Prevention
For non-valvular AF, the standard dose is 5 mg twice daily. The ARISTOTLE trial demonstrated that apixaban was superior to warfarin in reducing stroke or systemic embolism, with significantly lower rates of major bleeding and all-cause mortality [1]. Apixaban should be used in patients with a CHA₂DS₂-VASc score of 2 or more in men, and 3 or more in women.
VTE Treatment and Prevention
For acute DVT or PE treatment, apixaban is given at 10 mg twice daily for 7 days (treatment phase), followed by 5 mg twice daily for at least 3 months (maintenance phase). For extended secondary prevention after completion of initial treatment, the dose can be reduced to 2.5 mg twice daily. For VTE prophylaxis following hip or knee replacement surgery, 2.5 mg twice daily is used.
Dose Reduction Criteria in AF
The standard 5 mg twice daily dose should be reduced to 2.5 mg twice daily in AF patients who meet at least two of the following three criteria:
- Age 80 years or older
- Body weight 60 kg or less
- Serum creatinine 133 micromol/L or higher
Applying only one of these criteria does not warrant dose reduction. Incorrect dose reduction in patients who do not meet criteria is a common prescribing error that may result in inadequate stroke prevention.
Renal Function Thresholds
Approximately 27% of apixaban is eliminated renally. In severe renal impairment (creatinine clearance 15–29 mL/min), the dose in AF should be reduced to 2.5 mg twice daily regardless of other criteria. Apixaban is not recommended in patients on dialysis for AF (limited evidence) and is contraindicated in severe hepatic impairment. Regular reassessment of renal function — at least annually in stable patients, and more frequently in those with progressive kidney disease or acute illness — is important.
Perioperative Management
For elective procedures with standard bleeding risk, apixaban should be withheld for at least 24 hours before the procedure (48 hours for high bleeding risk procedures or if renal function is impaired). There is generally no need for bridging with heparin in AF patients — the risks of bridging typically outweigh the benefits. Restart apixaban as soon as haemostasis is achieved, typically 24–48 hours post-procedure.
Reversal
Andexanet alfa is a specific reversal agent for apixaban (and rivaroxaban) approved for life-threatening or uncontrolled bleeding. Where andexanet is unavailable, four-factor prothrombin complex concentrate (PCC) can be used as an alternative. Unlike warfarin, routine reversal with vitamin K is not applicable to apixaban.
References
- Granger CB, Alexander JH, McMurray JJV, et al. Apixaban versus warfarin in patients with atrial fibrillation. NEJM. 2011;365:981-992.