Eliquis (Apixaban) Guidelines for Anticoagulation
Standard Dosing for Atrial Fibrillation
For stroke prevention in nonvalvular atrial fibrillation, apixaban 5 mg twice daily is the standard dose for most patients, with dose reduction to 2.5 mg twice daily only when patients meet at least TWO of the following criteria: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL. 1
Key Dosing Principles
Direct Oral Anticoagulants (DOACs), including apixaban, are recommended over warfarin for eligible patients with nonvalvular AF (excluding moderate-to-severe mitral stenosis or mechanical heart valves). 2
The European Society of Cardiology (2024) identifies apixaban as a preferred anticoagulant, demonstrating superior outcomes compared to warfarin with 21% reduction in stroke/systemic embolism, 31% reduction in major bleeding, and 11% reduction in all-cause mortality. 2
Apixaban is the only NOAC that has been directly compared to aspirin, showing 55% reduction in stroke or systemic embolism compared to aspirin without increased major bleeding. 2
Indications for Anticoagulation
Risk Stratification
Oral anticoagulation is strongly recommended for patients with CHA₂DS₂-VASc score ≥2 in men or ≥3 in women. 2
For CHA₂DS₂-VASc score = 1 in men or 2 in women, anticoagulation should be considered. 2
The CHA₂DS₂-VASc scoring system assigns points as follows: Congestive heart failure (+1), Hypertension (+1), Age ≥75 years (+2), Diabetes (+1), Prior stroke/TIA/thromboembolism (+2), Vascular disease (+1), Age 65-74 years (+1), Female sex (+1). 2
Important Exclusions
Apixaban is contraindicated in patients with moderate-to-severe mitral stenosis or mechanical heart valves—these patients require warfarin. 2
Patients with bioprosthetic valves, valve repair, or mild valvular disease can receive apixaban. 2
Dose Reduction Criteria: Critical Clinical Caveat
The presence of only ONE dose-reduction criterion (age ≥80, weight ≤60 kg, OR creatinine ≥1.5 mg/dL) does NOT warrant dose reduction—patients require at least TWO criteria to justify the 2.5 mg twice daily dose. 1, 3
Evidence Supporting Standard Dosing with Single Criteria
In the ARISTOTLE trial, patients with only one dose-reduction criterion who received 5 mg twice daily showed consistent benefits compared to warfarin for both stroke prevention (HR 0.94 for one criterion vs HR 0.77 for no criteria, p for interaction = 0.36) and major bleeding reduction (HR 0.68 vs HR 0.72, p for interaction = 0.71). 3
Patients with isolated advanced age, low body weight, or renal dysfunction have higher baseline risk but demonstrate consistent safety and efficacy with the standard 5 mg twice daily dose. 3
Common Prescribing Error
Real-world data shows that 60.8% of patients receiving reduced-dose apixaban do not meet labeling criteria for dose reduction, with age, weight, and creatinine being independent predictors of inappropriate underdosing. 4
This inappropriate dose reduction may expose patients to inadequate anticoagulation and increased stroke risk. 4
Drug Interactions Requiring Dose Adjustment
When apixaban 5 mg or 10 mg twice daily is coadministered with combined P-glycoprotein AND strong CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir), reduce the dose by 50%. 1
- For patients already taking 2.5 mg twice daily, avoid coadministration with these combined inhibitors entirely. 1
Renal Function Considerations
Renal function assessment is essential before initiating apixaban and should be reassessed at least annually, as declining renal function increases drug accumulation and bleeding risk. 2, 5
Renal Dosing Specifics
Apixaban has 27% renal excretion with a half-life of 9-14 hours. 2
The drug should be avoided in patients with creatinine clearance <15 mL/min (patients with CrCl <25 mL/min were excluded from clinical trials). 2
Post-hoc analyses demonstrate consistent efficacy in patients with impaired renal function (eGFR <80 mL/min) and significantly greater reduction in major bleeding among those with eGFR ≤50 mL/min. 2
Other Indications and Dosing
VTE Treatment
For acute DVT/PE treatment: 10 mg twice daily for 7 days, then 5 mg twice daily. 1
For reduction in recurrence risk after completing ≥6 months of treatment: 2.5 mg twice daily. 1
VTE Prophylaxis Post-Surgery
- Hip or knee replacement: 2.5 mg twice daily starting 12-24 hours post-surgery (35 days for hip, 12 days for knee). 1
Perioperative Management
Discontinue apixaban at least 48 hours before elective surgery with moderate-to-high bleeding risk, or at least 24 hours before procedures with low bleeding risk. 1
Bridging anticoagulation during the 24-48 hour interruption is not generally required. 1
Resume apixaban as soon as adequate hemostasis is established after the procedure. 1
Switching Between Anticoagulants
From Warfarin to Apixaban
- Discontinue warfarin and start apixaban when INR <2.0. 1
From Apixaban to Warfarin
Discontinue apixaban and begin both parenteral anticoagulant and warfarin at the time of the next apixaban dose; discontinue parenteral anticoagulant when INR reaches therapeutic range. 1
Note that apixaban affects INR measurements during transition, making initial INR values unreliable for warfarin dosing. 1
From/To Other Anticoagulants
- Simply discontinue one agent and begin the other at the time of the next scheduled dose. 1
Management of Bleeding Complications
For hemodynamically stable patients with gastrointestinal bleeding on apixaban, hold the medication and consult gastroenterology—reversal agents are reserved exclusively for life-threatening, uncontrolled bleeding. 6
Reversal Agent Considerations
Andexanet alfa achieved 93% reduction in anti-Xa activity and 80% hemostatic efficacy at 12 hours, but was studied only in patients with hemodynamic compromise. 6
Thromboembolic events occurred in 10.3% of patients receiving andexanet versus 5.6% with usual care (absolute increase of 4.6 per 100 patients). 6
Resumption After Bleeding
Resume apixaban as soon as adequate hemostasis is established, without waiting for a specific time interval, as thromboembolic risk in AF patients is substantial. 6
Timing depends on adequacy of hemostasis, severity of bleeding episode, and stroke risk (CHA₂DS₂-VASc score). 6
Administration Options
For patients unable to swallow whole tablets, apixaban may be crushed and suspended in water, D5W, or apple juice, or mixed with applesauce and administered immediately. 1
Crushed tablets may also be suspended in 60 mL of water or D5W and delivered via nasogastric tube. 1
Crushed apixaban remains stable in these vehicles for up to 4 hours. 1
Critical Safety Warnings
A black box warning exists for apixaban discontinuation—coverage with another anticoagulant should be strongly considered at cessation unless pathological bleeding is present, due to clustering of stroke events after discontinuation. 2
Antiplatelet therapy alone (including aspirin) should NOT be used for stroke prevention in AF patients eligible for oral anticoagulation, as aspirin offers only 19% stroke reduction with minimal benefit for disabling cardioembolic strokes. 7
Avoid combining anticoagulants with antiplatelet agents unless the patient has an acute vascular event or needs interim treatment for procedures. 2