In an 80‑plus‑year‑old patient with advanced dementia, adequate renal function (creatinine clearance ≥ 30 mL/min), weight > 60 kg, and no bleeding risk, should I start apixaban (Eliquis) 10 mg twice daily for 7 days then 5 mg twice daily, or just 5 mg twice daily for three months?

Apixaban Dosing for Acute DVT in Advanced Dementia (Age ≥80)

Use the standard loading regimen of apixaban 10 mg twice daily for 7 days, then 5 mg twice daily thereafter. The patient's age ≥80 years alone does not trigger dose reduction; the FDA-approved algorithm requires at least two of the three dose-reduction criteria (age ≥80, weight ≤60 kg, serum creatinine ≥1.5 mg/dL), and the "2-of-3 rule" applies only to atrial fibrillation, not to acute VTE treatment. 1, 2

Why the Standard VTE Dose Is Correct

• The dose-reduction criteria used for atrial fibrillation do not apply to acute DVT or PE treatment. The FDA label explicitly states that for VTE treatment, the initial dose is 10 mg twice daily for 7 days, followed by 5 mg twice daily, with no renal or age-based adjustments unless creatinine clearance falls below 15 mL/min. 1, 2

• Age ≥80 years is only one criterion; you need ≥2 criteria to reduce the dose in atrial fibrillation, and even then, this rule does not extend to VTE. The patient would need to meet at least two of the following—age ≥80, weight ≤60 kg, or serum creatinine ≥1.5 mg/dL—to justify 2.5 mg twice daily in the atrial fibrillation indication, but this algorithm is irrelevant for acute thrombosis. 2, 1

• Apixaban has only 27% renal clearance, making it safe across a wide range of renal function and age groups. This low renal dependence provides a safety margin even in elderly patients with fluctuating kidney function. 2

Evidence Supporting Standard VTE Dosing

• The pivotal VTE trials (AMPLIFY) used 10 mg twice daily for 7 days, then 5 mg twice daily, without age-based dose reduction. This regimen was studied and approved for all patients with acute DVT or PE, including those ≥80 years old. 2, 1

• In patients with dementia and atrial fibrillation, apixaban demonstrated lower rates of major bleeding and ischemic stroke compared with warfarin, dabigatran, and rivaroxaban. The absolute risk reduction was even greater in patients with dementia (29.8 events per 1000 person-years for warfarin vs. apixaban, compared with 16.0 events per 1000 person-years in those without dementia), supporting apixaban's safety in this vulnerable population. 3

• Patients with isolated advanced age (≥80 years) who received apixaban 5 mg twice daily in the ARISTOTLE trial had similar efficacy and safety compared with those without dose-reduction criteria. The hazard ratio for major bleeding was 0.68 (95% CI 0.53–0.87) for apixaban vs. warfarin in patients with one dose-reduction criterion, confirming that age alone does not mandate dose reduction. 4

Practical Implementation

1. Start apixaban 10 mg orally twice daily immediately (no bridging with heparin is required). 1, 2

2. Continue 10 mg twice daily for exactly 7 days, then switch to 5 mg twice daily. 1, 2

3. Treat for a minimum of 3 months, then reassess for extended therapy based on provoking factors (unprovoked DVT warrants indefinite anticoagulation; provoked DVT may allow discontinuation after 3–6 months). 1, 2

4. After 6 months of treatment, consider reducing to 2.5 mg twice daily for extended secondary prevention if the patient has completed initial therapy and you are transitioning to long-term prophylaxis. 1, 2

Renal Function Considerations

• Calculate creatinine clearance using the Cockcroft-Gault equation (not eGFR), as this method was used in the pivotal trials and FDA labeling. 2, 1

• If CrCl ≥30 mL/min, use the standard VTE dose (10 mg BID × 7 days, then 5 mg BID). No adjustment is needed unless CrCl falls below 15 mL/min. 2, 1

• If CrCl 15–29 mL/min, use 2.5 mg twice daily for atrial fibrillation, but for acute VTE, the FDA label does not mandate dose reduction. Clinical judgment is required; some experts use 5 mg twice daily with close monitoring. 2, 1

• Reassess renal function at least annually, or every 3–6 months if CrCl <60 mL/min. 2

Dementia-Specific Considerations

• Apixaban is the preferred anticoagulant in patients with dementia and atrial fibrillation, with lower rates of major bleeding and stroke compared with warfarin, dabigatran, and rivaroxaban. The adjusted rate difference for major bleeding was 29.8 events per 1000 person-years greater with warfarin vs. apixaban in patients with dementia, compared with 16.0 events per 1000 person-years in those without dementia. 3

• Ensure the patient or caregiver can reliably administer twice-daily dosing. If adherence is a concern, consider once-daily rivaroxaban (15 mg daily for DVT treatment if CrCl 30–50 mL/min, or 20 mg daily if CrCl >50 mL/min), though apixaban has superior bleeding safety. 5, 3

• Assess fall risk, but do not withhold anticoagulation solely based on fall risk. The absolute stroke risk from untreated DVT exceeds the intracranial bleeding risk from falls, and apixaban reduces intracranial hemorrhage by 49% compared with warfarin. 2

Common Pitfalls

• Do not reduce the dose to 2.5 mg twice daily based on age alone. The "2-of-3 rule" applies only to atrial fibrillation, and even then, requires at least two criteria. 2, 1

• Do not use eGFR for dosing decisions; always calculate CrCl with Cockcroft-Gault. Reliance on eGFR can lead to dosing errors. 2

• Do not add aspirin or other antiplatelet agents unless there is an absolute indication (e.g., recent ACS), as this substantially increases bleeding risk. 2

• Do not bridge with heparin when starting apixaban for acute DVT. The 10 mg twice-daily loading dose provides immediate therapeutic anticoagulation. 1, 2

Monitoring

• No routine INR monitoring is required. 2, 1

• Monitor for signs of bleeding (especially gastrointestinal) and thrombosis (chest pain, dyspnea, leg swelling). 2

• Check CBC and renal function at baseline and periodically during treatment. 2