What is the risk of death associated with long-term use of apixaban (eliquis) 10mg?

Risk of Death Associated with Long-term Apixaban 10mg Use

Long-term use of apixaban 10mg daily (given as 5mg twice daily) carries an increased risk of bleeding complications without providing additional efficacy benefits compared to standard dosing, and therefore is not recommended for extended anticoagulation therapy. 1

Apixaban Dosing and Safety Profile

Apixaban is an oral direct factor Xa inhibitor primarily metabolized via the liver with approximately 27% renal elimination. Its standard dosing varies by indication:

• For venous thromboembolism (VTE) treatment: 10mg twice daily for 7 days followed by 5mg twice daily 1
• For extended VTE prevention: 2.5mg twice daily 2
• For atrial fibrillation: 5mg twice daily with dose reduction to 2.5mg twice daily in specific populations 1

Mortality Risk Evidence

The AMPLIFY trial demonstrated that apixaban at standard dosing (10mg twice daily for 7 days followed by 5mg twice daily for 6 months) was associated with:

• No increased all-cause mortality compared to conventional therapy
• Significantly lower major bleeding risk (0.6% vs 1.8%, relative risk 0.31) 1

For extended treatment beyond the initial period, the AMPLIFY-EXT trial showed:

• Death from any cause was 1.7% in placebo group vs 0.8% in 2.5mg apixaban group and 0.5% in 5mg apixaban group 2
• No additional efficacy benefit was observed with 5mg twice daily compared to 2.5mg twice daily

Bleeding Risk with High-Dose Apixaban

The risk of major bleeding with apixaban increases with higher dosing:

• In the AMPLIFY trial, major bleeding with standard therapeutic dosing was 0.6% 1
• For extended treatment, major bleeding rates were 0.2% with 2.5mg twice daily and 0.1% with 5mg twice daily 2
• Clinically relevant non-major bleeding was higher with 5mg twice daily (4.2%) compared to 2.5mg twice daily (3.0%) 2

Special Populations and Contraindications

Apixaban should be avoided in:

• Severe renal impairment (CrCl <15 mL/min) 1
• Hepatic impairment (transaminases >2 times upper limit of normal or total bilirubin >1.5 times upper limit of normal) 1
• Mechanical heart valves (contraindicated based on evidence from dabigatran studies) 1

Dose Reduction Criteria

Dose reduction to 2.5mg twice daily is indicated if at least 2 of the following are present:

• Age ≥80 years
• Body weight ≤60 kg
• Serum creatinine ≥1.5 mg/dL (133 μmol/L) 1

Long-term Use Considerations

For extended anticoagulation therapy beyond the initial treatment period:

• The 2.5mg twice daily dose is preferred for secondary prevention of VTE 2
• No evidence supports using 10mg daily long-term
• Recent studies show that low-dose apixaban (2.5mg twice daily) is effective and safe for secondary VTE prophylaxis with a median follow-up of over 2 years 3

Clinical Algorithm for Long-term Anticoagulation

1. Complete initial treatment phase with standard dosing
2. For extended therapy beyond 6 months:
   • Use reduced dose of 2.5mg twice daily for most patients
   • Consider continuing 5mg twice daily only in patients with:
     • Active cancer
     • Multiple recurrent VTE episodes
     • High thrombotic risk with low bleeding risk
3. Avoid 10mg daily dosing for long-term therapy
4. Monitor for bleeding complications regularly
5. Reassess need for continued anticoagulation periodically

Key Pitfalls to Avoid

1. Using high-dose apixaban (10mg daily) for extended therapy increases bleeding risk without improving efficacy
2. Failing to adjust dose based on age, weight, and renal function
3. Not recognizing contraindications such as severe renal impairment or mechanical heart valves
4. Overlooking drug interactions that may increase apixaban levels

In conclusion, while apixaban is effective for anticoagulation, the 10mg daily dose should be limited to the initial 7-day treatment period for VTE, with lower doses used for long-term therapy to minimize mortality and bleeding risks.