What is the role of Eliquis (apixaban) in the treatment of pulmonary embolism?

Apixaban (Eliquis) in the Treatment of Pulmonary Embolism

Apixaban is a first-line treatment option for pulmonary embolism (PE), with a recommended dosing of 10 mg twice daily for 7 days followed by 5 mg twice daily, demonstrating non-inferiority to conventional therapy with significantly lower bleeding risk. 1, 2

FDA-Approved Indications

• Apixaban is specifically FDA-approved for the treatment of pulmonary embolism 2
• Also approved for reducing the risk of recurrent DVT and PE following initial therapy 2

Dosing Regimen

• Initial treatment: 10 mg twice daily for the first 7 days 1, 2
• Maintenance therapy: 5 mg twice daily for at least 3 months 1, 2
• Extended prevention of recurrence: 2.5 mg twice daily after completing at least 6 months of treatment 2

Efficacy

• Apixaban is non-inferior to conventional therapy (enoxaparin/warfarin) for preventing recurrent VTE or VTE-related death 1, 3
• In the AMPLIFY trial (n=5395), the primary efficacy outcome of recurrent VTE occurred in 2.3% of apixaban patients versus 2.7% in the conventional therapy group (relative risk 0.84; 95% CI 0.60-1.18) 3
• Real-world data shows 25-39% lower risk of recurrent VTE compared to warfarin across different subgroups and time points 4

Safety Profile

• Significantly lower major bleeding rates compared to conventional therapy: 0.6% vs 1.8% (relative risk 0.31; 95% CI 0.17-0.55; p<0.001) 1, 3
• Composite outcome of major bleeding plus clinically relevant non-major bleeding was also significantly reduced with apixaban: 4.3% vs 9.7% (relative risk 0.44; 95% CI 0.36-0.55; p<0.001) 1, 3
• Consistent safety advantage observed across different patient subgroups 4

Advantages Over Conventional Therapy

• Fixed dosing without need for routine anticoagulation monitoring 5
• No requirement for initial parenteral anticoagulation (unlike dabigatran and edoxaban) 1
• Predictable pharmacological properties 5
• Reduced risk of major bleeding compared to warfarin 1, 3

Special Populations

Cancer-Associated PE

• Apixaban is non-inferior to dalteparin for cancer-associated VTE without increased bleeding risk 6
• The Caravaggio trial showed recurrent VTE in 5.6% of apixaban patients vs 7.9% with dalteparin (HR 0.63; 95% CI 0.37-1.07) 6
• Major bleeding rates were similar: 3.8% with apixaban vs 4.0% with dalteparin 6
• For cancer patients, the CHEST guidelines suggest using direct oral anticoagulants like apixaban over low molecular weight heparin 1, 7

Renal Impairment

• Apixaban should be avoided in patients with severe renal impairment (CrCl <15 mL/min) 7
• Regular monitoring of renal function is recommended during treatment 7

Important Considerations and Potential Pitfalls

Temporary Interruption for Procedures

• Discontinue apixaban at least 48 hours prior to elective surgery with moderate/high bleeding risk 2
• Discontinue at least 24 hours prior to procedures with low bleeding risk 2
• Resume after adequate hemostasis is established 2

Risk of Premature Discontinuation

• Premature discontinuation increases thrombotic risk 2
• If discontinuing for reasons other than bleeding or completion of therapy, consider bridging with another anticoagulant 2

Monitoring Requirements

• While routine coagulation monitoring is not required, regular assessment for signs of recurrent VTE or bleeding complications is recommended 7
• Annual reassessment of the risk-benefit balance for extended therapy 7

Duration of Therapy

• Minimum 3 months of treatment for most patients with PE 1
• Extended anticoagulation should be considered for unprovoked PE or those with persistent risk factors 1, 7
• For extended treatment beyond initial therapy, consider reduced dose (2.5 mg twice daily) 7

In conclusion, apixaban represents an effective, convenient, and safer alternative to conventional anticoagulation therapy for patients with pulmonary embolism, with particular advantages in reducing bleeding complications while maintaining efficacy in preventing recurrent VTE.