Are alternative anticoagulant medications, such as apixaban (Eliquis) and rivaroxaban (Xarelto), as effective as coumadin (warfarin) for patients with pulmonary embolism?

Alternative Anticoagulants for Pulmonary Embolism Treatment

When oral anticoagulation is initiated in a patient with pulmonary embolism who is eligible for a NOAC (apixaban, dabigatran, edoxaban, or rivaroxaban), a NOAC is the recommended form of anticoagulant treatment over warfarin (Coumadin). 1

Efficacy of NOACs vs. Warfarin

• NOACs (apixaban, dabigatran, edoxaban, and rivaroxaban) are non-inferior to standard therapy with warfarin for the treatment of pulmonary embolism in terms of preventing recurrent venous thromboembolism (VTE) and all-cause mortality. 1

• Rivaroxaban demonstrated non-inferiority to standard therapy (enoxaparin/warfarin) with 2.1% of patients experiencing recurrent VTE compared to 1.8% in the standard therapy group. 2

• Edoxaban was non-inferior to warfarin with respect to recurrent symptomatic VTE or fatal PE, with potentially better outcomes in patients with elevated NT-proBNP concentrations. 1

• Apixaban was non-inferior to conventional therapy (enoxaparin/warfarin) for prevention of recurrent VTE. 1

Safety Profile Advantages

• NOACs are associated with a lower risk of clinically relevant bleeding compared to warfarin therapy in patients treated for VTE. 1

• Major bleeding occurred less frequently with apixaban compared to conventional therapy (RR 0.31; 95% CI 0.17-0.55; P<0.001). 1

• Rivaroxaban showed lower rates of major bleeding (1.1%) compared to standard therapy (2.2%) (hazard ratio 0.49; 95% CI 0.31-0.79; P=0.003). 2

• The composite outcome of major bleeding and clinically relevant non-major bleeding occurred in 4.3% of patients in the apixaban group versus 9.7% in the conventional therapy group. 1

Practical Advantages of NOACs

• Rivaroxaban and apixaban can be used as part of a single-drug regimen without the need for an initial LMWH lead-in period, simplifying treatment. 1

• Treatment with NOACs may be associated with shorter length of hospital stay compared to warfarin therapy. 1

• NOACs do not require routine coagulation monitoring, unlike warfarin which requires regular INR testing. 3, 4

Special Considerations

• For patients with antiphospholipid antibody syndrome, indefinite treatment with a vitamin K antagonist (warfarin) is still recommended over NOACs. 1

• For extended anticoagulation beyond 6 months, a reduced dose of apixaban or rivaroxaban should be considered. 1

• NOACs are contraindicated during pregnancy and lactation. 1

• All NOACs have some degree of renal excretion and are contraindicated in severe renal failure (creatinine clearance <30 mL/min). 3

• For cancer patients with PE, edoxaban or rivaroxaban should be considered as alternatives to LMWH, except in patients with gastrointestinal cancer due to increased bleeding risk. 1

Clinical Algorithm for Anticoagulant Selection in PE

1. Assess patient eligibility for NOACs:

   • Check renal function (avoid in severe renal impairment) 3
   • Check liver function (anti-Xa inhibitors contraindicated in liver insufficiency) 3
   • Rule out antiphospholipid antibody syndrome (use warfarin) 1
   • Rule out pregnancy/lactation (use LMWH, not NOACs) 1

2. If eligible for NOACs, select one of the following based on patient characteristics:

   • Rivaroxaban: 15 mg twice daily for 3 weeks, followed by 20 mg once daily 2
   • Apixaban: 10 mg twice daily for 7 days, followed by 5 mg twice daily 1
   • Edoxaban: After ≥5 days of parenteral anticoagulation, 60 mg once daily (30 mg if CrCl 30-50 mL/min or weight <60 kg) 1
   • Dabigatran: After ≥5 days of parenteral anticoagulation, 150 mg twice daily 1

3. For extended treatment beyond 6 months, consider reduced doses:

   • Reduced dose of apixaban or rivaroxaban 1