What is the dosing regimen for transitioning from injectable heparin to oral anticoagulants, such as Apixaban (apixaban) or Rivaroxaban (rivaroxaban), for patients with pulmonary embolism?

Transitioning from Injectable Heparin to Oral Anticoagulation for Pulmonary Embolism

For pulmonary embolism, you can transition directly from heparin to oral anticoagulants using either a single-drug approach with rivaroxaban or apixaban (no overlap needed), or switch to dabigatran or edoxaban after at least 5 days of parenteral anticoagulation. 1

Direct Transition Options (No Heparin Overlap Required)

Rivaroxaban - Single Drug Approach

• Start rivaroxaban 15 mg twice daily for 3 weeks, then reduce to 20 mg once daily 1, 2
• Discontinue heparin and begin rivaroxaban at the time of the next scheduled heparin dose 3
• This regimen demonstrated non-inferior efficacy with significantly lower major bleeding (1.1% vs 2.2%) compared to standard therapy 1, 2

Apixaban - Single Drug Approach

• Start apixaban 10 mg twice daily for 7 days, then reduce to 5 mg twice daily 1, 3
• Discontinue heparin and begin apixaban at the time of the next scheduled heparin dose 3
• This showed superior safety with major bleeding of only 0.6% versus 1.8% with conventional therapy 1

Transition After Minimum Heparin Course

Dabigatran

• Continue heparin for at least 5 days (mean 10 days in trials) 1
• Then start dabigatran 150 mg twice daily 1
• Discontinue heparin when starting dabigatran 1

Edoxaban

• Continue heparin for at least 5 days 1
• Then start edoxaban 60 mg once daily 1
• Reduce to 30 mg once daily if: 1
  • Creatinine clearance 30-50 mL/min, OR
  • Body weight <60 kg

Critical Renal Function Considerations

Severe renal impairment (CrCl <30 mL/min): 1

• Continue unfractionated heparin - do NOT use NOACs 1
• NOACs are contraindicated in this population 1, 3

Moderate renal impairment (CrCl 30-60 mL/min): 1

• Rivaroxaban, apixaban, and dabigatran: use standard doses 1
• Edoxaban: reduce to 30 mg once daily 1

Mild renal impairment (CrCl 15-30 mL/min with LMWH): 1

• Use adapted LMWH dosing scheme if continuing parenteral therapy 1

Extended Anticoagulation After Initial Treatment

After completing 6 months of therapeutic anticoagulation, consider reduced-dose maintenance: 1, 4

• Apixaban 2.5 mg twice daily (Class IIa, Level A) 1, 4
• Rivaroxaban 10 mg once daily (Class IIa, Level A) 1
• Dabigatran and edoxaban: maintain full therapeutic doses if continuing (reduced-dose regimens not studied for extension) 1

Important Contraindications and Special Populations

Antiphospholipid antibody syndrome: 1, 4

• Do NOT use NOACs 1, 4
• Use vitamin K antagonist (warfarin) indefinitely 1

Cancer-associated PE: 1, 4

• Prefer LMWH, edoxaban, or rivaroxaban over apixaban 4
• Continue indefinitely or until cancer is cured 1

Pregnancy and lactation: 4

• Apixaban and all NOACs are contraindicated 4

Common Pitfalls to Avoid

• Do not overlap heparin with rivaroxaban or apixaban - these use higher initial doses that provide immediate therapeutic anticoagulation 1, 3
• Do not start dabigatran or edoxaban too early - minimum 5 days of parenteral anticoagulation is required 1
• Do not use standard NOAC doses in severe renal impairment - this significantly increases bleeding risk 1, 3
• Do not forget the higher initial loading doses - rivaroxaban 15 mg BID (not 20 mg) for 3 weeks and apixaban 10 mg BID (not 5 mg) for 7 days are essential 1, 3