How to switch a patient with pulmonary embolism (PE) from Low Molecular Weight Heparin (LMWH) to a Direct Oral Anticoagulant (DOAC) after 5 days?

Switching from LMWH to DOAC After 5 Days of PE Treatment

For patients with pulmonary embolism who have been on LMWH for 5 days, switching to a DOAC should follow specific protocols based on the selected DOAC, with rivaroxaban or apixaban being preferred as they can be started immediately without overlap. 1

DOAC Selection and Transition Protocol

Option 1: Single-Drug Regimens (Preferred)

• Rivaroxaban:

  • Stop LMWH completely
  • Start rivaroxaban 15 mg twice daily for 21 days
  • Then continue with 20 mg once daily 1

• Apixaban:

  • Stop LMWH completely
  • Start apixaban 10 mg twice daily for 7 days
  • Then continue with 5 mg twice daily 1, 2

Option 2: LMWH-DOAC Combination Regimens

• Dabigatran:

  • After completing at least 5 days of LMWH (which you have)
  • Stop LMWH and start dabigatran 150 mg twice daily 1

• Edoxaban:

  • After completing at least 5 days of LMWH (which you have)
  • Stop LMWH and start edoxaban 60 mg once daily
  • Use 30 mg once daily if creatinine clearance 30-50 mL/min or body weight <60 kg 1

Timing of Transition

For all DOACs, administer the first dose of the DOAC at the time when the next LMWH dose would have been due:

• If LMWH was given twice daily: Give DOAC 12 hours after last LMWH dose
• If LMWH was given once daily: Give DOAC 24 hours after last LMWH dose 1

Clinical Considerations for DOAC Selection

1. Efficacy and Safety:

   • All DOACs are non-inferior to LMWH/VKA for preventing recurrent VTE 1
   • DOACs have lower risk of major bleeding compared to VKA (RR 0.63; 95% CI 0.47-0.84) 1

2. Patient-Specific Factors:

   • Renal function: Avoid DOACs with CrCl <30 mL/min; reduce edoxaban dose with CrCl 30-50 mL/min 1
   • Weight: Consider dose adjustment for edoxaban if <60 kg 1
   • Drug interactions: Check for medications affecting P-glycoprotein or CYP3A4 pathways

3. Practical Advantages:

   • Single-drug regimens (rivaroxaban, apixaban) simplify transition and reduce potential confusion 1
   • DOACs don't require routine monitoring like warfarin 1
   • DOACs are associated with shorter hospital stays compared to warfarin 1

Monitoring After Transition

1. Short-term follow-up (1-2 weeks after transition):

   • Assess for bleeding complications
   • Confirm medication adherence
   • Check renal function if baseline was borderline

2. Long-term follow-up (3-6 months):

   • Evaluate for signs of recurrent VTE
   • Assess for bleeding complications
   • Consider duration of anticoagulation based on risk factors 1

Common Pitfalls to Avoid

1. Inadequate duration of initial LMWH: Recent evidence suggests that <3 days of LMWH before switching to a DOAC is associated with worse outcomes compared to 3-5 days or >5 days of LMWH 3

2. Overlapping anticoagulation: For rivaroxaban and apixaban, LMWH should be discontinued completely before starting the DOAC to avoid excessive anticoagulation 1

3. Incorrect dosing: Using maintenance doses instead of loading doses during the initial treatment period (e.g., starting with 20 mg rivaroxaban instead of 15 mg twice daily) 2, 4

4. Failure to consider contraindications: DOACs should be avoided in patients with severe renal impairment, active cancer (in some cases), antiphospholipid syndrome, or high bleeding risk 1

By following these protocols, the transition from LMWH to DOAC after 5 days of PE treatment can be accomplished safely and effectively, maintaining anticoagulation while minimizing bleeding risk.