Is a loading dose of apixaban (apixaban) or rivaroxaban (rivaroxaban) needed when switching a patient with pulmonary embolism (PE) from Low Molecular Weight Heparin (LMWH) to apixaban or rivaroxaban after 7 days of LMWH therapy?

Switching from LMWH to Apixaban or Rivaroxaban After 7 Days: Loading Dose Not Required

When transitioning a PE patient from 7 days of LMWH to apixaban or rivaroxaban at discharge, you should start the standard loading dose regimen for each drug—this is not "additional" loading but rather the appropriate initial dosing for these agents, as they were designed to be started either with or without prior parenteral anticoagulation. 1, 2

Key Principle: DOACs Have Built-In Loading Regimens

The critical distinction here is that both apixaban and rivaroxaban have intrinsic loading dose regimens that were studied and approved regardless of prior anticoagulation status:

Rivaroxaban Dosing

• Start 15 mg orally twice daily for 21 days, then reduce to 20 mg once daily 1, 2
• This regimen was used in the EINSTEIN PE trial and does not require LMWH lead-in 1
• The 15 mg twice-daily dosing for 3 weeks IS the loading phase, providing higher drug exposure during the acute treatment period 1

Apixaban Dosing

• Start 10 mg orally twice daily for 7 days, then reduce to 5 mg twice daily 1, 3, 4, 2
• This regimen was used in the AMPLIFY study and does not require LMWH lead-in 1
• The 10 mg twice-daily dosing for 7 days IS the loading phase 3, 4, 2

Why Prior LMWH Doesn't Change the Dosing

The fact that your patient received 7 days of LMWH does not eliminate the need for the standard DOAC dosing regimen for several reasons:

• The landmark trials (EINSTEIN PE for rivaroxaban, AMPLIFY for apixaban) demonstrated safety and efficacy with these specific dosing regimens 1
• These regimens were designed as single-drug approaches that provide adequate anticoagulation throughout the treatment course 1
• The British Thoracic Society explicitly states that "rivaroxaban and apixaban can be used as part of a single-drug regimen without the need for an LMWH lead-in period" 1

Practical Transition Protocol

When switching from LMWH to apixaban or rivaroxaban:

1. Timing: Start the DOAC at the time of the next scheduled LMWH dose (do not overlap) 2

2. For Rivaroxaban:

   • Begin 15 mg twice daily for 21 days from the start date
   • Then continue 20 mg once daily 1

3. For Apixaban:

   • Begin 10 mg twice daily for 7 days from the start date
   • Then continue 5 mg twice daily 1, 3, 4, 2

4. No bridging required: The transition is direct without need for overlapping anticoagulation 1, 2

Common Pitfall to Avoid

Do not start directly at the maintenance dose (20 mg daily rivaroxaban or 5 mg twice-daily apixaban) thinking the patient has already been "loaded" with LMWH. The higher initial DOAC doses serve multiple purposes:

• Achieve rapid therapeutic levels of the specific DOAC 3, 4
• Provide the dosing regimen that was proven safe and effective in clinical trials 1
• Ensure adequate anticoagulation during the critical early treatment phase 3

Contrast with Dabigatran and Edoxaban

Unlike rivaroxaban and apixaban, dabigatran and edoxaban DO require at least 5 days of parenteral anticoagulation before initiation 1. In your scenario with 7 days of LMWH already given, these agents could be started at their standard maintenance doses without additional loading. However, the British Thoracic Society recommends using a single DOAC pathway to minimize confusion 1, and rivaroxaban/apixaban offer the advantage of single-drug regimens.

Renal Function Consideration

Ensure you check creatinine clearance before discharge, as this may affect DOAC dosing, particularly for rivaroxaban (15 mg once daily if CrCl 30-49 mL/min for maintenance phase) 1, 2