When and how can Low Molecular Weight Heparin (LMWH) be switched to Direct Oral Anticoagulants (DOAC) in patients with Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE)?

Switching from LMWH to DOAC for DVT and PE

The timing and method of switching from LMWH to a DOAC depends entirely on which DOAC is selected: rivaroxaban and apixaban can be started immediately without any LMWH lead-in, while dabigatran and edoxaban require 5-10 days of LMWH before transitioning to the oral agent. 1

DOAC-Specific Switching Protocols

Immediate Transition (No LMWH Required)

Rivaroxaban:

• Start rivaroxaban 15 mg twice daily immediately upon diagnosis, without any LMWH pretreatment 1
• Continue 15 mg twice daily for the first 21 days 1
• Then reduce to 20 mg once daily for the remainder of treatment 1
• If LMWH has already been initiated, start rivaroxaban when the next LMWH dose would be due 2

Apixaban:

• Start apixaban 10 mg twice daily immediately upon diagnosis, without any LMWH pretreatment 1
• Continue 10 mg twice daily for the first 7 days 1
• Then reduce to 5 mg twice daily for the remainder of treatment 1
• If LMWH has already been initiated, start apixaban when the next LMWH dose would be due 2

Delayed Transition (LMWH Lead-In Required)

Dabigatran:

• Continue LMWH for a minimum of 5 days (up to 10 days acceptable) 1
• Start dabigatran 150 mg twice daily when the next LMWH dose would be due 1, 2
• Do not overlap dabigatran with LMWH 2
• The pharmacological rationale is that dabigatran has a delayed onset of action and requires the faster-acting LMWH to provide immediate anticoagulation while the oral agent reaches therapeutic levels 2

Edoxaban:

• Continue LMWH for a minimum of 5 days (up to 10 days acceptable) 1
• Start edoxaban 60 mg once daily when the next LMWH dose would be due 1
• Reduce to 30 mg once daily if creatinine clearance is 30-50 mL/min or body weight is <60 kg 1
• Do not overlap edoxaban with LMWH 1

Critical Timing Considerations

When LMWH Has Already Been Started:

• For rivaroxaban or apixaban: transition can occur at any time, even after just one dose of LMWH 1
• For dabigatran or edoxaban: must complete the full 5-10 day LMWH course before switching 1
• The transition should occur when the next LMWH dose would be due to avoid gaps in anticoagulation 2

Avoiding Common Pitfalls:

• Never overlap dabigatran or edoxaban with LMWH, as this increases bleeding risk without added benefit 2
• Never start dabigatran or edoxaban without the required LMWH lead-in, as this may result in inadequate initial anticoagulation 2
• Failure to properly time the transition can lead to increased risk of thrombotic events 2

Special Population Considerations

Renal Impairment:

• Apixaban may be preferred over dabigatran, as only a portion is renally eliminated 2
• Edoxaban requires dose reduction to 30 mg once daily if creatinine clearance is 30-50 mL/min 1
• All DOACs are contraindicated if creatinine clearance is <25-30 mL/min 1

Cancer-Associated Thrombosis:

• Apixaban has category 1 evidence supporting its use and does not require LMWH lead-in 2
• For patients with gastric or gastrointestinal malignancies, apixaban may be preferred over rivaroxaban or edoxaban due to lower GI bleeding rates 2

Antiphospholipid Syndrome:

• DOACs should be avoided; use adjusted-dose warfarin (target INR 2.5) instead 1

Drug Interactions:

• Patients requiring strong P-glycoprotein inhibitors/inducers or CYP3A4 inhibitors/inducers should use warfarin or LMWH rather than DOACs 1, 2

Treatment Duration After Switching

• All patients require a minimum 3-month treatment phase of anticoagulation regardless of which DOAC is selected 1
• Assess for extended-phase therapy at the conclusion of the 3-month treatment phase 1
• For provoked VTE with transient risk factors (e.g., surgery), stop anticoagulation after 3 months 1
• For unprovoked VTE or persistent risk factors, consider indefinite anticoagulation 1