What oral anticoagulants are used for DVT and PE?

Oral Anticoagulants for DVT and PE Treatment

Direct oral anticoagulants (DOACs) including rivaroxaban, apixaban, dabigatran, and edoxaban are the preferred oral anticoagulants for DVT and PE treatment due to their favorable efficacy, safety profile, and convenience compared to vitamin K antagonists. 1

First-Line Oral Anticoagulant Options

Direct Oral Anticoagulants (DOACs)

1. Rivaroxaban

   • Dosing: 15 mg twice daily for 21 days, then 20 mg once daily 1
   • Advantages: Single-drug approach (no need for initial parenteral anticoagulation) 1
   • Evidence: EINSTEIN trials showed non-inferiority to standard therapy with significantly lower major bleeding rates 2

2. Apixaban

   • Dosing: 10 mg twice daily for 7 days, then 5 mg twice daily 1
   • Advantages: Single-drug approach with lower bleeding risk 1

3. Dabigatran

   • Dosing: 150 mg twice daily after 5-10 days of parenteral anticoagulation 3
   • Note: Requires initial parenteral anticoagulation 1

4. Edoxaban

   • Dosing: 60 mg once daily (30 mg once daily if CrCl 15-50 mL/min, weight ≤60 kg, or on P-gp inhibitors) after 5-10 days of parenteral anticoagulation 1
   • Note: Requires initial parenteral anticoagulation 1

Vitamin K Antagonists (Second-line)

• Warfarin (target INR 2.0-3.0) with initial parenteral anticoagulation overlap 4
• Less preferred due to need for monitoring, drug-food interactions, and slower onset/offset of action 1

Selection Factors for Specific DOACs

Patient-Specific Considerations

1. Renal Function:

   • CrCl <30 mL/min: Avoid rivaroxaban, apixaban, edoxaban; dabigatran dose reduction to 75 mg BID if CrCl 15-30 mL/min 1, 3
   • CrCl 30-50 mL/min: Consider dose adjustments for edoxaban and rivaroxaban 1

2. Cancer Patients:

   • DOACs are acceptable alternatives to LMWH for cancer-associated thrombosis 1
   • Apixaban and rivaroxaban have been specifically studied in cancer populations 1

3. Outpatient vs. Inpatient:

   • For outpatient COVID-19 patients with DVT/PE: DOACs are recommended first-line 1
   • For hospitalized patients: Consider parenteral anticoagulation initially 1

4. Drug Interactions:

   • Avoid DOACs with strong P-gp inducers 3
   • Reduce dose or avoid DOACs with P-gp inhibitors in patients with CrCl 30-50 mL/min 3
   • Consider drug interactions with CYP3A4 inhibitors/inducers for rivaroxaban and apixaban 1

Treatment Duration

1. Minimum duration: 3 months for all patients with DVT/PE 1

2. Extended duration considerations:

   • First episode with transient risk factor: 3 months 1
   • Unprovoked VTE: Consider indefinite anticoagulation 1
   • Recurrent VTE: Indefinite anticoagulation recommended 1
   • Cancer-associated VTE: Minimum 6 months, consider indefinite while cancer is active 1

3. Extended therapy with reduced dosing:

   • Apixaban: 2.5 mg twice daily after 6 months of therapeutic anticoagulation 1
   • Rivaroxaban: 10 mg once daily after 6 months of therapeutic anticoagulation 1

Practical Considerations

Monitoring Requirements

• Baseline laboratory testing: CBC, renal and hepatic function panel, aPTT, and PT/INR 1
• Follow-up: Hemoglobin, hematocrit, and platelet count every 2-3 days for first 14 days, then every 2 weeks 1
• No routine coagulation monitoring required for DOACs 1

Perioperative Management

• Discontinue DOACs before invasive procedures based on renal function and bleeding risk 1
• For high bleeding risk procedures (e.g., neuraxial anesthesia), longer interruption periods are required 1
• No need for bridging with heparin in most cases 1

Management of Bleeding

• Major bleeding on DOACs: Consider specific reversal agents (idarucizumab for dabigatran, andexanet alfa for rivaroxaban/apixaban) 4

Common Pitfalls and Caveats

1. Avoid DOACs in:

   • Mechanical prosthetic heart valves 3
   • Severe renal impairment (CrCl <15 mL/min) 1
   • Triple-positive antiphospholipid syndrome 1
   • Pregnancy (use LMWH instead) 4

2. Switching between anticoagulants:

   • When switching from parenteral to oral anticoagulants, timing is critical to avoid gaps in coverage 3
   • DOACs are NOT substitutable on a milligram-to-milligram basis 3

3. Patient adherence:

   • Shorter half-lives of DOACs make missed doses more problematic than with warfarin
   • Rivaroxaban must be taken with food for optimal absorption 5

4. Cost considerations:

   • DOACs are generally more expensive than warfarin but avoid monitoring costs 1

By following these evidence-based recommendations, clinicians can optimize the management of DVT and PE with oral anticoagulants, improving patient outcomes while minimizing bleeding risks.