What are the initial dosing recommendations for Direct Oral Anticoagulants (DOACs) and heparin in patients with atrial fibrillation, deep vein thrombosis, or pulmonary embolism?

Initial Dosing Recommendations for Anticoagulants in Specific Conditions

For patients with atrial fibrillation, deep vein thrombosis, or pulmonary embolism, direct oral anticoagulants (DOACs) are preferred over vitamin K antagonists due to their fixed dosing regimens, no need for laboratory monitoring, and lower risk of major bleeding. 1

Venous Thromboembolism (DVT/PE) Treatment

Initial Treatment Options:

• Apixaban: 10 mg orally twice daily for the first 7 days, followed by 5 mg orally twice daily for the remainder of treatment 2
• Rivaroxaban: 15 mg orally twice daily with food for the first 21 days, followed by 20 mg daily with food 2
• Dabigatran: 150 mg orally twice daily, but must be preceded by 5-10 days of parenteral anticoagulation (heparin/LMWH) 2
• Edoxaban: 60 mg orally once daily, but must be preceded by at least 5-10 days of parenteral anticoagulation (heparin/LMWH) 2
• Warfarin (VKA): Target INR 2.0-2.5, with bridging using parenteral heparin initially 2

Parenteral Options:

• Unfractionated Heparin (IV):

  • Initial dose: 80 units/kg IV bolus (or 5,000 units), followed by continuous infusion of 18 units/kg/hour (or 20,000-40,000 units/24 hours) 3
  • Alternatively, intermittent IV dosing: Initial 10,000 units, followed by 5,000-10,000 units every 4-6 hours 3
  • Adjust dose based on aPTT monitoring (target 1.5-2.5× control) 3

• Enoxaparin (LMWH):

  • Standard treatment dose: 1 mg/kg subcutaneously twice daily or 1.5 mg/kg once daily 2
  • For cancer-associated thrombosis: Same dosing as above 2

• Dalteparin (LMWH for cancer patients):

  • 200 units/kg subcutaneously once daily for 1 month, then 150 IU/kg subcutaneously once daily (months 2-6) 2

Atrial Fibrillation (Stroke Prevention)

• Apixaban: 5 mg orally twice daily; reduce to 2.5 mg twice daily if patient has at least 2 of the following: age ≥80 years, weight ≤60 kg, or serum creatinine ≥1.5 mg/dL 2
• Dabigatran: 150 mg orally twice daily; consider 110 mg twice daily if age ≥80 years, concomitant verapamil, or increased risk of GI bleeding (note: 110 mg dose not available in US) 2
• Edoxaban: 60 mg orally once daily; reduce to 30 mg once daily if weight ≤60 kg, CrCl ≤50 mL/min, or concomitant therapy with strong P-gp inhibitor 2
• Rivaroxaban: 20 mg orally once daily with food; reduce to 15 mg once daily if CrCl ≤50 mL/min 2

Special Considerations

Renal Function:

• Severe renal impairment (CrCl 15-29 mL/min):
  • Apixaban: Standard dosing can be used 4
  • Rivaroxaban: Reduce to 15 mg once daily for AF; use with caution for VTE 5
  • Dabigatran: Not recommended if CrCl <30 mL/min 2
  • Edoxaban: Reduce to 30 mg once daily 2

Cancer-Associated Thrombosis:

• DOACs are now preferred over LMWH for most cancer patients with VTE 1
• For patients with gastric or gastroesophageal lesions, LMWH may be preferred due to lower risk of GI bleeding 1

Cardioversion for Atrial Fibrillation:

• If AF duration <48 hours: Single dose of DOAC 2-4 hours before cardioversion may be sufficient 2
• If AF duration ≥48 hours: Anticoagulate for at least 3 weeks before cardioversion or perform TEE to rule out thrombus 2

Duration of Treatment

• Minimum 3-month treatment for all patients with acute VTE who don't have contraindications to anticoagulation 1
• Extended anticoagulation recommended for:
  • Unprovoked VTE or VTE with persistent risk factors 1
  • Active cancer (if bleeding risk is not high) 1
  • Atrial fibrillation based on CHA₂DS₂-VA score (≥2 points: anticoagulation recommended; 1 point: consider anticoagulation) 2

Secondary Prevention After Initial VTE Treatment

After completing initial treatment (≥6 months), reduced doses can be considered:

• Apixaban: Either continue 5 mg twice daily or reduce to 2.5 mg twice daily 2
• Rivaroxaban: Either continue 20 mg daily or reduce to 10 mg daily 2

Common Pitfalls and Caveats

• Premature discontinuation of anticoagulants increases risk of thrombotic events; consider coverage with another anticoagulant if stopping for reasons other than bleeding 5
• Bridging with LMWH when switching to VKA should be reserved for patients at very high risk of recurrent VTE (e.g., those within 3 months of a VTE) 2
• Spinal/epidural hematoma risk with neuraxial procedures; follow specific timing recommendations for holding anticoagulants 5
• Drug interactions can significantly affect DOAC levels; always check for potential interactions 2
• Apixaban appears to have a lower risk of GI bleeding compared to other DOACs while maintaining similar efficacy for stroke prevention 6, 7