What are the different dosing regimens and indications for directly acting oral anticoagulants (DOACs), including apixaban (Eliquis), rivaroxaban (Xarelto), edoxaban (Savaysa), and dabigatran (Pradaxa), for conditions such as atrial fibrillation, deep vein thrombosis (DVT), and pulmonary embolism (PE) in patients with varying degrees of renal impairment?

Direct Oral Anticoagulant (DOAC) Dosing Regimens and Indications

DOACs should be selected based on indication, renal function, and bleeding risk, with apixaban generally preferred for most patients due to its superior safety profile and lower risk of gastrointestinal bleeding compared to other DOACs. 1

Apixaban (Eliquis)

Atrial Fibrillation

• Standard dose: 5 mg twice daily 2
• Reduced dose: 2.5 mg twice daily if patient has at least 2 of 3: age ≥80 years, weight ≤60 kg, or serum creatinine ≥1.5 mg/dL (133 μmol/L) 2, 3
• Severe renal impairment: 2.5 mg twice daily if CrCl 15-29 mL/min 2

DVT/PE

• Initial treatment: 10 mg twice daily for 7 days 2
• Maintenance: 5 mg twice daily 2
• Extended prevention: 2.5 mg twice daily after 6 months of initial treatment 2

VTE Prevention (Post-orthopedic surgery)

• 2.5 mg twice daily 2

Rivaroxaban (Xarelto)

Atrial Fibrillation

• Standard dose: 20 mg once daily with food 2, 3
• Reduced dose: 15 mg once daily with food if CrCl ≤50 mL/min 2

DVT/PE

• Initial treatment: 15 mg twice daily with food for 21 days 2
• Maintenance: 20 mg once daily with food 2
• Extended prevention: 10 mg once daily after 6 months of initial treatment 2

VTE Prevention (Post-orthopedic surgery)

• 10 mg once daily 2

Dabigatran (Pradaxa)

Atrial Fibrillation

• Standard dose: 150 mg twice daily 2, 3
• Reduced dose: 110 mg twice daily for patients ≥80 years, concomitant verapamil, or high bleeding risk 2
• Renal impairment: Not recommended if CrCl <30 mL/min 2

DVT/PE

• Initial treatment: Requires 5-10 days of parenteral anticoagulation before starting dabigatran 2
• Maintenance: 150 mg twice daily 2
• Outside US: 110 mg twice daily approved for DVT/PE treatment 2

VTE Prevention (Post-orthopedic surgery)

• 220 mg once daily (initial dose 110 mg 1-4 hours after surgery) 2, 4

Edoxaban (Savaysa)

Atrial Fibrillation

• Standard dose: 60 mg once daily 2, 3
• Reduced dose: 30 mg once daily if weight ≤60 kg, CrCl ≤50 mL/min, or concomitant P-gp inhibitor therapy 2

DVT/PE

• Initial treatment: Requires 5-10 days of parenteral anticoagulation before starting edoxaban 2
• Maintenance: 60 mg once daily 2
• Reduced dose: 30 mg once daily if weight ≤60 kg, CrCl ≤50 mL/min, or concomitant P-gp inhibitor therapy 2

Renal Impairment Considerations

Severe Renal Impairment (CrCl 15-29 mL/min)

• Apixaban: 2.5 mg twice daily (preferred DOAC in renal impairment due to lower renal elimination) 3
• Rivaroxaban: 15 mg once daily with food 2
• Dabigatran: Not recommended (high renal elimination) 2, 5
• Edoxaban: 30 mg once daily 2

End-Stage Renal Disease (CrCl <15 mL/min)

• All DOACs generally contraindicated; consider warfarin with INR 2.0-3.0 2

Duration of Treatment

Atrial Fibrillation

• Indefinite treatment as long as benefit outweighs bleeding risk 3

DVT/PE

• Provoked VTE: Minimum 3 months 2
• Unprovoked VTE: Extended therapy (no scheduled stop date) recommended if low bleeding risk 2
• Cancer-associated VTE: DOACs preferred over LMWH and VKA, except in GI or genitourinary malignancies where bleeding risk may be higher 2

Special Considerations

1. Perioperative Management:

   • Low bleeding risk surgery: Last dose 2 days before surgery for most DOACs 2
   • High bleeding risk surgery: Last dose 3-5 days before surgery depending on renal function 2

2. Cardioversion:

   • For AF ≥48h: At least one DOAC dose ≥4h before cardioversion (≥2h for apixaban loading dose) with TOE, or 3 weeks of anticoagulation before cardioversion 2

3. Comparative Safety:

   • Apixaban has the lowest risk of major bleeding among DOACs 1, 6
   • Apixaban is associated with lower risk of GI bleeding compared to dabigatran, edoxaban, and rivaroxaban 1

4. Common Pitfalls:

   • Failure to adjust dose based on renal function, age, weight, or drug interactions
   • Inappropriate use in mechanical heart valves (contraindicated) 3
   • Incorrect timing of initial dosing for DVT/PE (rivaroxaban and apixaban have specific loading doses) 2
   • Discontinuing due to fall risk alone (not recommended) 3

Remember to regularly monitor renal function, liver function, and complete blood count in all patients on DOACs, with more frequent monitoring (every 6 months) in elderly patients or those with renal impairment 3.