DIRECT ORAL ANTICOAGULANTS (DOACs)

1. CLASSIFICATION & MECHANISM

 2. PHARMACOKINETICS 

 ICU Pearl

• Dabigatran = highly renal dependent → avoid in AKI
• Apixaban = safest in renal dysfunction

 3. INDICATIONS 

 Strong Indications (ESC / ACC / CHEST)

• Non-valvular atrial fibrillation (NVAF) → stroke prevention
• Venous thromboembolism (VTE):
• DVT
• PE
• Extended VTE prophylaxis

 NOT recommended in:

• Mechanical valves
• Moderate–severe mitral stenosis
• Pregnancy

 4. ICU RELEVANCE

Common ICU Scenarios

• AF in ICU patient
• VTE prophylaxis/treatment
• Transition from heparin to oral therapy

 Problems in ICU

• Unpredictable absorption (ileus, NG feeds)
• Organ dysfunction (renal/hepatic)
• Drug interactions (antifungals, antivirals)
• Procedures & bleeding risk

 Hence:
➡️ DOACs are often withheld in unstable ICU patients
➡️ Prefer UFH infusion (reversible, titratable)

• Dabigatran → only dialyzable DOAC
• Apixaban → best in renal failure
• Rivaroxaban → must be taken with food

 5. DOSING

 Apixaban

• AF: 5 mg BD
• Reduce to 2.5 mg BD if:
• Age ≥80
• Weight ≤60 kg
• Creatinine ≥1.5

 Rivaroxaban

• AF: 20 mg OD (with food)
• 15 mg OD if renal impairment

 Dabigatran

• AF: 150 mg BD
• 110 mg BD (elderly / bleeding risk)

 6. RENAL ADJUSTMENT 

 Dabigatran = highest accumulation risk

7. MONITORING

 Routine monitoring NOT required

BUT in ICU:

 8. BLEEDING & REVERSAL 

 Specific Antidotes

 If antidote NOT available

• PCC (4-factor)
• Activated charcoal (early ingestion)
• Hemodialysis → ONLY for dabigatran

9. DRUG INTERACTIONS

 Avoid with:

• Strong CYP3A4 inhibitors:
• Azoles (e.g., voriconazole)
• Protease inhibitors
• P-gp inhibitors:
• Amiodarone
• Verapamil

 ↑ bleeding risk