DIRECT ORAL ANTICOAGULANTS (DOACs)

DIRECT ORAL ANTICOAGULANTS (DOACs)

1. CLASSIFICATION

Two classes

NOAC = Non-vitamin K antagonist oral anticoagulant.(Older terminology for DOAC)

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

2. Major advantages over warfarin

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(Classic trial:RE-ALIGN)
• Moderate–severe mitral stenosis(INVICTUS trial)
• Pregnancy(For therapeutic anticoagulation in pregnancy, LMWH is generally preferred.)
• DOAC use should generally be avoided or carefully individualized in advanced hepatic dysfunction, especially significant hepatic coagulopathy.

4. ICU RELEVANCE

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

Dabigatran and dyspepsia

• A characteristic adverse effect:Dyspepsia
• Because the formulation has an acidic core.
• Rivaroxaban → food improves absorption of higher doses.

 5. DOSING

 Apixaban

• Atrial Fibrillation : 5 mg BD
• Reduce to 2.5 mg BD if:at least 2 of the following 3 are present:
• Age ≥80
• Weight ≤60 kg
• Creatinine ≥1.5 mg/dL

Apixaban for acute VTE

Typical regimen:10 mg BID × 7 days then:5 mg BID

For extended secondary prevention:2.5 mg BID

after at least 6 months of treatment in appropriate patients.

 Rivaroxaban

• AF: 20 mg OD (with food)
• 15 mg OD if renal impairment,Dose must be based on CrCl, not simply eGFR.

Rivaroxaban for acute DVT/PE

Typical regimen:15 mg BID × 21 days followed by:20 mg OD

For extended prevention after initial treatment:

10 mg OD may be used in appropriate patients.

Edoxaban

Direct factor Xa inhibitor.

For acute VTE:Edoxaban requires initial parenteral anticoagulation.

Typically:LMWH/UFH → edoxaban

Edoxaban dosing

Typical AF dose:60 mg once daily

Reduce to:30 mg once daily

when relevant criteria such as:

• reduced CrCl
• low body weight
• certain P-gp inhibitors

are present according to labeling.

Edoxaban has a “too-good kidney function” problem in AF:

If CrCl >95 mL/min, US labeling recommends avoiding edoxaban for AF because of increased ischemic stroke compared with warfarin in ENGAGE AF-TIMI 48.

 Dabigatran

• Atrial Fibrillation : 150 mg BD
• Dose reduction may be required depending on renal function, age, bleeding risk, and local labeling.

6. RENAL ADJUSTMENT 

 Dabigatran = highest accumulation risk

7. MONITORING

 Routine monitoring NOT required

BUT in ICU:

When should DOAC levels be considered?

Examples:

• Life-threatening bleeding
• Emergency surgery
• Suspected overdose
• Severe renal dysfunction
• Unexpected thrombosis
• Suspected nonadherence
• Extremes of body weight in selected circumstances
• Drug interaction
• Uncertain timing of last dose

 8. BLEEDING & REVERSAL 

 Specific Antidotes

 If antidote NOT available

• PCC (4-factor)-50 U/kg IV
• 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

DOAC + antiplatelet therapy

Combination increases bleeding.Examples:

• DOAC + aspirin
• DOAC + clopidogrel
• DOAC + DAPT

Therefore:

Avoid unnecessary antiplatelet therapy in anticoagulated patients.

After PCI in AF, combination therapy may be required temporarily, but modern strategies generally minimize duration of triple therapy because of bleeding risk.