Apixaban 💊

💊 Apixaban is a direct oral anticoagulant (DOAC) used to prevent stroke and systemic embolism in non-valvular atrial fibrillation (AF) with additional risk factors (previous stroke/TIA, CCF, age >75, diabetes, hypertension). ⚠️ Always check the BNF link here for the most up-to-date prescribing guidance.

📖 About

• Direct Factor Xa inhibitor → blocks clot formation at a key step of the coagulation cascade.
• Metabolised mainly by CYP3A4.
• Oral, fixed dose, no INR monitoring needed ✅.
• Well-studied in large RCTs vs warfarin and aspirin.

📊 Landmark Trials

• ARISTOTLE trial: Apixaban vs Warfarin → lower bleeding, reduced stroke/systemic embolism, and lower mortality.
• AVERROES trial: Apixaban vs Aspirin → significant reduction in stroke/systemic embolism without a big rise in major bleeding.

📌 Indications & Dosing

• Non-valvular AF: - Standard: 5 mg BD. - Reduce to 2.5 mg BD if ≥2 of: age ≥80, weight ≤60 kg, creatinine ≥133 μmol/L.
• DVT/PE treatment: 10 mg BD for 7 days, then 5 mg BD for at least 3 months. For extended prevention of recurrence after 6 months of treatment: 2.5 mg BD.
• VTE prophylaxis post-op: - Knee replacement: 2.5 mg BD for 14 days, start 12–24h post-op. - Hip replacement: 2.5 mg BD for 35 days, start 12–24h post-op.

🔄 Interactions

• Avoid with strong CYP3A4 and P-gp inhibitors (ketoconazole, itraconazole, posaconazole, HIV protease inhibitors).
• Reduced effect with enzyme inducers: Carbamazepine, Phenytoin, Rifampicin, St John’s Wort, Dexamethasone.
• Increased bleeding risk with: warfarin, other anticoagulants, antiplatelets, NSAIDs.

⚠️ Cautions

• High HAS-BLED score or poorly controlled hypertension.
• Other anticoagulants or coagulopathy → ↑ bleeding risk.
• Stop 48h before surgery (if high bleeding risk) or 24h (if low bleeding risk).
• Avoid in pregnancy and breastfeeding.

🚫 Contraindications

• Active, clinically significant bleeding, or a lesion at significant risk of major bleeding (recent GI ulcer, malignancy, recent brain/spinal/eye surgery, intracranial haemorrhage, oesophageal varices, vascular malformations).
• Hepatic disease with coagulopathy and clinically relevant bleeding risk.
• Concomitant treatment with any other anticoagulant (except when switching or with UFH to keep a line patent).
• Prosthetic mechanical heart valves (not studied/not recommended).
• Antiphospholipid syndrome, especially triple-positive - DOACs are not recommended (MHRA 2019).
• Creatinine clearance <15 mL/min or dialysis: not recommended.

🫘 Renal Dosing (AF)

• CrCl 15–29 mL/min: 2.5 mg twice daily.
• Use creatinine clearance (Cockcroft–Gault, actual body weight) - not eGFR - for DOAC dosing decisions.

🧪 Monitoring

• Baseline FBC, U&E/creatinine clearance, LFTs, clotting screen and weight.
• Renal function at least annually; every 6 months if aged ≥75 or frail, and every 3 months if CrCl is 30–60 mL/min (rule of thumb: CrCl ÷ 10 = months between checks).
• Adherence, bleeding, falls and interacting drugs at each review.

💥 Side Effects

• Bleeding (epistaxis, GI, haematuria, gingival, bruising, menorrhagia) - the main adverse effect.
• Anaemia, nausea, raised transaminases, rash, hypotension.
• Rare: intracranial haemorrhage, hypersensitivity.

🚑 Reversal

• Stop apixaban; supportive measures; activated charcoal if ingested within ~2–6 hours.
• Life-threatening bleeding: andexanet alfa (NICE TA697: life-threatening GI bleeding) or prothrombin complex concentrate per local protocol; involve haematology.

📚 References

• BNF: Apixaban
• NICE NG196: Atrial fibrillation: diagnosis and management
• NICE NG158: Venous thromboembolic diseases
• MHRA (2019): DOACs - not recommended in antiphospholipid syndrome