Quick reference guide to apixaban

Figures & data

Table 1 DOAC licenses and associated randomized controlled trials

DOAC	Randomized controlled trial	Licensing
Rivaroxaban	EINSTEIN DVT (rivaroxaban vs enoxaparin for DVT)^Citation19 EINSTEIN PE (rivaroxaban vs enoxaparin for PE)^Citation20 ROCKET AF (rivaroxaban vs warfarin for AF)^Citation21	Prevention of VTE in elective hip/knee surgery (10 mg OD for 35/12 days, respectively) Treatment of DVT and PE and prophylaxis after recurrent DVT/PE (15 mg BD for 21 days, then 20 mg OD) Stroke prevention in patients with AF + one CHADS2 risk factor (20 mg OD) Prevention of atherothrombotic events in adults after acute coronary syndrome (2.5 mg OD)
Dabigatran	RE-COVER (dabigatran vs warfarin for VTE)^Citation22 RE-LY (dabigatran vs warfarin in AF)^Citation2	Treatment of DVT or PE after parenteral anticoagulation for 5–10 days (150 mg BD) Stroke prevention in patients with AF + one of reduced ejection fraction/CHD/diabetes/<65 (150 mg BD) Prevention of VTE in elective hip/knee surgery (110 mg 1–4 hours after surgery, then 220 mg OD 9/7)
Apixaban	ARISTOTLE (apixaban vs warfarin in AF)^Citation5 AMPLIFY (apixaban vs enoxaparin followed by warfarin for VTE)^Citation4	Stroke prevention in patients with AF + one CHADS2 risk factor (5 mg BD) Prevention of VTE in elective hip/knee surgery (2.5 mg BD for 35/12 days, respectively) Treatment of DVT and PE (10 mg BD for 7 days, then 5 mg BD), or prophylaxis after recurrent DVT/PE (2.5 mg BD) Prevention of VTE (2.5 mg BD)
Edoxaban	ENGAGE-AF-TIMI (edoxaban to warfarin in AF)^Citation23 Hokusai VTE (edoxaban to warfarin VTE)^Citation24	Treatment of DVT or PE and prophylaxis after recurrent DVT/PE (60 mg OD) Prevention of stroke and systemic embolic events in patients with AF (60 mg OD)

Note: Bold indicates NICE license without US Food and Drug Administration license.

Abbreviations: AF, atrial fibrillation; BD, twice daily; CHADS₂, congestive heart failure, hypertension, age=75 years, diabetes mellitus, stroke (doubled); CHD, coronary heart disease; DOAC, direct oral anticoagulants; DVT, deep vein thrombosis; NICE, National Institute for Clinical Excellence; OD, once daily; PE, pulmonary embolism; VTE, venous thromboembolism.

Table 2 Pharmacokinetics of apixaban

Mode of action	Reversible and selectively inhibits free and clot bound factor Xa
Prodrug	No
Half-life	12 hours
Peak levels	1–2 hours
Doses	BD
Excretion	25% renal
Use in pregnancy/breast feeding	No
Interactions	CYP3A4 and P-GP inducers: carbamazepine, phenytoin and rifampicin – increases risk of stroke/embolism
	CYP3A4 and P-GP inhibitors: HIV protease inhibitors, itraconazole, ketoconazole and clarithromycin
CrCl 15–29 mL/min	(+Age >80 OR weight >60 kg) reduced dose (50%)
CrCl <15 mL/min	Not indicated
Weight <60 kg	(+Age >80 years or CrCl 15–29 mL/min) reduced dose (50%)
Mild hepatic impairment	Reduced dose
Moderate-to-severe hepatic impairment	Not indicated

Abbreviations: BD, twice daily; CrCl, creatinine clearance; CYP3A4, cytochrome P450 3A4; HIV; human immunodeficiency virus; P-GP, P-glycoprotein.

Table 3 Comparison of the major studies reviewed in the licensing of apixaban

Study	Comparison	Apixaban dose	Outcomes	Bleeding events	Mortality
ARISTOTLE^Citation5	Apixaban vs warfarin for stroke prevention in AF (18,201 patients)	5 mg BD	Reduced rates of stroke and/or embolism (RR=0.79)	Reduced bleeding (RR=0.67)	Reduced death rates (RR=0.89)
AMPLIFY^Citation4	Apixaban vs enoxaparin followed by warfarin for treatment of VTE (5,400 patients)	10 mg OD for 7 days followed by 5 mg for 3 months	Noninferior	Reduced bleeding (RR=0.33)	N/A
AVERROES^Citation11	Apixaban vs aspirin for stroke prevention in AF (5,599 patients)	5 mg BD	Reduced rates of stroke and embolism (RR=0.43)	Noninferior	Reduction (RR=0.80)
ADVANCE-1^Citation13	Apixaban vs enoxaparin for VTE prophylaxis post total knee replacement (3,195 patients)	2.5 mg BD	Noninferior	Reduced	N/A
ADVANCE-2^Citation14	Apixaban vs enoxaparin for VTE prophylaxis post total knee replacement (3,057 patients)	2.5 mg BD	Reduced rates of VTE (RR 0.62)	Reduced	N/A

Abbreviations: AF, atrial fibrillation; BD, twice daily; OD, once daily; VTE, venous thromboembolism; RR, relative risk; N/A, not available.

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LassenMRGallusARaskobGEApixaban versus enoxaparin for thromboprophylaxis after hip replacementN Engl J Med2010363262487249821175312

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