TAM guideline: Warfarin

**CHA₂DS₂VAScscoring

⁺Cardioversion: Consider restoration of sinus rhythm in patients in atrial fibrillation for less than 1 year where there is no significant structural heart disease. In asymptomatic patients over 65 years of age there is no justification in restoring sinus rhythm. Elective anticoagulation with edoxaban, apixaban dabigatran, rivaroxaban or for 4 weeks prior to direct current cardioversion is required unless the patient is already well established on warfarin. Continue anticoagulation for at least 1 month after cardioversion as the recurrence rate and embolic risk extend into the period after restoration of sinus rhythm. Patients with risk factors for thromboembolism should remain on an anticoagulant (preferably warfarin) indefinitely even if sinus rhythm is restored. Otherwise, discontinue oral anticoagulant one month post-cardioversion if ECG shows sinus rhythm.

Edoxaban⁺ prescribing information – see SPC

Dose:
60mg once daily

or
30mg once daily if one or more of:

• creatinine clearance*** 15 to 50mL/min
• body weight less than or equal to 60kg
• concomitant use of erythromycin, ciclosporin, ketoconazole, dronedarone

Avoid if creatinine clearance*** less than 15mL/min.

Apixaban⁺ prescribing information – see SPC
Dose:

• 5mg twice daily or
• 2·5mg twice daily if 2 out of (age over 80 years, body weight less than 60kg, creatinine greater than 133micromol/L)or
• 2·5mg twice daily if creatinine clearance*** 15 to 29mL/minute.

Rivaroxaban⁺prescribing information – see SPC
Dose:

• 20mg once daily (no dosage adjustment required for age)
• if creatinine clearance*** 15 to 49 mL/min reduce dose to 15mg once daily
• avoid if creatinine clearance*** less than 15mL/min
• to be taken with food.

Dabigatran⁺ prescribing information – see SPC
Dose:

• 150mg every 12 hours (or 110mg every 12 hours following individual assessment when thromboembolic risk is low and bleeding risk is high). Avoid if creatinine clearance*** less than 30mL/min/m².
• 80 years or over, 110mg every 12 hours.
• in patients receiving concomitant verapamil, reduce the dabigatran dose to 110mg every 12 hours.
• patient must be able to swallow capsule whole before prescribing.
• unsuitable for storage in monitored dosage systems (MDS).

Contra-indications: many contra-indications to warfarin therapy will also apply to edoxaban, apixaban, dabigatran and rivaroxaban, eg high bleeding risks, coagulation disorders, non-compliance and, for dabigatran only, liver enzymes 2 or more times the upper limit of normal.

Renal function: monitor renal function before starting edoxaban (see SPC), apixaban (see SPC), dabigatran (see SPC), rivaroxaban (see SPC) and at least annually.

Elderly: take particular caution especially in the frail elderly where adverse events are higher for almost all medication.

Initiating warfarin: LMWH is not usually required to cover slow initiation of warfarin.

Moving from warfarin: stop warfarin and wait until:

• INR is less than or equal to 2·5 prior to starting edoxaban
• INR is less than 2 prior to starting apixaban or dabigatran
• INR is 3 or less prior to starting rivaroxaban.

This will often be between 2 to 3 days depending on initial INR.

For patients who fail to achieve more than 60% time in therapeutic range on warfarin, consider switching to edoxaban or another DOAC if no contra-indication is present.

***see Cockroft and Gault creatinine clearance calculator.