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Home Formulary 2.0 Cardiovascular System 2.8 Anticoagulants and protamine 2.8.2 Oral anticoagulants 2.8.2.1 Atrial fibrillation

2.8.2.1 Atrial fibrillation

Prophylaxis of Stroke and Systemic Embolism in Non-valvular* Atrial Fibrilliation (AF)

ChoiceDrugDosage
1st choice

Apixaban

See table below

2nd choicesDabigatranSee table below
Or
EdoxabanSee table below
Or
Rivaroxaban
See table below
Or
Warfarin tablets 1mg, 3mgAs per INR

*Patients with mechanical valves or significant mitral valve stenosis are excluded from this treatment protocol

Doses of DOACs in renal impairment
(reduce dose in renal impairment based on Cockcroft Gault calculation of CrCl. Do not use estimated GFR)
DrugCreatinine Clearance
≥ 50 ml/min30-49 ml/min15-29 ml/min<15ml/min
Apixaban5 mg twice daily
Reduce to 2.5 mg twice daily in patients with two or more of the following characteristics:
-  Age ≥80 years
- Body weight ≤60kg
- Serum creatinine ≥1.5mg/dL (133 micromoles/L)		Reduce dose to 2.5mg twice dailyDo not use
DabigatranUsual dose is 150mg twice daily
Consider reducing to 110mg twice daily in patients aged 75-80years, or with moderate renal impairment, gastritis/ GORD or at increased risk of bleeding
Always reduce to 110mg twice daily in patients >80 years or if taking verapamil		Do not useDo not use
Edoxaban60mg once daily
Reduce to 30mg edoxaban once daily in patients with one or more of the following clinical factors:
-    Low body weight <60kg
-    Concomitant use of ciclosporin, dronedarone, erythromycin or ketoconazole		30mg once dailyDo not use
Rivaroxaban20 mg once daily with foodReduce dose to 15mg daily with foodDo not use

SPS

Prescribing Notes

  • Refer to NICE NG196 Atrial Fibrillation: diagnosis and management
  • Apixaban is recommended as first choice DOAC for AF where this is clinically appropriate
  • Warfarin is recommended where DOACs are contraindicated, not tolerated or not suitable in patients with AF. This includes:
    • Patients with mechanical prosthetic valves or significant mitral stenosis
    • Patients with severe renal dysfunction (CrCl<15mL/min)
  • Patients at extremes of body weight (i.e. <50kg or >120kg) have been under-represented in DOAC clinic trials. Refer to EHRA guidance. Small retrospective trials have reported similar efficacy and safety for DOAC vs warfarin in obese patients up to 150kg but warfarin is generally preferable >150kg (BMI approximately 50kg/m2)
  • Calculating creatinine clearance (CrCl) for DOACs:
    • CrCl calculators embedded within GP IT systems do not give a reliable estimate of CrCl for the adjustment of DOAC doses and are not recommended
    • The use of a web based application such as MDCalc is suggested where actual bodyweight is used to calculate the CG CrCl. If in addition the patient’s height is added the different weight method calculations (modified for body weight) can be seen giving a range of possible values for CrCl. Refer to DOAC dosing in renal impairment SPS guide for further details
  • The anticoagulant effect of DOACs fades rapidly 12-24 hours after the last intake. Therefore strict compliance by the patient is crucial for adequate protection. In contrast, the anticoagulant effect of warfarin persists for several days after the last warfarin dose.
  • Vitamin K (phytomenadione) can be given to reverse the effects of warfarin but takes 6-12 hours to become effective. If rapid reversal of warfarin is required specialist haematological advice on the agreed regional policy should be sought. Also refer to the BNF.
  • Specialist haematological advice should be sought regarding strategies for the reversal of the anticoagulant effects of DOACs. Specific reversal agents for dabigatran (idarucizumab) and the factor Xa inhibitors apixaban and rivaroxaban (andexanet alfa▼) are now available. These are for hospital only use – see Managed Entry Decisions for further details on when they can be used. For information on the management of bleeding complications see ‘EHRA Practical Guide to NOAC use in AF’.
  • Renal function should be monitored at initiation and at least annually for patients taking DOACs. Ensure any necessary dose reductions are made. Refer to DOAC dosing in renal impairment SPS guide for further details.
  • Refer to EHRA guidance (section 4) for information on switching between anticoagulant regimens.
  • Clinical Knowledge Summaries provide a comprehensive overview in relation to oral anticoagulation and includes information that patients should be given prior to treatment and monitoring that should be carried out.
  • Anticoagulation should not be withheld solely because of a person’s age or their risk of falls.
  • Only warfarin 1mg and 3mg tablets should be prescribed.
  • Indication and duration of treatment should be clearly recorded at initiation of treatment, the patient-held anticoagulant treatment booklet should be used. See BNF for details.
  • Patients should be warned of the hazards of treatment with anticoagulants. In particular, they should be aware of the need to report symptoms such as bruising. Anticoagulant treatment cards must be carried by patients and can be ordered by e-mailing the HSC Business Services Organisation at pharmacystationeryorders@hscni.net.
  • Dabigatran capsules cannot be crushed or opened and cannot be used in standard compliance aids due to the instability of the drug.
  • Guidance on the management of dental patients taking anticoagulants or antiplatelet drugs by the Scottish Dental Clinical Effectiveness Programme (SDECP) has been adopted for use in Northern Ireland and is available at http://www.sdcep.org.uk.

Cautions

  • A lower initial loading dose of warfarin is recommended in patients aged over 70 years.
  • There are many clinically important interactions with warfarin, clinicians are strongly advised to consult BNF before prescribing.
  • The MHRA Drug Safety Update June 2020 reminds healthcare professionals of the bleeding risk with DOACs and of the importance that patients receive an appropriate dose based on renal function.
  • DOACs are contraindicated in the setting of mechanical (metallic) valves. They may be used in bioprosthetic valves after 3 months post operatively. This is in line with EHRA guidance (see Table 1); recommendations in SPC may differ.
  • DOACs are contraindicated in the setting moderate to severe mitral stenosis but may be used with other native valvular disease. (See EHRA guidance 2018, table 1).
  • Refer to BNF for full details of cautions, contraindications and interactions with DOACs .

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