DECISION MAKING ALGORITHM: ORAL ANTICOAGULANT CHOICES FOR STROKE PREVENTION IN AF

Following NHS England commissioning recommendations for national procurement for DOACs, see also the Buckinghamshire, Oxfordshire and Berkshire West (BOB) position statement for further information on prescribing
edoxaban for AF.

Warfarin as per INR to

No attain TTR >65% (see over)
Non-Valvular AF CrCl >50 ml/min CrCl 30 - 49 ml/min CrCl 15 - 29 ml/min

Warfarin as per INR to attain TTR >65%

Yes
Does the patient need a
compliance aid or have
swallowing difficulties or a
nasogastric tube?*
(see over) or choice of DOAC as
determined by the following information.
When all considerations are equal, the
Rivaroxaban 20 mg once daily or
most cost effective DOAC should be the Rivaroxaban 15 mg once daily or
Yes Apixaban 2.5 mg twice daily or
first choice. Apixaban 2.5 mg twice daily or
Edoxaban 60 mg OD (30 mg if wt Rivaroxaban 15 mg
Edoxaban 30 mg once daily
<60 kg) once daily or
Apixaban 2.5 mg twice
daily or
Does the patient have two or more Rivaroxaban 20 mg once daily or
Rivaroxaban 15 mg once daily or Edoxaban 30 mg once
of the following characteristics? Apixaban 5 mg BD or
No Apixaban 5 mg twice daily or daily
Yes Age ≥80 years, body weight ≤60 kg Edoxaban 60 mg OD (30 mg if wt
Serum creatinine Edoxaban 30 mg once daily
<60 kg)
≥133 micromol/l

Rivaroxaban 20 mg once daily or

Is the patient’s body weight Yes Edoxaban 30 mg once daily or
Yes
≤60 kg? Dabigatran 110 mg twice daily or
No Apixaban 2.5 mg twice daily Rivaroxaban 15 mg once daily or
Edoxaban 30 mg once daily or
Dabigatran 110 mg twice daily or
No Rivaroxaban 20 mg once daily or Apixaban 2.5 mg twice daily
Rivaroxaban 15 mg
Is the patient aged ≥80 years? Yes Edoxaban 60 mg once daily or once daily or
Dabigatran 110 mg twice daily or Edoxaban 30 mg once
Apixaban 2.5 mg twice daily daily or
Is the patient’s serum creatinine Apixaban 2.5 mg twice
≥133 micromol/l? Rivaroxaban 15 mg once daily or daily
No Rivaroxaban 20 mg once daily or Edoxaban 30 mg once daily or
Edoxaban 60 mg once daily or Dabigatran 110 mg twice daily or
No Dabigatran 110 mg twice daily or Apixaban 5 mg twice daily *Dabigatran additional
Apixaban 5 mg twice daily
Yes Is the patient’s serum creatinine prescribing notes
Is the patient’s body weight ≤60 kg?
≥133 micromol/l? There is an option to consider
Rivaroxaban 20 mg once daily or reducing dose of dabigatran based
Edoxaban 30 mg once daily or Rivaroxaban 15 mg once daily or on other factors. In addition to
Yes Dabigatran 150 mg twice daily or Edoxaban 30 mg once daily or patients ≥80 years, a dose reduction
Apixaban 2.5 mg twice daily *Dabigatran 150 mg twice daily or to 110 mg twice daily may be
Apixaban 2.5 mg twice daily considered if the patient has a
relative lower thromboembolic risk
See over for significant drug Rivaroxaban 20 mg once daily or combined with a high risk of
interactions and associated Edoxaban 30 mg once daily or bleeding and one or more of the
dose adjustments and No Dabigatran 150 mg twice daily or following factors:
Rivaroxaban 15 mg once daily or
monitoring requirements. Apixaban 5 mg twice daily • Age 75 - 79 years; if standard
Edoxaban 30 mg once daily or
dose is used then it should be
*Dabigatran 150 mg twice daily or
Apixaban 5 mg twice daily reduced when patient reaches
Rivaroxaban 20 mg once daily or 80 years old
Edoxaban 60 mg once daily or
No • Creatinine clearance 30 - 49
Dabigatran 150 mg twice daily or
Apixaban 5 mg twice daily ml/min
• Body weight of <50 kg
*For guidance on crushing tablets and dispersing in water, juice or puree, please refer to the full guideline (313FM Dabigatran, Rivaroxaban, Edoxaban and Apixaban for Atrial Fibrillation (AF)) • Gastritis, oesophagitis or
Adapted from “NOAC prescribing in patients with non-valvular AF” Greater Glasgow & Clyde CCG gastro-oesophageal reflux

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DOAC MONITORING GUIDANCE
Creatinine Clearance (CrCl) - Cockcroft-Gault Method – use actual body weight when calculating CrCl for DOACs (see also note below)
It is essential to calculate the patient’s creatinine clearance using the Cockcroft-Gault (CG) formula for DOAC dosing decisions using ACTUAL BODY WEIGHT ideally taken within last 6 - 12 months or more recently if
frail or likely to have been a change in weight (NOT ideal body weight). For definition of frailty see Rockwood clinical frailty scale.
There is limited data on appropriate dosing of DOACs in extremes in body weight (specialist advice should be sought for patients who weigh <45 kg or >120 kg). Actual body weight was used in clinical trials to
calculate CG equation but there was a paucity of data in the clinical trials and it may not be accurate for estimation of CrCl at extremes of bodyweight, especially in obese patients.
The use of a web based application such as MDCalc LINK 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. Where these results cross or are close to a CrCl level that may require a DOAC dose change, this can support dosing decision on the most appropriate
DOAC, taking into account stroke and bleeding risk. For further guidance and information on dosing in renal impairment see DOACs in Renal Impairment-Practice Guide to Dosing Issues (there is also a MDCalc
app available for download).

RECOMMENDED MONITORING SCHEDULE When to consider switching from warfarin to DOAC

Consider changing to one of the DOACs if:
Assess compliance and interacting drugs –at initiation AND at each review, recommended at least annually • 2 INR values higher than 5 or 1 INR value is higher than 8 within the past 6 months
− Check for side effects - at each review, recommended at least annually. • 2 unplanned INR values less than 1.5 within the past 6 months
• Time in therapeutic range (TTR) is <65% in last 12 months
− FBC and LFTs (as ALT), weight, BP and pulse check – at initiation AND at least annually • Housebound and/or requiring drugs dispensed in compliance aid by community
− Bilirubin - at initiation ONLY. pharmacy

Stroke versus bleeding risk assessment - at initiation AND at least annually Switching from warfarin to DOAC
• Discontinue warfarin and start apixaban as soon as INR is <2.5
U&Es at initiation AND as below:
• Discontinue warfarin and start dabigatran as soon as INR <2.5
CrCl >60 ml/min - annually. Consider 6 monthly if aged >75 years and frail. • Discontinue warfarin and start rivaroxaban as soon as INR ≤3.0
CrCl 30 – 60 ml/min 6 monthly • Discontinue warfarin and start edoxaban when the INR is ≤2.5
CrCl <30 ml/min 3 monthly The time taken to reach the desired INR may vary from person to person and will depend on
the individual’s initial INR level and renal function.
The European Heart Rhythm Association suggests that if CrCl is less than 60 ml/minute, the frequency of monitoring
(in months) can be guided by the CrCl divided by 10. For example, if the creatinine clearance is 34 ml/minute then
Abbreviations NB: All patients prescribed an oral
the renal function should be monitored every 3 - 4 months. More frequent monitoring if inter-current illness or
medicines that may impact on renal or hepatic function. DOAC - Direct oral anticoagulants; OAC - Oral anticoagulant require a patient safety
anticoagulants; INR - International normalised card (also known as an alert card) which
ratio; AF - Atrial fibrillation provides appropriate details of their
treatment.

Drugs with the potential to interact with DOACs - see also individual SPCs for DOACs on available on www.medicines.org.uk

The European Society of Cardiology have produced a useful practical guide on prescribing DOACs which gives useful information on the effect of drug to drug interactions and clinical factors on DOAC
drug levels – see https://academic.oup.com/eurheartj/article/39/16/1330/4942493.

Effect Interacting agent Action

Increased bleeding risk
Increased OAC exposure
Increased OAC exposure
Decreased OAC exposure
Increased bleeding risk
Theoretical increase in OAC
exposure
Changes in bioavailability
Verapamil
Ciclosporin, dronedarone, erythromycin, ketoconazole
Itraconazole, voriconazole, posaconazole, clarithromycin, HIV protease inhibitors,
Rifampicin, phenytoin, carbamazepine, levetiracetam phenobarbitone, St John’s Wort
Aspirin, clopidogrel, ticagrelor, prasugrel, dipyridamole, NSAIDs, SSRIs, SNRIs
Tacrolimus
Food
Reduce dose of dabigatran to 110 mg twice a day
Reduce dose of edoxaban to 30 mg once a day if use cannot be avoided.
Avoid combination with other OACs.
Avoid combination
Contraindicated with dabigatran and rivaroxaban (ref SPC) and combination best avoided
with apixaban and edoxaban. Can use warfarin with initial closer INR monitoring.
Caution. Avoid antiplatelet unless there is a specific indication for use.
Suggested that combination is avoided
Rivaroxaban must be taken with food. Other OACS unaffected by timing of meals.

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See also:
Guideline 34FM Dabigatran: Guidance for Management of Overdose, Bleeding and Emergency/Elective Surgery
Guideline 240FM Rivaroxaban and Apixaban: Guidance for Management of Overdose, Bleeding and Emergency/Elective Surgery
Guideline 313FM Dabigatran, Rivaroxaban, Edoxaban and Apixaban for Non Valvular Atrial Fibrillation (AF)
Guideline 775FM Treatment of Atrial Fibrillation

Title of Guideline Decision Making Algorithm: Oral Anticoagulant Choices for Stroke Prevention in AF
Guideline Number 313AFM (Appendix 2 of Guideline 313FM)
Version 1.2
Effective Date April 2021
Review Date April 2024
Amended April and June 2022
Original Version Published April 2021
Approvals:
Medicines Check (Pharmacy) 14th April 2021
Clinical Guidelines Group 20th April 2021
Authors (June 2022) Janice Craig, Medicines Optimisation Lead Pharmacist,
Buckinghamshire CCG
Roshni Kotecha, Medicines Optimisation Pharmacist, Buckinghamshire CCG
Kirsty Scott, NOAC Pharmacist BHT
Dr Renu Riat, Haematology Consultant BHT
Dr Piers Clifford, Cardiology Consultant BHT
Jane Butterworth: Associate Director Medicines Optimisation Buckinghamshire CCG
Shona Lockie: Clinical Director MMT Buckinghamshire CCG
Phil Southworth: Associate Director of Pharmacy BHT
SDU(s)/Department(s) responsible Cardiology
for updating the guideline Haematology
Pharmacy (Primary and Secondary Care)
Uploaded to Intranet 29th April 2021, 5th April and 18th July 2022
Buckinghamshire Healthcare NHS Trust/Buckinghamshire Clinical Commissioning Group

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