Please note: this guideline has exceeded its review date and is currently under review by specialists. Exercise caution in the use of the clinical guideline.

Atrial Fibrillation (AF) – Persistent

Objectives

Therapeutic:

Relieve symptoms – often only rate control required; diuretic may also be needed (often only on temporary basis).
Target ventricular (apex or ECG) rate <110bpm. If still symptomatic, aim for lower rate, <80bpm.
Assess thromboembolic risk and anticoagulate as appropriate (see flow chart further on).
In some cases, consider restoration of sinus rhythm by electrical or pharmacological cardioversion (only attempt chemical or electrical cardioversion after adequate anticoagulation; risk of thromboembolism if not anticoagulated; limited long-term success).
Optimal management of concomitant cardiovascular disease.

Diagnostic:

Exclude thyrotoxicosis.
Exclude acute (binge) or chronic alcohol consumption.
Exclude mitral stenosis and other valve problems, see below.
Determine if there are echocardiographic risk factors for stroke or thromboembolism.
Identify concomitant left ventricular (LV) systolic dysfunction and heart failure.

Essential investigations

A resting 12-lead ECG – confirms diagnosis, shows the ventricular rate, may indicate presence of structural heart disease.
Thyroid function tests
Liver enzymes if alcohol abuse is suspected.
A transthoracic echocardiogram – excludes mitral stenosis, gives structural and functional assessment of heart (e.g. whether LV systolic dysfunction / hypertrophy) and therefore helps identify need for anticoagulation.

N.B. Investigation should not delay treatment to slow the ventricular rate and reduce the risk of thromboembolism.

Ventricular rate control

Target ventricular (apex or ECG) rate <110bpm. If still symptomatic then aim for lower rate, <80bpm.
Patients without heart failure should be started on either a beta-blocker or rate-limiting calcium-channel blocker (CCB):
- Rate-limiting CCB i.e. verapamil - start with verapamil (slow release) oral 120mg once daily and titrate up to 240mg once daily if ventricular rate still >110bpm.

N.B. Beta-blockers and rate-limiting CCBs (e.g. verapamil or diltiazem) must not be combined except under specialist supervision. Check before prescribing.

Digoxin has a limited role as first-line treatment for ventricular rate control. It can be used in combination with a beta-blocker or rate-limiting CCB when control of the ventricular rate is difficult.

Patients with heart failure should be started on digoxin or beta-blocker as appropriate and follow the NHSGGC Heart Failure guideline.

Heart failure / LV Systolic Dysfunction

See NHSGGC guidelines on StaffNet. ACE inhibitors and beta-blockers are strongly recommended. Beta-blockers must be initiated under direction of a hospital physician. Rate-limiting CCBs should be avoided.

Patients to refer for specialist assessment / consideration of cardioversion

Young age (<60 years)
Reversible precipitating cause of AF (e.g. alcohol binge, thyrotoxicosis, pneumonia, recent surgery) and no major structural or functional heart disease.
Difficulty with ventricular rate control
Valve disease
LV systolic dysfunction / heart failure
AF causing symptomatic limitation despite rate-limiting treatment e.g. heart failure, excessive exertional breathlessness, undue fatigue.
Patients with atrial flutter who might be suitable for ablation.

Prevention of stroke / thromboembolism

Patients with both recurrent paroxysmal AF and sustained AF have a high risk of thromboembolism, particularly stroke. Compared to subjects without AF the absolute risk of stroke is, on average, increased by about 4-fold and the risk of stroke is about 4% per annum.
This risk is greatest in patients with certain risk factors (see flow diagram below).
For primary prevention, anticoagulants can substantially reduce risk of thromboembolism.
Patients with AF and a previous stroke or transient ischaemic attack (TIA) have an absolute risk of a further stroke of the order of 10–12% per annum and an absolute benefit of approximately 80 fewer strokes per 1000 patient years of treatment.
N.B. Patient with a suspected stroke or TIA should first be referred for rapid specialist assessment – see Management of Stroke 1 guideline .
Advanced age is not a contraindication to anticoagulation.
In patients with 'lone' AF, i.e. AF in a structurally normal heart and no other risk factors for thromboembolic disease (CHA₂DS₂-VASC = 0), no anti-thrombotic or anticoagulant therapy is recommended.

Who should receive anticoagulant therapy

Patients with clinical risk factors or echocardiographic risk factors (see flow diagram below).
Patients without contraindications to anticoagulant therapy.

Cautions / contraindications to anticoagulant therapy

Absolute contraindications include: active bleeding, pregnancy, hepatic disease associated with coagulopathy.
Relative contraindications include: significant bleeding risk e.g. active peptic ulcer or recent head injury; bleeding in the last 6 months; previous cerebral haemorrhage, stroke <14 days.
Cautions include: recurrent falls e.g. weekly, alcohol abuse.

Choice of agent: direct oral anticoagulant agents (DOACs) vs warfarin

Pros of DOACs

More stable anticoagulation
No requirement for anticoagulant monitoring
Fewer food and drug interactions
Fewer intracranial bleeds

Cons of DOACs

Specific antidote only available with dabigatran
More gastrointestinal bleeding with dabigatran and rivaroxaban, especially in the elderly.
Requirement for assessment of renal function before starting, and dose adjustments in renal impairment.

Remember: DOACS are indicated only in those patients who have non-valvular AF; not those with mitral stenosis or a mechanical valve. Patients with tissue valve or mitral valve repair can still be considered for DOAC.

Combined anticoagulant and antiplatelet therapy

Adding aspirin to warfarin in AF does not reduce the risk of stroke (except with prosthetic heart valves) but substantially increases the risk of bleeding. The combination is generally not indicated in stable coronary disease, but there are some circumstances, such as after an acute coronary event or PCI, when short-term combined double or triple therapy is used according to cardiologist advice.

Table 1 – CHA₂DS₂-VASC scoring table

CHA₂DS₂-VASC	Score
CHF	1
Hypertension	1
Age ≥75	2
Diabetes Mellitus	1
Stroke / TIA / thromboembolism	2
Vascular disease (PVD, IHD)	1
Age 65 – 74	1
Female	1 (only if other risk factors)
Lip GHY et al. CHEST 2010; 137(2): 263 – 272. Adapted with permission from the American College of Chest Physicians.

Figure 1 – Prevention of stroke / thromboembolism in AF stroke algorithm

Non-valvular Atrial fibrillation (paroxysmal, persistent or permanent)

↓

Determine risk of thromboembolism (use CHA₂DS₂-VASC, table 1 above)

↓

CHA₂DS₂-VASC = 0 – No anticoagulant needed

CHA₂DS₂-VASC = 1 – consider warfarin or DOAC (edoxaban preferred) after discussion of risk and patient preference

CHA₂DS₂-VASC >1 - warfarin or DOAC (edoxaban preferred)

↓

Consider switching from warfarin to DOAC (edoxaban preferred) if TTR <65% (despite good concordance)

Initiation and monitoring of warfarin therapy

Urgent anticoagulation required – use the Age-adjusted warfarin induction regimen and cover with enoxaparin (see NHSGGC StaffNet / Clinical Info / Clinical Guidelines Directory and search for 'warfarin induction protocols').

Anticoagulation not urgent – consider a slower regime such as low-slow-start warfarin. Details available on NHSGGC StaffNet / Clinical Info / Clinical Guidelines Directory and search for 'warfarin induction protocol for out-patients'. This regime involves 2mg being given daily for 2 weeks with once weekly monitoring. Contact anticoagulation pharmacist if more information is required (see Appendix 6 under GCAS for contact details).

Direct oral anticoagulant agents

Edoxaban (preferred formulary choice) oral 60mg once daily if creatinine clearance (CrCl) >50ml/minute. Reduce dose to 30mg once daily if:

CrCl 15-50ml/minute or
<60kg or
Concomitant use of the folowing P-gp inhibitors: ciclosporin, dronedarone, erythromycin, ketoconazole.

For further edoxaban prescribing advice see the manufacturer's summary of product characteristics or the DOAC Prescribing in Patients with Non-Valvular AF: Frequently Asked Questions document available at www.ggcmedicines.org.uk. To calculate CrCl use the calculator available within the GGC Medicines App or on NHSGGC StaffNet / clinical info.

Other DOACs include:

Apixaban oral 5mg twice daily
Dabigatran oral 150mg twice daily
Rivaroxaban oral 20mg once daily

Doses may need to be reduced in some patients who have either low body weight (≤60kg), renal impairment or age ≥80 years and another risk factor. For details see DOAC Prescribing in Patients with Non-Valvular AF: Frequently Asked Questions document available at www.ggcmedicines.org.uk. Many contraindications to warfarin also apply to the newer agents.

N.B. DOACs are only indicated as an alternative to warfarin in non-valvular atrial fibrillation patients, and should not be used as an alternative to warfarin in patients with prosthetic valves.

Drugs for atrial fibrillation

For an overview of the management of AF – Persistent see above under 'Therapeutic', and for Recent Onset AF and Flutter see here.

Anticoagulation

For choice see guidance above. Note: on the recommendation of GCAS, the choice of oral anticoagulant may change for selected patient groups.

Chemical cardioversion

Amiodarone

For chemical cardioversion (see IV or oral dosing guidance in Recent onset AF and flutter guideline).

N.B. Ideally, check baseline thyroid and liver function tests before starting. Interactions include digoxin and simvastatin (see BNF Appendix 1 for more details).

Rate control

Beta-blockers

See above for dosing guidance.

Digoxin

In frail elderly patient or patients with very low body weight, lower loading and maintenance doses than those advised below may be required. If further advice is required then contact your clinical pharmacist, or Medicines Information (see Appendix 6 for contact details) or out-of-hours the on-call pharmacist.

Loading dose – normal renal function:

Digoxin oral (preferred route) 500micrograms followed 6 hours later by 500–1000micrograms in divided doses > 6 hours apart or
Digoxin IV 500micrograms followed 6 hours later by 250–500micrograms in divided doses 4–6 hours apart.

Loading dose – renal impairment (creatinine clearance <30ml/minute):

Digoxin oral (preferred route) 500micrograms followed 6 hours later by 250–375micrograms in divided doses >6 hours apart or
Digoxin IV 250–500micrograms

N.B. Digoxin injection: 25micrograms = 0.1ml. Additional loading doses may be required; give according to ventricular (heart rate) response.

Maintenance daily dose: The tables below outline digoxin daily maintenance dosing for patients <60kg (see table 2) and >60kg (see table 3).

Table 2 – Digoxin daily maintenance dose if <60kg

CrCl*	Oral	IV
>50ml/min	250–312.5micrograms	175–200micrograms
20–50ml/min	125–187.5micrograms	100micrograms
<20ml/min	62.5–125micrograms	50–75micrograms
*Creatinine clearance - use the CrCl calculator in the GGC Medicines App, or on NHSGGC StaffNet / Clinical Info section or use the equation here

Table 3 – Digoxin daily maintenance dose if >60kg

CrCl*	Oral	IV
>50ml/min	250–375micrograms	175–250micrograms
20–50ml/min	187.5micrograms	125micrograms
<20ml/min	62.5–125micrograms	50–75micrograms
*Creatinine clearance - use the CrCl calculator in the GGC Medicines App, or on NHSGGC StaffNet / Clinical Info section or use the equation here

Target concentration range: 0.5–2micrograms/L (6–24 hours after the dose)

Time to steady state: 5–10 days

Concentration increased by amiodarone, diltiazem, quinine, verapamil (see BNF Appendix 1 for more details).

Last reviewed April 2018