Arrhythmias and Anticoagulation

Faiza Khan and Zahraa Jalal

Objectives

• Understand the different types of Arrhythmias

• Identify the risk factors and symptoms of AF

• Describe the different classifications of AF and the aim of treatment

• Explain the rate and/or rhythm control treatment options

• Discuss the contraindications, adverse effects and monitoring

associated with the medicines used to manage AF

• Outline the role of antithrombotic therapy in AF, including the

risk/benefit of anticoagulants

• Briefly outline the place of the new oral anticoagulants in the

management of AF

Electrical conduction of the Heart

Arrhythmias – Definition

“Arrhythmia

Is a term which refers to any change

in the normal rate or rhythm of the heart”

Why do they occur?

•Arrhythmias develop by one of two mechanisms:

– Altered impulse generation, for example, changes in the

automaticity (ability to generate electrical impulses spontaneously

leading to depolarisation) of the pacemaker cells in the SA node, or

through the occurrence of action potentials from sites other than

the SA node

– Altered impulse conduction, for example, complete or partial block

of conduction pathways within the myocardium

Types of Arrhythmias Bradycardias Tachycardias Atrial Flutter and Atrial

Fibrillation

Heart rate of <60 beats per

min

Heart rate > 100 beats per

minute

Atrial flutter occurs less

frequently than AF, but the

two often have similar

underlying causes

If heart rate slows but

rhythm unchanged known

as sinus bradycardia

1) Supra-ventricular

tachycardias, which are

arrhythmias that arise

above the level of the

ventricles either within

the atria

2) Ventricular

tachycardias, which

arise within the

ventricles themselves

The rapid atrial rate and

disturbance of conduction

pathways in atrial flutter

increases the risk of

localised thrombus

formation and secondary

embolic events

(i.e, thrombotic stroke)

Bradycardias may also be

caused by heart block

Sinus tachycardia occurs if

the heart rate increases but

the rhythm remains

unchanged

Atrial fibrillation is the most

common type of

arrhythmias

Atrial Fibrillation - Statistics

• Roughly 1% of population

• 3-6% of patients acutely admitted to hospital have AF

• Rare before 50, prevalence doubles with each decade

after this age with a 4% prevalence after 65 yrs of age

• Nearly 10% of population over 80 yrs of age

• Patients with AF are 5 times more likely than general

population to have a stroke

– More severe

– Associated with greater disability

• Three times more likely to develop congestive heart failure

Risk factors

• Hypertension

• Coronary artery

disease

• Valve disease

• Hyperthyroidism

• Male

• Increasing age

• Obesity

• Acute MI

• Diabetes

• Heart failure

• Alcohol

• Caffeine

• Stress

• Cardiac surgery

• Pneumonia

• Pulmonary embolism

AF - Symptoms

• Can be asymptomatic

• Breathlessness

• Light-headedness

• Fatigue

• Palpitations- describing their heart as racing, pounding or

thumping in their chest

• Chest pain

• In more severe cases, patients may present with heart

failure, angina and syncope or the first presentation may

be with a related thromboembolic event

Classification of drug

Mechanism of action Comment

IA Na+ channel blocker Slows phase 0

Depolarization in ventricular muscle fibers

IB Na+ channel blocker Shortens phase 3 repolarization in ventricular muscle fibers

IC Na+ channel blocker Markedly slows phase 0 depolarization in ventricular muscle fibers

II Beta-adrenoreceptor blocker Inhibits phase 4 depolarization in SA and AV node

III K+ channel blocker Prolongs phase 3 repolarization in ventricular muscle fibers

IV Ca+ channel blocker Inhibits action potential in SA and AV nodes

Anti arrhythmic Drugs

Diagnosis

• ECG – May need 24 hour tape to rule out paroxysmal AF

• ECHO

• TFTs

• Chest X-ray

• U&Es

• Troponin

Types of AF

Paroxysmal Atrial Fibrillation

•In paroxysmal atrial fibrillation (AF), the faulty electrical signals and rapid

heart rate begin suddenly and then stop on their own. Symptoms stop

within about a week, but usually in less than

24 hours.

Persistent Atrial Fibrillation

•Persistent AF is a condition in which the abnormal heart rhythm

continues for more than a week. It may stop on its own, or it can be

stopped with treatment.

Permanent Atrial Fibrillation

•Permanent AF is a condition in which a normal heart rhythm can't be

restored with treatment. Both paroxysmal and persistent AF may become

more frequent and, over time, result in permanent AF.

Rhythm vs Rate control

Rhythm

• Rhythm control

candidates

– Symptomatic

– Under 65

– First episode of AF

– AF secondary to a treated

factor

– Have congestive heart

failure

Rate

• Rate control candidates

– Over 65

– Coronary artery disease

– Contraindications to

antiarrhythmic medication

– Unsuitable for

cardioversion

Rate control versus Rhythm control

Rate control:

• Arrhythmia allowed to

continue

slow down the increased

ventricular rate →

symptomatic improvement

drugs less s/e or toxicity

• Risk of thromboembolism

persists.

Rhythm control:

• Aims to restore SR

• Improves: exercise tolerance, CO,

avoids cardiomyopathy and relieves

symptoms

• Unclear whether more effective than

rate control at reducing symptoms or

improving survival and reducing the

risk of embolism/stroke

• Drugs used can cause serious

proarrhythmia.

AF - Acute Management

Rate control Beta-blocker eg. IV metoprolol 5mg slow bolus

Ca-channel blocker, eg. verapamil 5-10mg slow bolus

Amiodarone

Digoxin (slow onset of action, even if IV)

Rhythm control

IV amiodarone, 300mg over 1hr followed by 24hr infusion

Other drugs: flecainide

Rate control-guidelines

• Offer rate control as the first-line strategy to

people with atrial fibrillation, except in people:

– whose atrial fibrillation has a reversible cause

– who have heart failure thought to be primarily caused

by atrial fibrillation

– with new-onset atrial fibrillation

– with atrial flutter whose condition is considered suitable

for an ablation strategy to restore sinus rhythm

– for whom a rhythm control strategy would be more

suitable based on clinical judgement.

Rate control-guidelines

• Offer either a standard beta-blocker

• Or a rate-limiting calcium-channel blocker as initial

monotherapy to people with atrial fibrillation who

need drug treatment as part of a rate control

strategy.

• Base the choice of drug on the person's

symptoms, heart rate, comorbidities and

preferences when considering drug treatment.

Rate control

• Consider digoxin monotherapy for people with

non-paroxysmal atrial fibrillation only if they are

sedentary

• If monotherapy does not control symptoms, and if

continuing symptoms are thought to be due to

poor ventricular rate control, consider combination

therapy with any 2 of the following:

– Beta-blocker

– Digoxin

– Diltiazem

– Do not offer amiodarone for long-term rate control

Rhythm control

• Consider pharmacological and/or electrical rhythm

control for people with atrial fibrillation whose

symptoms continue after heart rate has been

controlled or for whom a rate-control strategy has

not been successful

Rhythm control

Cardioversion

•For people having cardioversion for atrial fibrillation

that has persisted for longer than 48 hours, offer

electrical (rather than pharmacological)

cardioversion

•Consider amiodarone therapy starting 4 weeks

before and continuing for up to 12 months after

electrical cardioversion to maintain sinus rhythm

Rhythm control

Drug treatment for long-term rhythm control

•If drug treatment for long-term rhythm consider a standard

beta-blocker (that is, a beta-blocker other than sotalol) as

first-line treatment unless there are contraindications

•If beta-blockers are contraindicated or unsuccessful, assess

the suitability of alternative drugs for rhythm control, taking

comorbidities into account

•Dronedarone is recommended as an option for the

maintenance of sinus rhythm after successful cardioversion

in people with paroxysmal or persistent atrial fibrillation

Rhythm control

• Consider amiodarone for people with left

ventricular impairment or heart failure

• Do not offer class 1c antiarrhythmic drugs such as

flecainide or propafenone to people with known

ischaemic or structural heart disease

• Where people have infrequent paroxysms and few

symptoms, or where symptoms are induced by

known precipitants (such as alcohol, caffeine), a

'no drug treatment' strategy or a 'pill-in-the-pocket'

strategy should be considered and discussed with

the person

Amiodarone

• Contains iodine and is related structurally to thyroxine.

• It has complex effects, showing Class I, II, III, and IV actions.

• Its dominant effect is prolongation of the action potential duration and

the refractory period.

• Amiodarone has antianginal as well as antiarrhythmic activity.

Amiodarone

Numerous effects • Blocks the sodium channel (class I action),

• Inhibits sympathetic stimulation (class II action),

• blocks potassium channels (class III action) and

• calcium channels (class IV actions).

• Lengthens the action potential duration and increases the refractory period.

• At the sinus node, it slows the heart rate

• at the atrioventricular node, it slows conduction and predictably reduces the

ventricular response.

Amiodarone

• Therapeutic uses: Amiodarone is effective in the treatment of severe supraventricular and ventricular tachyarrhythmias.

• Despite its side-effect profile, amiodarone is the most commonly employed anti arrhythmic.

Amiodarone pharmacokinetics

• Amiodarone is incompletely absorbed after oral

administration.

• The drug is unusual in having a prolonged half-life of

several weeks, and it distributes extensively in adipose

tissue.

• Full clinical effects may not be achieved until 6 weeks

after initiation of treatment.

Adverse effects-Amiodarone

• Shows a variety of toxic effects. After long-term use, more than half of patients receiving the drug show side effects that are severe enough to prompt its discontinuation.

However, use of low doses reduces toxicity, while retaining clinical efficacy.

Some of the more common effects include

• Interstitial pulmonary fibrosis.

• Gastrointestinal tract intolerance.

• Tremor, ataxia, dizziness.

• hyper- or hypothyroidism.

• Liver toxicity.

• Photosensitivity.

• Neuropathy, muscle weakness.

• Blue skin discoloration caused by iodine accumulation in the skin.

Non drug treatment options

• Ablation (pulmonary

vein)

• Ablate and pace (AV

node ablation)

• Atrial defibrillators

• Maze procedure

• Removal of Left Atrial

Appendage

Antithrombotic Therapy

Antithrombotic therapy

• Do not offer stroke prevention therapy to people

aged under 65 years with atrial fibrillation and no

risk factors other than their sex (that is, very low

risk of stroke equating to a CHA2DS2-VASc score

of 0 for men or 1 for women).

Anticoagulant therapy

Anticoagulation

• Anticoagulation may be with apixaban, dabigatran

etexilate, rivaroxaban or a vitamin K antagonist.

• Consider anticoagulation for men with a CHA2DS2-VASc

score of 1. Take the bleeding risk into account.

• Offer anticoagulation to people with a CHA2DS2-VASc

score of 2 or above, taking bleeding risk into account.

• Discuss the options for anticoagulation with the person

and base the choice on their clinical features and

preferences.

Results

Score of 0 =mild risk of stroke –observe

Score of 1= moderate risk of stroke-consider Aspirin

Score over 1= severe risk of stroke Warfarin

CHA2DS2-VASc

• Congestive heart

failure

• Hypertension

• Age ≥75

• Diabetes

• Stroke

• Vascular disease

• Age 65-74

• Sex category (female)

• Moving away from high, moderate, low risk categories

• Focus on major and clinically relevant non major risk factors

• If score over 1 give warfarin or new agent

• If score of 0-considered truly low risk and no antithrombotic agent required

HAS BLED

• Hypertension

• Abnormal renal/liver function

• Stroke

• Bleeding history or predisposition

• Labile INR

• Elderly (eg age over 65, frailty)

• Drugs/alcohol concomitantly

• Score ≥3 = caution and regular review, correct reversible risk factors if

possible

Oral anticoagulants -Warfarin

• Well established

• Variable dosing

• Requires blood tests

• Unpopular with patients

• Antidote available

• Monitoring means patient compliance is higher

than with most medication

• Needs thorough patient counselling

• Many interactions

How to initiate Warfarin

• This differs depending on indication

• Can be used in Pulmonary Embolism (PE), Deep

Vein Thrombosis (DVT), AF, mechanical heart

valves, etc.

• Need to rule out any contraindication e.g. active

bleeding

• A baseline International Normalised Ratio (INR) is

taken

How to initiate warfarin

• INR definition: index of blood coagulability (normal

INR = 1); anticoagulant therapy (e.g. warfarin)

adjusts INR to 2-4 (i.e. anti-coagulated blood

takes twice to four times as long to clot)

• Target INR for AF,DVT and PE is between 2-3

• Target INR for mechanic heart valve is 2.5-3.5

• Each Trust will have a different protocol for

initiation of warfarin

How to initiate warfarin

• Most patients will be started on 5mg warfarin a

day

• This may be reduced further in elderly and

significant liver disease

• In patients with DVT and PE, they will be given

concomitant Low Molecular Weight Heparin

(LMWH) with warfarin until the INR is within range

this is to ensure they have adequate cover

• In patients with AF this is not required as it is not

as critical to ensure patient is immediately anti-

coagulated.

Oral anticoagulants

The oral anticoagulants available in the UK are

• warfarin

• acenocoumarol

• phenindione

• dabigatran etexilate

• rivaroxaban

• apixaban

Oral anticoagulants

• Dabigatran etexilate, rivaroxaban and apixaban

are relatively newer oral anticoagulants.

Dabigatran etexilate is a direct thrombin inhibitor,

whilst rivaroxaban and apixaban inhibit activated

factor Xa.

• Dabigatran etexilate, rivaroxaban and apixaban

do not require monitoring of the INR.

Dabigatran etexilate, rivaroxaban and

apixaban

• Prophylaxis of venous thromboembolism:

Dabigatran etexilate, rivaroxaban and apixaban

are licensed for use in adults after total hip

replacement or total knee replacement surgery.

Atrial fibrillation:Dabigatran etexilate,

rivaroxaban and apixaban

• Are now recommended as alternatives to warfarin, in the prevention of

stroke and systemic embolism in patients with atrial fibrillation.

• They are as effective as warfarin in the reduction of the relative risk of

stroke and systemic embolisation in patients with atrial fibrillation.

• Their use is limited to non-valvular atrial fibrillation with one or more of

the following risk factors:

For dabigatran etexilate:

– Previous stroke.

– Previous transient ischaemic attack.

– Previous systemic embolism.

– Left ventricular ejection fraction below 40%.

– Symptomatic heart failure of New York Heart Association

(NYHA) class 2 or above.

– Age 75 years or older.

– Age 65 years or older with one of the following: diabetes

mellitus, coronary artery disease or hypertension.

For rivaroxaban and apixaban:

– Congestive heart failure.

– Hypertension.

– Age 75 years or older.

– Diabetes mellitus.

– Prior stroke or transient ischaemic attack.

Dabigatran etexilate, rivaroxaban and

apixaban

• The decision about whether to start treatment with

dabigatran etexilate, rivaroxaban or apixaban

should follow a discussion between the clinician

and patient regarding the risks and benefits

compared with warfarin.

Dabigatran etexilate, rivaroxaban and

apixaban

• The National Institute for Health and Care

Excellence (NICE) recommends two dose options

for dabigatran etexilate - a regular dose and a

lower dose for those patients at high risk of

bleeding.

Dabigatran etexilate, rivaroxaban and

apixaban

• Dabigatran etexilate, rivaroxaban and apixaban

have all been associated with lower rates of

intracranial haemorrhage but also a possible

increase in gastrointestinal bleeding.

Unfractionated Heparin (UFH)

• ‘Conventional heparin’

• Large mucopolysaccharide molecules

• Has immediate anticoagulant properties

• Prevents the production of fibrin from fibrinogen

• Also has effects on the inhibition of production of

activated clotting factors

• Given IV or subcutaneously

• Haemorrhage major adverse effect

• Safer in renal impairment due to shorter half life

than LMWH

Low Molecular Weight Heparins (LMWH)

• Contain smaller polysaccharide chains

• Exhibit anticoagulant effect by inactivating factor

Xa and inactivate platelet bound factor Xa

• E.g. dalteparin, enoxaparin and tinzaparin

• Longer and more predictable half life than UFH

• Predominantly renally excreted therefore care in

renal impairment

• Less likely to cause thrombocytopenia (low

platelets) than UFH

• Can cause Heparin induced thrombocytopenia

(HIT)

Fondaparinux

• Is a synthetic pentasaccharide that binds to

antithrombin III and inhibits factor Xa

• Monitoring not necessary normally as does not

affect coagulation tests

• Can be used in prophylaxis of Venous

thromboembolism (VTE) and treatment of DVT

and PE

• Used in acute management of MI

Questions

References

• Nice Guidance CG 180 : Atrial fibrillation: the

management of atrial fibrillation

• Primary and secondary prevention with new oral

anticoagulant drugs for stroke prevention in atrial

fibrillation: indirect comparison analysis. BMJ

2012; 345

Arrhythmias and Anticoagulation

Faiza Khan and Zahraa Jalal