Download - 2. Arrhythmias
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
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