Atrial Fibrillation Steve McGlynn Specialist Principal Pharmacist (Cardiology), Greater Glasgow and Clyde Honorary Clinical Lecture, University of Strathclyde

Some types of arrhythmia Supraventricular Sinus Nodal Sinus bradycardia Sinus tachycardia Sinus arrhythmia Atrial Atrial tachycardia Atrial flutter Atrial fibrillation AV Nodal AVNSVT Heart blocks Junctional Ventricular Escape rhythms Ventricular tachycardia Ventricular fibrillation

Atrial fibrillation A heart rhythm disorder (arrhythmia). It usually involves a rapid heart rate, in which the upper heart chambers (atria) are stimulated to contract in a very disorganized and abnormal manner. A type of supraventricular tachyarrhythmia The most common arrhythmia

Aetiology Rheumatic heart disease Coronary heart disease (MI) Hypertension Myopericarditis Hypertrophic cardiomyopathy Cardiac surgery Thyrotoxicosis Infection Alcohol abuse Pulmonary embolism Caffeine Exercise Lone AF

Incidence / Prevalence 1.7 / 1000 patients / year 3 / 1000 patients / year (>60 years) 0.4 - 1% (overall) 2 – 4% (>60 years) >8% (>80 years)

Classification New / Recent onset Paroxysmal Persistent Permanent < 48 hours Paroxysmal variable duration self terminating Persistent Non-self terminating Cardiovertable Permanent Non-cardiovertable

Symptoms / Signs Breathlessness / dyspnoea Palpitations Syncope / dizziness Chest discomfort Stroke / TIA 6 x risk of CVA 2 x risk of death 18 x risk of CVA if rheumatic heart disease Irregularly irregular pulse Atrial rate 300-600bpm Ventricular rate depends on degree of AV block 120-160bpm Peripheral rate slower (pulse deficit)

Investigations Electrocardiogram (ECG) All patients May need ambulatory monitoring Transthoracic echocardiogram (TTE) Establish baseline Identify structural heart disease Risk stratification for anti-thrombotic therapy Transoesophogeal echocardiography (TOE) Further valve assessment If TTE inconclusive / difficult

Normal Sinus Rhythm

‘Fast’ AF

‘Slow’ AF

Atrial Flutter

Investigations Electrocardiogram (ECG) All patients May need ambulatory monitoring Transthoracic echocardiogram (TTE) Baseline Structural heart disease Risk stratification for anti-thrombotic therapy Transoesophogeal echocardiography (TOE) Further valve assessment TTE inconclusive / difficult

Diagnosis Based on: ECG Presentation Response to treatment

Treatment objectives Rhythm / rate control Stroke prevention

Treatment strategies New / Recent onset Cardioversion Rhythm control Paroxysmal Rate control or cardioversion during paroxysm Rhythm control if needed Persistent Cardioversion Rhythm control Peri-cardioversion thromboprophylaxis Permanent Rate control Thromboprophylaxis

Pharmacological Options Class Ic Anti-arrhythmics Flecainide / Propafenone Rhythm control May also be pro-arrhythmic Class II Anti-arrhythmics Beta-blockers Mainly rate control Control rate during exercise and at rest Generally first choice Choice depends on co-morbidities The standard classification of antiarrhythmic drugs is Vaughn-Williams. This is based on the effect of the drugs on the action potential. Digoxin is not included. All classes have a place in the management of AF. Choice depends of type of AF, co-morbidities and other patient factors. The Class Ic antiarrhythmics are used to restore and maintain sinus rhythm. They are, however, negatively inotropic (shouldn’t be used in heart failure) and are also pro-arrhythmic, especially if the patient has coronary heart disease. The Class II anti-arrhythmic drugs are the beta-blockers. Mainly used for rate control, and are effective both at rest and during periods of high sympathetic tone e.g. exercise, stress. They are usually first choice unless contra-indicated, e.g. asthma, acute heart failure.

Class III Anti-arryhthmics Amiodarone / Dronedarone Mainly rhythm control May be pro-arrhythmic Concerns over toxicity Class IV Anti-arryhthmics Calcium channel blockers (verapamil / diltiazem only) Rate control only Alternative to beta-blockers if no heart failure Digoxin Does not control rate during exercise Third choice unless others contra-indicated The class III agents are amiodarone and dronedarone, although sotalol, a beta-blocker also has class III effects. They work by prolonging the action potential and therefore both restore and maintain sinus rhythm. Amiodarone is particularly effective but its long term use is limited by serious side effects. Dronedarone is a newer, less toxic but less effective alternative. It’s use is limited in patients with heart failure and there are now concerns about hepatotoxicity. Intravenous amiodarone is useful to restore sinus rhythm in acute AF. The Class IV antiarrhythmics are the calcium channel blockers verapamil and diltiazem. They are useful alternatives to beta-blockers but are contra-indicated in acute and chronic heart failure. Digoxin has been used for hundreds of years. It is of little use in patients who are active since high sympathetic tone overcomes its effect at the AV node. Its main role is in rapid rate control in patients who also present in acute heart failure and in those patients who require long-term management but lead sedentary lifestyles. Plasma levels need to be checked due to a narrow therapeutic index.

Acute AF Treatment will depend on: History of AF Time to presentation (<> 24 hours) Co-morbidities (CHD, CHF/LVSD etc) Likelihood of success (History)

Rhythm control not feasible or safe Rate Vs. Rhythm control Rhythm control not feasible or safe Beta-blocker Verapamil Digoxin (CHF) Rhythm control if possible and safe DC cardioversion (if possible) Amiodarone (CHD or CHF/LVSD) Flecainide (Paroxysmal AF)

Paroxymal AF Rhythm control* Beta-blocker Class 1c agent or sotalol If CHD - sotalol If LVD: Amiodarone Dronedarone? *May be “Pill in the pocket” Antithrombotic therapy as per risk assessment Aspirin 75-300mg warfarin to INR 2-3 See later

Persistent AF Rhythm control Beta blocker No structural heart disease: Class 1c* or sotalol Structural heart disease: amiodarone Rate control As for permanent AF * not if CHD present Antithrombotic therapy as per risk assessment Pre-cardioversion thromboprophylaxis of at least 3 weeks If rate control, as for permanent AF

Permanent AF Beta blocker or Calcium channel blocker and/or Digoxin Amiodarone? Antithrombotic therapy as per risk assessment Aspirin 75-300mg Warfarin to INR 2-3 See later

Stroke prevention (non-rheumatic AF)

Stroke Risk Assessment (CHADS2) C Chronic Heart Failure (1 point) H Hypertension (1 point) A Age > 75 years (1 point) D Diabetes (1 point) S Stroke, TIA or systemic embolisation (2 points) Score < 2: low risk, aspirin or anticoagulant Score ≥ 2: high risk, anticoagulant indicated The choice of anticoagulation versus antiplatelet therapy to reduce the risk of stroke is based on the balance between the stroke risk versus the risk of a serious bleed. The CHADS2 scoring system is commonly used to assess stroke risk. High risk patients should be offered anticoagulation unless contra-indicated. This scoring system has been criticised because it underestimates the effect of age as well as several other factors.

Stroke Risk Assessment (CHA2DS2VASc) Alternative to CHADS2 C Chronic Heart Failure (1 point) H Hypertension (1 point) A Age > 75 years (2 points) D Diabetes (1 point) S Stroke, TIA or systemic embolisation (2 points) V vascular disease (1 point) A Age 65-74 years (1 point) Sc Sex category (1 point if female) THE CHADSVASc scoring system has been proposed as an alternative. It adds in the effect of co-existing vascular disease and being female. It also increases the score factor associated with age. Under this system, more patients are eligible for anticoagulation.

Bleeding Risk Assessment (HAS-BLED) 1 point each for: Hypertension Abnormal renal/liver function (1 for each) Stroke Bleeding history or predisposition Labile INR Elderly (age over 65) Drugs*/alcohol** concomitantly (1 for each) *Drugs that increase bleeding, e.g. aspirin ** Alcohol excess To assess the risk of a bleed on anticoagulation, a scoring system for bleeding has been developed. The HAS-BLED score gives an indication of how high risk a patient is. A score of >3 is considered high risk. No definitive cut-off for avoiding anticoagulation has been defined however. It should be noted that 3 of the criteria also appear in CHADSVASc!

Anticoagulants Warfarin remains standard anticoagulant at present 3 new oral anticoagulants (unlicensed for AF as of June 2011) Dabigatran (Direct thrombin inhibitor) Rivaroxiban (Factor Xa inhibitor) Apixaban (Factor Xa inhibitor) Fixed doses No monitoring At least as effective as warfarin Safer than warfarin? Much more expensive (even allowing for INR costs) Place in therapy not clear yet Warfarin is currently the anticoagulant of choice. This is based on the experience gained over decades of use. It does however have its limitations, mainly dose variability. Three new oral anticoagulants have been developed. All have been shown to be either: More effective than warfarin (high dose dabigatran) Non-inferior to warfarin (low dose dabigatran, rivaroxaban, apixaban) As safe as warfarin (high dose dabigatran) Safer than warfarin (low dose dabigatran) As of July 2011 none are licensed for AF stroke prevention. Dabigatran is likely to be approved soon and is due to be reviewed by SMC late summer 2011. These drugs are fixed dose and do not require INR monitoring. Despite these advantages there are concerns around adherence (no monitoring, BD dosing) and safety (they are not easily reversed unlike warfarin). They are also considerably more expensive, even allowing for no monitoring. There place has yet to be established in NHS Scotland although guidance is expected late summer/early autumn.

Conclusions AF is a common condition. Patients may be unaware of its presence and are therefore at risk of a stroke Alternative treatment strategies exist to control symptoms Alternative treatment strategies exist to reduce the risk of stroke Patient education and choice are central to improving the likelihood of treatment success