Atrial Fibrillation Cardiovascular ISCEE 26th October 2010

How might AF present in GP? People with an irregular pulse +/- Breathlessness Palpitations Chest discomfort Syncope/dizziness Reduced exercise tolerance, malaise or polyuria A potential complication of AF such as stroke, TIA or heart failure Symptoms - Many people with AF have no symptoms, and the irregular pulse is detected incidentally. In two studies with 410 participants, breathlessness, chest pain, and palpitations were found to be the most common presenting symptoms in emergency admissions with newly diagnosed or previously diagnosed AF. In one study with 756 participants, breathlessness was the most commonly reported symptom in chronic and recent onset AF (47%) and palpitations was the most commonly reported symptom in paroxysmal AF (79%). Reduced exercise tolerance and malaise may occur due to a rapid heart rate or to a complication, such as heart failure [MeReC, 2002; Snow et al, 2003]. Polyuria may occur owing to the release of atrial natriuretic peptide during episodes of AF [Fuster et al, 2006a].

Absence of an abnormal pulse makes a diagnosis of AF unlikely But its presence does not reliably indicate AF. Suspect paroxysmal AF if symptoms are episodic and last less than 48 hours. Irregular pulse - In one UK study of 916 people older than 65 years of age, an irregular pulse was found to be sensitive (93–100%) to the presence of AF. The negative predictive values ranged from 99–100% depending on age. In other words, AF can be confidently excluded if the person does not have an irregular pulse. Paroxysmal AF - episodes that last longer than 30 seconds but less than 7 days (often less than 48 hours) and are self-terminating and recurrent.

What do we need to do with them? ECG to confirm diagnosis If paroxysmal AF suspected and 12-lead ECG is normal then arrange ambulatory electrocardiography Bloods CXR ECG – If AF is present, the ECG will show no P-waves, a chaotic baseline, and an irregular ventricular rate. The ventricular rate is often 160–180 beats per minute, but can be lower. A lower rate is frequently found in people who are asymptomatic. The ventricular complexes look normal unless there is a ventricular conduction defect. See a typical tracing in the next slide. Ambulatory ECG recording - A 24-hour ambulatory ECG monitor is normally used in people with suspected asymptomatic episodes of paroxysmal AF (incidental finding of an intermittent irregular pulse) or symptomatic episodes that are less than 24 hours apart. An event recorder ECG is normally used in people who have symptomatic episodes more than 24 hours apart. In some centres, a 7-day Holter monitor is used as an alternative to an event recorder, especially when asymptomatic paroxysms of AF are suspected.

TFTs – exclude hyperthyroidism FBC – exclude anaemia U&Es, Bone Profile, Glucose – exclude electrolyte disturbances which may precipitate AF LFTs and clotting screen – assess suitability for warfarin CXR – exclude lung abnormality such as lung cancer, also to detect heart failure An electrocardiogram should already have been done to confirm the diagnosis of atrial fibrillation. An electrocardiogram may also indicate a possible underlying cause (such as an old myocardial infarction, left ventricular hypertrophy, or a pre-excitation syndrome). Thyroid function tests (to exclude hyperthyroidism). Full blood count (to exclude anaemia). Blood urea and electrolytes, calcium, and glucose measurement (to exclude electrolyte disturbances, which may precipitate atrial fibrillation). Liver function tests and clotting screen (to assess suitability for warfarin). Chest radiography (to assess a suspected lung abnormality, such as lung cancer; this test may also help to detect heart failure).

Which ones need to be referred? Urgently Patients with: Pulse > 150 bpm and/or low BP (systolic less than 90 mmHg) Loss of consciousness, severe dizziness, ongoing chest pain or increasing breathlessness A complication of AF – stroke, TIA, acute HF Admit (or refer) for urgent assessment and intervention if the person has any of the following: A rapid pulse (greater than 150 beats per minute) and/or low blood pressure (systolic blood pressure less than 90 mmHg). Loss of consciousness, severe dizziness, ongoing chest pain, or increasing breathlessness. A complication of atrial fibrillation (AF), such as stroke, transient ischaemic attack, or acute heart failure.

Which ones need to be referred? Outpatients New onset AF + Young patient (age less than 50 yrs) Suspected paroxysmal AF Concurrent valve disease LV systolic dysfunction on echo Wolff-Parkinson-White syndrome or a prolonged QT interval is suspected on the ECG Heart rate is difficult to control Person continues to have symptoms despite rate control treatment Refer people with new-onset AF to a specialist in cardiology if: The person is young (for example less than 50 years of age); Paroxysmal AF is suspected; Rhythm control is the preferred treatment, or there is uncertainty regarding this (see Rate or rhythm control); Drug treatment for rate control or antithrombotic treatment that can be used in primary care are contraindicated; The person is found to have valve disease or left ventricular systolic dysfunction on echocardiography; Wolff–Parkinson–White syndrome or a prolonged QT interval is suspected on the electrocardiogram; Heart rate is difficult to control, or the person continues to have symptoms despite rate-control treatment (see Management after starting rate-control treatment).

Rhythm vs Rate Rhythm control preferred treatment for paroxysmal AF and in people with persistent AF with any of the following: Symptomatic < 65 yrs of age First presentation with lone AF AF secondary to a treated or corrected precipitant (eg infection) Congestive heart failure Rate controlled preferred treatment for permanent AF and in people with persistent AF and any of the following: > 65 yrs age Coronary artery disease Contraindications to antiarrhythmic drugs Unsuitable for cardioversion Clarification / Additional information Rate control involves the use of drugs to slow the ventricular heart rate, in an attempt to minimize symptoms and associated morbidity of atrial fibrillation (AF). Rate control will not stop the atria from fibrillating. Rhythm control involves the use of drugs to maintain normal sinus rhythm once AF has terminated (spontaneously or after electrical or pharmacological cardioversion). Rhythm control is often needed long term to help prevent recurrence of AF. Cardioversion is unsuitable for people with: Contraindications to anticoagulation; Structural heart disease (for example a large left atrium greater than 5.5 cm or mitral stenosis) that makes it unlikely that sinus rhythm would be maintained following successful cardioversion; A long duration of AF (usually greater than 12 months); A history of multiple failed attempts at cardioversion and/or relapses, even with concomitant use of antiarrhythmic drugs or non-pharmacological approaches; An ongoing but reversible cause of AF, until the precipitant has been effectively treated (such as thyrotoxicosis). Basis for recommendation - These recommendations are based on the NICE guideline ‘Atrial fibrillation: national clinical guideline for management in primary and secondary care’ [National Collaborating Centre for Chronic Conditions, 2006]. After reviewing the evidence (five randomized controlled trials and one meta-analysis) comparing rate control with rhythm control on different outcomes, NICE concluded that overall there is no difference between rhythm control and rate control in terms of mortality or quality of life. NICE states that rate control is the preferred treatment in people with permanent AF (as by definition rhythm control has been tried and failed, or is not an option), and in people with persistent AF who are older than 65 years of age, have evidence of coronary heart disease, or have no evidence of heart failure, as there is some evidence that rate control may be superior in these groups. In one study, there was a significant difference in favour of rate control in terms of all-cause mortality in people older than 65 years of age and in people with coronary artery disease.In three studies, rhythm control compared with rate control resulted in a higher rate of adverse effects and hospital admissions and a higher incidence of arrhythmias in people with recurrent AF. In one study, rhythm control was associated with a lower incidence of all-cause mortality in people with heart failure. However, CKS found a subsequent prospective, open-labelled trial (n = 1376) with 2 years of follow-up which suggests that in people with AF and symptoms of heart failure, rhythm control and rate control may result in similar cardiovascular outcomes [Roy et al, 2008].

GP Management Rate control can be started in primary care Beta-blockers, rate-limiting Ca-channel blockers, digoxin) But rhythm control should only be done under specialist supervision Amiodarone, fleicanide, sotalol Start rate-control anyway if the person does not need admission but Resting pulse >/= 90 bpm Heart rate is fast on exertion, resulting in limited exercise tolerance Clarification / Additional information Heart rate control: NICE recommends that resting heart rate should be controlled to less than 90 beats per minute, and that heart rate on exercise should be controlled to less than 110 beats per minute in people who are inactive or 200 beats per minute minus their age in active people [NICE, 2006]. A consensus statement from the Royal College of Physicians of Edinburgh suggests a target resting heart rate of less than 90 beats per minute and less than 180 beats per minute during exercise [RCGP, 1999]. An international guideline states that criteria for rate control vary with age and suggests that ventricular rate should be controlled between 60–80 beats per minute at rest and between 90–115 beats per minute during moderate exercise [Fuster et al, 2006b]. In clinical practice, the target heart rate during exercise may need to be adjusted depending on the level of exercise the person can manage. For example, a rate of 170 beats per minute is inadequate rate control if the person has only walked up the corridor. Basis for recommendation These recommendations are based on the NICE guideline ‘Atrial fibrillation: national clinical guideline for management in primary and secondary care’ [National Collaborating Centre for Chronic Conditions, 2006]. The aim of rate control is to minimize symptoms associated with excessive heart rate (such as breathlessness) and prevent tachycardia-associated cardiomyopathy [Fuster et al, 2006b]. Adequate rate control has not been well studied with respect to quality of life, or symptoms or development of cardiomyopathy, and no standard method for assessment of rate control has been established to guide management. CKS has outlined the suggested rate control targets from several guideline groups [RCGP, 1999; Fuster et al, 2006a; National Collaborating Centre for Chronic Conditions, 2006].

Initial Rate Control Treatment Beta-blocker or rate limiting Ca-channel blocker (diltiazem or verapamil) unless this is contraindicated Choice between the 2 groups depends on current medication and co-morbidities Diltiazem preferred to verapamil because verapamil has a greater negative inotropic effect and interacts with digoxin Digoxin suitable for older sedentary people in whom rate control is not needed during exercise Diltiazem (off-licensed use for atrial fibrillation) is preferred to verapamil because verapamil has a greater negative inotropic effect on the heart and interacts with digoxin. Basis for recommendation: These recommendations are based on the NICE guideline ‘Atrial fibrillation: national clinical guideline for management in primary and secondary care’ [National Collaborating Centre for Chronic Conditions, 2006]. After reviewing 12 small randomized or serial crossover trials comparing beta-blockers and calcium-channel blockers for atrial fibrillation (AF), NICE concluded that: Both calcium-channel blockers and beta-blockers are more effective than digoxin in controlling heart rate at high levels of physical exertion, but there is no difference during normal daily activities; There is no significant difference between calcium-channel blockers and beta-blockers in terms of heart rate control; Beta-blockers versus calcium-channel blockers - One crossover study found no difference between diltiazem and atenolol in terms of heart rate over 24 hours or during exercise. A second crossover study found no difference between verapamil and atenolol in heart rate at rest or after exercise. Calcium-channel blockers versus digoxin - Seven studies found no difference in heart rate between verapamil or diltiazem and digoxin, either at rest or during normal daily activity. Seven studies found that verapamil or diltiazem resulted in a lower heart rate during exercise compared with digoxin. Beta-blockers versus digoxin - Three studies found no difference in average heart rate between digoxin and beta-blockers while at rest or during normal daily activity. Atenolol and labetalol controlled heart rate during exercise more effectively than digoxin. One study found that atenolol significantly reduced heart rate compared with digoxin both at rest and after exercise.

Subsequent Management Review within 1 week – is the patient tolerating the drug? Review symptoms, heart rate, BP. If drug not tolerated, prescribe an alternative. If symptoms not controlled, either increase dose or consider combination treatment. To control symptoms during normal activities only, use beta-blocker/Ca-blocker with digoxin. To control symptoms normal activities AND during exercise, use Ca-blocker with digoxin. Within 1 week, check whether the person is tolerating the drug and review symptoms, heart rate, and blood pressure.If the person cannot tolerate the drug, prescribe an alternative (see Initial drug treatment for rate control). If the person's symptoms and/or heart rate are not controlled: If they are not taking the maximum drug dose, consider increasing the dose to control symptoms, or If they are taking the maximum drug dose, consider combining drug treatments. To control symptoms during normal activities only, use a beta-blocker or calcium-channel blocker (diltiazem or verapamil) with digoxin. To control symptoms during normal activities and during exercise, use a calcium-channel blocker (diltiazem or verapamil) with digoxin. If the person is already taking a beta-blocker, it may be more practical to add in digoxin first, and if symptoms are still not controlled, then switch the beta-blocker with a calcium-channel blocker.

Subsequent Management Do not use a beta-blocker and Ca-blocker to control AF in primary care If symptoms are not controlled by beta-blocker plus digoxin OR Ca-blocker plus digoxin refer to cardiology These recommendations are based on the NICE guideline ‘Atrial fibrillation: national clinical guideline for management in primary and secondary care’ [National Collaborating Centre for Chronic Conditions, 2006]. Rate control is not always achieved with a single drug, and combination drug treatment may be required. Beta-blocker with digoxin versus beta-blocker alone - One crossover study with 12 participants found that atenolol used in combination with digoxin resulted in a lower heart rate over 24 hours than that achieved with atenolol alone [Farshi et al, 1999]. This study found no statistically significant difference in heart rate during periods of exercise. Calcium-channel blocker with digoxin versus calcium-channel blocker alone - Four crossover studies (with about 15 participants in each study) found that diltiazem or verapamil used in combination with digoxin was more effective in controlling heart rate over 24 hours, as well as during periods of exercise, than either diltiazem or verapamil alone. Combination of beta-blocker and calcium-channel blocker - NICE does not recommend the use of a beta-blocker and rate-limiting calcium-channel blocker for atrial fibrillation in primary care owing to the increased risk of bradycardia with this combination. Referral- If digoxin with a beta-blocker, or digoxin with a calcium-channel blocker, is ineffective or not tolerated, a specialist may consider the use of amiodarone, or diltiazem with a beta-blocker, to control atrial fibrillation. Alternatively, a non-pharmacological approach (mainly atrioventricular node ablation coupled with pacing) might be considered.

Antithrombotic Treatment Everyone with AF (paroxysmal, persistent, permanent) should be offered antithrombotic treatment to reduce their risk of stroke Offer either aspirin or warfarin without delay after confirming a diagnosis of AF Choice should be based on person’s risk of stroke Assess bleeding risk, likelihood of compliance with treatment and preferred options Low risk of stroke – aspirin Moderate risk of stroke – either aspirin or warfarin High risk of stroke – warfarin These recommendations are based on the NICE guideline ‘Atrial fibrillation: national clinical guideline for management in primary and secondary care’ [National Collaborating Centre for Chronic Conditions, 2006]. Antithrombotic treatment for all people with atrial fibrillation - AF is an independent risk factor of stroke; the annual risk for stroke is five to six times higher in people with AF than in people in sinus rhythm. Strokes that occur in association with AF are more likely to result in greater mortality, morbidity, and disability and longer hospital stays than strokes that occur in people without AF. Good evidence indicates that antithrombotic treatment reduces the risk of stroke in all people with AF. Starting antithrombotic treatment after a diagnosis of AF - Provided that the person has no contraindications to antithrombotic treatment (such as uncontrolled hypertension), NICE states that treatment should be started as soon as possible after a diagnosis of AF to minimize the risk of stroke. Stroke risk stratification can be easily performed in primary care on the basis of clinical criteria; therefore, a primary healthcare professional should not delay antithrombotic treatment by waiting for a cardiology opinion. Antithrombotic treatment compared with placebo or no treatment - After reviewing the evidence, NICE concluded that treatment with warfarin or an antiplatelet drug is more effective than placebo or no treatment in the prevention of cardioembolic stroke in people with AF. Two systematic reviews found evidence that aspirin was associated with a statistically non-significant reduction in stroke risk. However, a statistically significant risk reduction in a combined outcome of stroke, myocardial infarction, or vascular death was seen. Three systematic reviews found evidence that compared with placebo, warfarin significantly reduced the risk of stroke by two-thirds in people with AF. Compared with placebo, warfarin was associated with an increased risk of extracranial bleeding, but there was no increased incidence of intracranial bleeding.

Assessing Bleeding Risk Factors that increase risk of bleeding Age > 75yrs Use of antiplatelet drugs Use of NSAIDs Polypharmacy Uncontrolled hypertension Hx of bleeding (bleeding peptic ulcer, cerebral haemorrhage) Hx of previous poorly controlled anticoagulation therapy The National Institute for Health and Clinical Excellence does not state that a formal bleeding risk assessment is necessary before starting antithrombotic treatment, but it provides a list of risk factors that increase the risk of bleeding with warfarin. Warfarin versus aspirin - Good evidence indicates that warfarin is more effective than aspirin for preventing stroke or vascular events in people with atrial fibrillation but is associated with a higher risk of intracranial and extracranial bleeding. For people without prior stroke or transient ischaemic attack (TIA), a Cochrane systematic review (eight randomized controlled trials [RCTs]) found that warfarin reduced the risk of stroke and other major vascular events in people with AF by about one-third compared with antiplatelets [Aguilar et al, 2007]. For people who have had a stroke or TIA, a Cochrane systematic review (two RCTs) found that warfarin reduced the risk of stroke by a half, and the risk of any vascular event by one-third, compared with antiplatelets [Saxena and Koudstaal, 2004b]. For people 75 years of age or older, an open-label RCT (973 participants) found that warfarin (target international normalized ratio 2.0–3.0) reduced the risk of stroke by half and the risk of vascular events by two-thirds, compared with aspirin 75 mg daily [Mant et al, 2007b]. Clopidogrel alone - NICE do not recommend the use of clopidogrel in AF. Clopidogrel is not licenced for AF and there is no trial evidence to support its use. However, a number of CKS expert reviewers do state that they would use clopidogrel as an alternative treatment option in people with a true aspirin allergy. Combining antithrombotic treatment - NICE states that if warfarin is offered, aspirin should not be taken concomitantly to prevent stroke, as it provides no additional benefit and may increase the risk of bleeding. CKS does not recommend the use of aspirin plus clopidogrel in primary care to reduce the risk of stroke in AF. There is evidence that warfarin significantly reduces the risk of stroke, myocardial infarction, and vascular events compared with clopidogrel plus aspirin [Connolly et al, 2006]. Warfarin did not increase the risk of bleeding compared with clopidogrel plus aspirin. A recently published trial found evidence that combined treatment with clopidogrel plus aspirin reduces the risk of major vascular events compared with aspirin alone [ACTIVE Investigators et al, 2009]. However, this trial also found evidence that combined treatment with clopidogrel plus aspirin was associated with a two-fold increased risk of major bleeding.

Assessing Stroke Risk High risk Moderate risk Low risk Previous ischaemic stroke / TIA or thromboembolic event > 75yrs age with risk factors (hypertension, diabetes, coronary artery disease, peripheral artery disease) Clinical evidence of valve disease or heart failure Impaired LV function on echo Moderate risk > 65yrs age without risk factors < 75yrs age with risk factors Low risk < 65yrs age without risk factors Based on NICE guidelines 2006. On the basis of cohort studies, the Scottish Intercollegiate Guidelines Network published guidance showing the risk of stroke in people with atrial fibrillation (AF) considered to be at low, moderate, and high risk. For more information, see the antithrombotic therapy section in the SIGN guidance [SIGN, 1999]. Risk factors for stroke - A systematic review (search date October 2005, seven studies) suggests that prior stroke or transient ischaemic attack (TIA), advancing age, hypertension, and diabetes are independent risk factors for stroke in people with AF [Stroke Risk in Atrial Fibrillation Working Group, 2007]. Absolute stroke rates were in the range 6–9% per year for prior stroke or TIA, 1.5% to 3% per year for history of hypertension, 1.5–3% per year for age more than 75 years, and 2.0–3.5% per year for diabetes. In the systematic review, evidence for heart failure and coronary artery disease as independent risk factors for stroke is inconclusive. However, NICE includes heart failure and vascular disease as independent risk factors for stroke on the basis that left ventricular dysfunction is associated with an increased risk of stroke. Atherosclerotic vascular disease is also a risk factor for stroke, with a poor prognosis when associated with AF [Goto et al, 2008].

CHADS2 Congestive heart failure = 1 Hypertension (or treated hypertension) = 1 Age older than 75 years = 1 Diabetes mellitus = 1 previous Stroke or TIA = 2 Treat with aspirin if total score is 0 or 1 Use warfarin if score is 2 or more CHADS2 for stroke risk - The CHADS2 score was designed to provide a simple approach to assessing stroke risk in primary care. The score was validated by a study on people 65–95 years of age with nonrheumatic AF who were not prescribed warfarin [Gage et al, 2004].The CHADS2 criteria have been assessed against risk factors refined to form the NICE criteria, and both were found to be similar for predicting event rates in a cohort prospectively followed up for stroke and vascular events [Lip et al, 2006].

References NICE 2006 ‘Atrial Fibrillation’ Clinical Knowledge Summaries: ‘Atrial Fibrillation’