Atrial fibrillation

Caroline Medi, Graeme J Hankey and Saul B Freedman
Med J Aust 2007; 186 (4): 197-202. || doi: 10.5694/j.1326-5377.2007.tb00862.x
Published online: 19 February 2007


Prevention of AF

Use of angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers,5 and statins may reduce the incidence of AF, as may fish oils, which alter atrial membrane composition.4 After cardiac surgery, where postoperative AF occurs in about 25% of patients, pretreatment with β-blockers, sotalol, amiodarone, and statins has been shown to reduce the incidence.4,6,7

Strategic objectives in the management of AF

Objectives in the management of AF are to:

Identification of associated or causative factors

AF is most commonly caused by hypertension, ischaemic heart disease, heart failure, valvular heart disease, and thyrotoxicosis, but other treatable causes exist (Box 1). The minimal clinical evaluation comprises a history, physical examination, electrocardiography, transthoracic echocardiography, and blood tests of thyroid, renal and hepatic function. Additional tests may be required to exclude other conditions according to clinical suspicion.

Rate or rhythm strategy

Most patients with AF require control of the heart rate for symptomatic relief, and to prevent tachycardia-induced cardiomyopathy. Digoxin is no longer the drug of first choice for rate control (I/C; see Box 2 for key to evidence levels);4 β-blockers are the most effective agents for monotherapy, followed by verapamil and diltiazem,8 as these drugs control both exertional and resting heart rate (I/B).

The decision to attempt cardioversion and maintain sinus rhythm, rather than just control heart rate, depends on the long-term frequency and hazards of AF, and risks of cardioversion and antiarrhythmic therapy. Older patients (> 65 years) with recurrent persistent AF at high risk of stroke (CHADS2 score ≥ 1, see “Stroke risk stratification” below) have similar outcomes (stroke or mortality) with either rate or rhythm control, and a trend towards fewer hospitalisations for those managed with rate control.9 Rate control is more suitable for older patients with asymptomatic persistent or permanent AF, whereas young patients with highly symptomatic paroxysmal AF may require rhythm control.

Sinus rhythm probably does confer a benefit, particularly for patients with heart failure. However, because drugs are relatively ineffective at long-term maintenance of sinus rhythm (60% in sinus rhythm at 1 year on amiodarone and 40% with sotalol),9 and have significant cardiac and extra-cardiac toxicities, including ventricular tachycardia and pulmonary fibrosis, this benefit is negated. A rhythm control strategy is therefore associated with frequent AF recurrences, which may be asymptomatic, and places the patient at risk of stroke unless continuously treated with effective antithrombotic prophylaxis.

Catheter ablation for AF

This procedure involves application of radiofrequency ablation to electrically isolate the pulmonary veins, with or without other lesions to attempt cure of AF. Success rates are variable, but approximate 75%, although this may require multiple procedures.10 If AF recurs, episodes may be less symptomatic or asymptomatic. Catheter ablation is associated with a 3%–6% risk of major complications, including pulmonary vein stenosis, thromboembolism, and the rare (0.6%) but often fatal atrio-oesophageal fistula. It is safest and most successful in patients younger than 70 years with paroxysmal AF for whom anti-arrhythmic therapy has been ineffective and who have a left atrial diameter < 5 cm and left ventricular ejection fraction > 40%. Greater understanding of the mechanisms underlying AF may increase the efficacy of this procedure, but currently ablation is not applicable to the large numbers of elderly patients who develop this arrhythmia.

Prevention of thromboembolism

AF predisposes to the formation of blood clots within the left atrium (LA) and particularly the left atrial appendage (LAA) (Box 3), and these may embolise to the systemic circulation. Consequently, AF is an independent risk factor for cardioembolic ischaemic stroke. Although most strokes in people with AF are embolic from the LA/LAA, about a quarter may originate elsewhere — from the left ventricle, heart valves, and extracranial and intracranial arteries. Cardioembolic strokes in patients with AF are typically larger, associated with higher early mortality, and occur in older patients compared with strokes in patients with sinus rhythm (Box 4).

Optimal thromboprophylaxis for patients with AF is individualised and requires an assessment of:

There is considerable evidence from trials to guide estimates of the risk of stroke, and the potential benefits of either anticoagulant or antiplatelet therapy, but the risk of major haemorrhage is much more difficult to assess, with less evidence to inform decisions, which therefore remain subjective. The patient must be an active partner in the decision on whether to take an anticoagulant for life. This takes some time to explain, as the patient must have a clear understanding of both potential risks and benefits.

Risk of stroke

Among patients with non-valvular AF, the risk of ischaemic stroke averages 5% per year (range, 3%–8%), about 3–5 times that of people in sinus rhythm.11 However, the risk is greatly influenced by individual patient characteristics (Box 5). For patients with lone AF (younger than 60 years with no clinical history or echocardiographic signs of cardiopulmonary disease), the cumulative risk of stroke over 15 years is very low (about 1.3%).12 For patients with non-valvular AF, the strongest independent predictor of stroke is prior stroke or transient ischaemic attack (TIA) (relative risk [RR], 1.9–3.7), which increases the annual risk of subsequent stroke to about 12% per year with no antithrombotic therapy, and about 10% per year with aspirin.13 Increasing age increases the annual risk of stroke from 1.5% in ages 50–59 years to 23% in those aged 80–89 years.11 Other independent risk factors for ischaemic stroke are heart failure with systolic dysfunction, hypertension, and diabetes mellitus (Box 5).14

Antithrombotic therapy
Non-valvular AF
Warfarin or aspirin

Adjusted-dose warfarin reduces the relative risk of stroke by 62%,18 with absolute risk reductions of 2.7% per year for primary prevention and 8.4% per year for secondary prevention. Major extracranial bleeding is increased by warfarin therapy (absolute risk increase, 0.3% per year).18 Aspirin is less efficacious, with only 22% relative risk reduction, and absolute risk reductions of 1.5% and 2.5% per year for primary and secondary prevention, respectively.19 Aspirin appears to prevent non-disabling non-cardioembolic ischaemic strokes more than disabling cardioembolic strokes.19 Treating 1000 patients with AF for 1 year with oral anticoagulant rather than aspirin would prevent 23 ischaemic strokes while causing 9 additional major bleeds.

Warfarin versus clopidogrel plus aspirin

Warfarin (INR, 2–3) is superior to clopidogrel 75 mg plus aspirin 75–100 mg for prevention of vascular events in patients with AF at high risk of stroke (CHADS2 score ≥ 1), reducing the annual risk of stroke from 5.6% with dual antiplatelet therapy to 3.9% with warfarin (RR, 0.69; 95% CI, 0.57–0.85).20 However, these results apply primarily to patients previously exposed to warfarin therapy. For patients new to both treatments, post hoc analysis found the benefits of warfarin were not well defined. In routine practice, the superiority of warfarin could be negated by poor INR control, whereas the major bleeding rate associated with clopidogrel plus aspirin may approximate that of warfarin.

Treatment gap

Newly diagnosed or prior AF occurs in 15%–38% of patients presenting with ischaemic stroke, and increases mortality and disability (Professor G Donnan, NEMESIS study, personal communication).25 Therapeutic anticoagulation reduces the risk of disabling stroke; however, only about 10%–20% of patients with known AF are adequately anticoagulated immediately before their stroke.26,27 In a recent study, a third of patients with AF were on no treatment at the time of stroke, a third were on antiplatelet treatment, and a quarter were on warfarin with subtherapeutic INR; only one-eighth were on adequate warfarin at the time of the stroke.26

The reasons for undertreatment with antithrombotic agents are complex, but include a lack of knowledge about trials and guidelines,27 perceived “potential contraindications”, and fear of bleeding. Warfarin use increases in patients reviewed by cardiologists and by younger GPs.27

Elderly patients with AF

Elderly patients with AF have a greater net benefit from anticoagulation, at the expense of an increased risk of major haemorrhage.28,29 Cognitive function, falls risk, compliance, access to INR testing facilities, drug interactions due to polypharmacy, and the required changes in diet and lifestyle must be taken into account before committing an elderly patient to indefinite anticoagulation.

Warfarin use is very unlikely in patients older than 85 years, despite evidence of its safety in selected patients.30 Aiming for an INR of 2 may be a reasonable benefit–risk trade-off for primary prevention in elderly patients with non-valvular AF,4 although usual practice is to give aspirin in the very elderly.

When dual antiplatelet therapy and warfarin are both required

Patients on warfarin for AF may require additional antiplatelet therapy, such as after angioplasty. There is little evidence to guide management of anticoagulation and antiplatelet therapy in this context, and there is considerable variability in the approach taken by cardiologists.31 A balance is needed between preventing stent thrombosis and stroke, and minimising bleeding risk. In the absence of warfarin, dual antiplatelet therapy is required for longer with drug-eluting than bare metal stents (1 year, compared with about 4 weeks).32,33 When the presentation is an acute coronary syndrome, clopidogrel is beneficial for up to 1 year. Patients with a CHADS2 score ≤ 1 may have adequate protection against stroke during this time with antiplatelet drugs, and warfarin may be resumed thereafter. Patients with a CHADS2 score ≥ 2 or valvular AF may require a limited period with triple therapy until one or both antiplatelet drugs can be safely ceased (IIb/C).

  • Caroline Medi1
  • Graeme J Hankey2,3
  • Saul B Freedman1

  • 1 Department of Cardiology, Concord Repatriation General Hospital, University of Sydney, Sydney, NSW.
  • 2 Stroke Unit, Royal Perth Hospital, Perth, WA.
  • 3 School of Medicine and Pharmacology, University of Western Australia, Perth, WA.



We gratefully acknowledge the assistance of Dr Andy Yong for providing the transoesophageal echo image of a left atrial appendage thrombus.

Competing interests:

Saul Freedman received an honorarium for being on the AstraZeneca international advisory board for ximelagatran, a drug which has been removed from the market for liver toxicity as mentioned in the article. Graeme Hankey is a member of the executive committee of the rivaroxaban in atrial fibrillation trial (Johnson & Johnson Pharmaceutical Research and Development, USA), the steering committee of the atrial fibrillation trial of monitored, adjusted dose vitamin K antagonist, comparing efficacy and safety with unadjusted SanOrg 34006/idraparinux (AMADEUS) trial (Sanofi Aventis), and the stroke advisory committee of atrial fibrillation clopidogrel trial with irbesartan for prevention of vascular events (ACTIVE) trial (Sanofi Aventis). He was a member of international and national advisory boards for ximelagatran (AstraZeneca), for which he received honoraria and travel expenses to attend meetings.

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