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At the heart of general practice since 1960

The treatment - atrial fibrillation

Dr Dominic Kelly, consultant cardiologist, discusses how to treat atrial fibrillation

Treatment of atrial fibrillation is based on two aims. First and most importantly is prevention of thromboembolic disease, predominantly the reduction of embolic stroke.4 Secondly, if patients describe symptoms that can be attributed to the AF, these should be appropriately controlled. In addition, AF is often associated with other diagnoses that also require management such as hypertension, heart failure and thyroid disease, among others.

Several terms have been applied to AF. The most recent European Society of Cardiology (ESC) guidelines1 propose classification in to five patterns of AF. Management of patients with AF is strongly dependant on the pattern at presentation.

AF patternDefinition

First diagnosed

AF not previously identified, irrespective of the duration of the arrhythmia

Paroxysmal

Self terminating and not lasting longer than 7 days (including those cardioverted in this time period)

Persistent

Lasting longer than 7 days, including those terminated by cardioversion

Long standing persistent

Continuously lasting >1 year

Permanent

AF accepted by patient and physician and rhythm control strategies not pursued

Standard current treatment

Anticoagulation

The CHA2DS2-VASc score is a validated risk assessment tool which is comprised of six patient features, as shown below.

CHA2DS2-VASc scoreAnnual stroke/thromboembolism risk

0

0

1

1.3

2

2.2

3

3.2

4

4.0

5

6.7

6

9.8

7

9.6

8

12.5

9

15.2

The decision to anticoagulate should take into account the thromboembolic risk for the individual patient (via the CHA2DS2-VASc score). Anticoagulation can prevent the majority of ischaemic strokes in AF and is superior to both no treatment and antiplatelet therapy.2 The net clinical benefit (benefit versus adverse effects) is almost universal, with the exception of those patients at very low stroke risk, and therefore oral anticoagulation should be given to the majority of patients with AF. Despite the weight of evidence in favour of oral anticoagulation, underuse and premature termination of these therapies is common. A perceived ‘high risk’ of bleeding and the efforts required to monitor INR levels in those patients on vitamin K antagonists are the most common reasons to withhold or stop therapy. The reduction in stroke and overall superior net clinical benefit with oral anticoagulation therapy includes those patients often perceived too frail or at risk of falling and therefore head injury.3,4

ESC guidelines suggest oral anticoagulation should be considered in patients with a CHA2DS2-VASc score of 1 for males and 2 for females and are indicated in patients with a CHA2DS2-VASc score of 2 or greater for males or 3 or greater for females.

Several bleeding risk scores have been developed, mainly in patients receiving vitamin K antagonists. Bleeding risk scores often include patient features present in the CHA2DS2-VASc score and so are often increased in those patients that we are considering for anticoagulation. It is important remember that, in large, these scores should not be used to withhold therapy but to identify and treat risk factors to reduce the risk of adverse events. The HAS-BLED score has been advocated to assess the bleeding risk prior to a decision to commence anticoagulation. HAS-BLED is a scoring system developed to assess one year risk of major bleeding. This scoring system allocates one point to each of the following patient factors below. Current ESC guidelines suggest a score of ≥3 indicates high risk and some caution and regular review of the patient to address these risks are needed.

  • - Hypertension
  • A - Abnormal renal and liver function
  • S - Stroke
  • B - Bleeding
  • L - Labile INRs
  • E - Elderly
  • D - Drugs or alcohol

Choice of anticoagulant

Vitamin K antagonists, such as warfarin, have been available for many years. They have the benefit of experience of use and long standing clinical data. The use of vitamin K antagonists is, however, limited by a narrow therapeutic window and the necessity to monitor therapeutic levels. More recently, the development of the NOACs has allowed alternative methods of anticoagulation. Four such drugs are currently available on the UK market and have been compared with warfarin in patients with non-valvular AF. It is important to remember that although these drugs have been compared in individual trials with warfarin, the populations in each of these studies varied and you would therefore expect a degree of variation in outcomes. In addition, no trial comparing the NOACs head to head has been performed and so it is not appropriate to compare NOACs in this situation.

In the RE-LY study5 dabigatran 150mg twice daily reduced stroke and systemic embolism by 35% compared to warfarin without a significant increase in major bleeding, whereas dabigatran 110mg twice daily was non-inferior to warfarin in terms of stroke or embolism reduction but demonstrated a 20% reduction in major bleeding.

Apixaban, rivaroxaban and edoxaban are factor Xa inhibitors. In the ARISTOTLE trial6, apixaban 5mg twice daily reduced stoke or systemic embolism by 21% compared to warfarin combined with a 31% reduction in major bleeding. The ROCKET-AF trial7 compared rivaroxaban with vitamin K antagonists. Rivaroxaban was non-inferior to warfarin in terms of stroke or embolism and the ENGAGE AF TIMI 48 study8, edoxaban was non-inferior compared to warfarin for stroke and systemic embolism and superior in terms of major bleeding.

In a meta-analysis of the NOAC versus warfarin trials,9 the NOACs appeared overall to reduce the rate of stroke or systemic embolism, death and haemorrhagic stroke versus warfarin at the expense of a slight increase in the rate of gastrointestinal bleeding.

The choice of oral anticoagulation is therefore dependent on the individual patient. NOACs are not suitable for patients with prosthetic heart valves, rheumatic mitral stenosis or severe renal dysfunction. Conversely, NOACs should be first choice in patients who are unable to maintain well controlled INRs while receiving oral vitamin K antagonists.

Rate versus rhythm control

The AFFIRM study10 addressed the approach to rate versus rhythm control in AF. The results of this study suggested no significant difference in all-cause mortality between a rate control strategy versus a strategy to maintain sinus rhythm through anti-arrhythmic therapy such as beta blockers, class 1a anti-arrhythmics and amiodarone. The results would therefore suggest that the only benefit of rhythm control in AF is to improve the patient’s symptoms. Some groups have contested the results of this and other similar studies and have suggested that the benefit of maintaining sinus rhythm may be negated by the negative effects of anti-arrhythmic therapy, giving an overall neutral result, and that alternative mechanisms of maintaining sinus rhythm, such as AF ablation, may therefore have superior results. This area needs further investigation before the use of ablation techniques in routine practice for asymptomatic AF could be considered.

What’s newly available?

Most treatments for AF are widely available in the UK. Newer techniques for invasive AF ablation strategies, such as cryoablation, are developing, making the procedure safer, quicker. They may prove beneficial but are well outside the remit of this article. Novel anti-arrhythmic pharmacology has been limited by its efficacy, or adverse effects.

The most important intervention that has developed recently is the increased screening for asymptomatic AF in the community setting. AF is associated with significant morbidity and mortality. Therefore identification of asymptomatic AF and the delivery of appropriate therapy in the form of anticoagulation and rate control can reduce the rates of ischaemic stroke, heart failure and mortality. Screening has been provided in several modalities such as the, ‘Watch-BP’ monitors that have been placed in GP practices within the UK. These automated BP machines can identify AF at the point of blood pressure measurement in surgery receptions or pharmacies and can trigger practitioners to further assess with a formal ECG. Others have advocated the use of long-term monitoring in high-risk patients such as those with cryptogenic stroke or significant mitral regurgitation or stenosis. The use in these patients of longer-term Holter-style monitors or patient activated devices may prove beneficial.

In addition to screening for asymptomatic AF, the use of NOACs has increased the number of patients who accept anticoagulation who previously were reluctant to use warfarin. Alternatively, some patients opt to continue with warfarin but monitor INR levels through home monitoring. Indeed, NICE have recently advocated this as an option for anti-coagulation in AF. The combination of these two interventions is leading to reductions in ischaemic strokes despite an ageing population.

Dr Dominic Kelly is a consultant cardiologist at the Hampshire Hospitals NHS Foundation Trust, Candover Clinic, Basingstoke and BMI Sarum Road, Winchester.

References

  1. ESC. Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. European Heart Journal, 2016;37:2893–2962
  2. Hart RG, Pearce LA, Aguilar MI. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med 2007;146:857-867
  3. Donze J, Clair C, Hug B et al. Risk of falls and major bleeds in patients on oral anticoagulation therapy. Am J Med 2012;125:773-778.
  4. Man-Son-Hing M, Nichol G, Lau A, Laupacis A. Choosing antithrombotic therapy for elderly patients with atrial fibrillation who are at risk for falls. Arch Intern Med 1999;159:677-685
  5. Connolly SJ, Ezekowitz MD, Yusuf S et al. RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009;361:1139-1151.
  6. Granger CB, Alexander JH, McMurray JJ et al. ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011;365:981-992.
  7. Patel MR, Mahaffey KW, Garg J et al. ROCKET AF Investigators. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011;365:883-891.
  8. Giugliano RP, Ruff CT, Braunwald E et al. Investigators EA-T. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2013;369:2093-2104.
  9. Ruff CT, Giugliano RP, Braunwald E et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet 2014;383:955-962
  10. A Comparison of Rate Control and Rhythm Control in Patients with Atrial Fibrillation. The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) Investigators. N Engl J Med 2002;347:1825-1833

 

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Readers' comments (3)

  • My preference with a new AF patient is to go through the q-stroke and q-bleed web page to added their risk of thromboembolism versus their risk of a bleed in either a native or anticoagulated state. It is surprising how often, when shown the figures, they decline anticoagulation.

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  • Sorry..... Doing this on a phone... Should be "assess" rather than "added"

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  • Very helpful summary, would just add that there is evidence that patients who have AF tend to have more severe strokes as more likely to be a MCA infarct. I remember many cases on the stroke ward with AF who had a MCA infarct and died shortly after.

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