Dr Dipankar Dutta discusses key updated NICE recommendations on stroke assessment and prevention in atrial fibrillation

People with atrial fibrillation (AF) are five times more likely to have a stroke compared with those in sinus rhythm.1 Strokes in patients with AF are more severe and have a higher mortality.2 About 1.6%–2% of the general population in England3 and nearly 10% of people over 80 years of age4 have AF. National stroke audits show that only 36% of patients admitted to stroke units with cardio-embolic stroke due to AF were previously on anticoagulants.5 Much of the morbidity and mortality from AF can be prevented by optimal management.

Several new recommendations have been incorporated into the latest NICE guideline on the management of AF (Clinical Guideline [CG] 180, see www.nice.org.uk/guidance/CG180) released in June 2014.6 The full guideline, published by the National Clinical Guideline Centre, contains details of the methods and evidence used to develop the guideline.3 The guideline has the potential to significantly change management in both primary and secondary care and improve stroke prevention. In this article, I have focused on the updated recommendations and the key points and implications for primary care and commissioners.

New NICE recommendations for stroke prevention in people with AF

The updated guideline now recommends the assessment of stroke risk using the CHA2DS2-VASc7 score and bleeding risk using the HAS-BLED8 score.

Using CHA2DS2-VASc to assess stroke risk

The CHA2DS2-VASc7 stroke risk score should be used in people with paroxysmal, persistent, or permanent AF (regardless of symptoms), atrial flutter, and people with continuing risk of AF recurrence after cardioversion. The widely used CHADS2 score9 was not very good at classifying people at the lower end of the risk scale and the CHA2DS2-VASc score is better at refining stroke risk in people previously thought to be at low risk.7,10 More people will be eligible for anticoagulation using CHA2DS2-VASc.11

Assessment of bleeding risk using HAS-BLED

A major dilemma with the use of oral anticoagulation is balancing stroke reduction against the risk of serious bleeding (especially intracranial haemorrhage). For the first time, the use of a bleeding risk score has been advocated. The HAS-BLED8 score should be used to assess the risk of bleeding in people who are starting anticoagulation. Use of the score prompts users to identify bleeding risk factors which, in some instances, may be modifiable. It must be emphasised that the HAS-BLED has a poor to fair discriminatory power in validation studies and is not primarily intended to deny people anticoagulants but to identify modifiable risk factors, such as hypertension, high alcohol intake, and the use of concurrent aspirin and NSAIDs, that could be addressed.12 In most instances, the risk of stroke will outweigh the bleeding risk and preventing strokes will take priority over avoidance of a bleed.6

Choice of intervention

Should aspirin be used for stroke prevention in AF?

Aspirin does not reduce mortality or systemic emboli in AF.3,13 It does have a modest benefit in reducing ischaemic stroke, partly offset by increased bleeding and haemorrhagic stroke risk.1,3 The BAFTA study showed that the bleeding risk of aspirin in the elderly was broadly similar to that of warfarin.14 Aspirin is therefore no longer recommended for stroke prevention in AF. Aspirin may, however, still be used during the first 2 weeks after onset of ischaemic stroke (as prognosis is improved in early ischaemic stroke),15,16 and in situations where it is needed for other conditions such as MI.3

Anticoagulation and stroke prevention

NICE CG180 (the full guideline) includes an algorithm that will support the healthcare professional in determining who to recommend antithrombotics to and which drugs to use, based on the CHA2DS2-VASc score (see Algorithm 1 on p.42 of the full guideline).3

For patients at low risk of stroke, where anticoagulation was not indicated, the economic model used by NICE suggested that a higher quality adjusted life years (QALY) gain could be achieved by not offering any therapy (i.e. aspirin) at all.3

Anticoagulation for AF reduces mortality as well as ischaemic strokes and prevents systemic emboli.3,17

Anticoagulation and falls

Another major update is laying to rest the myth of falls as a contraindication to anticoagulation. Falls do not usually cause significant (particularly intracranial) bleeds and patients should not be denied anticoagulation solely because they have fallen.18,19

Novel oral anticoagulants

The guideline does not directly recommend novel oral anticoagulants (NOACs) over warfarin but refers the reader to the NICE single technology appraisals (TAs) for each NOAC:20-22

All the options for anticoagulation should be considered and the advantages and disadvantages of the different treatments available discussed with the patient before choosing a particular drug.6 The patient should only be commenced on a particular NOAC if he or she fulfils the eligibility criteria described in the TA for that particular drug. The TAs state that the NOACs should be used in non-valvular AF with one or more risk factors:20-22

  • for apixaban and rivaroxaban: prior stroke or TIA, age 75 years or older, hypertension, diabetes, heart failure
  • for dabigatran: previous stroke/TIA or systemic embolus, left ventricular ejection fraction below 40%, symptomatic heart failure, age 75 years or older, age 65 years or older with diabetes/coronary artery disease/hypertension.

For people who are taking warfarin, the potential risks and benefits of switching to a NOAC should be considered in light of their level of INR control. For a review of NOACs, see Guidelines in Practice. 23

The NOACs are often used by stroke physicians in preference to warfarin in patients with a recent TIA (after neuroimaging) because of their quick onset of action and immediate protective effect.

Vitamin K antagonists

Warfarin continues to be an effective first-line option. The guideline emphasises the importance of assessing anticoagulation control with the VKAs and recommends the calculation of individual time in therapeutic range (TTR) at each visit using a validated method of measurement, such as the Rosendaal method,24 for computer assisted dosing or TTR for manual dosing. Poor control can be indicated by two INR values higher than 5 or one INR value higher than 8 within the past 6 months or two INR values less than 1.5 within the past 6 months or TTR less than 65%. If poor anticoagulation control cannot be improved, the risks and benefits of alternative stroke prevention should be considered.6

Referral and specialised management

The guideline emphasises the importance of secondary care referral at any stage if treatment fails to control the symptoms of atrial fibrillation and if more specialised management is needed.6

Prompt referral is defined as no longer than 4 weeks after the final failed treatment or no longer than 4 weeks if atrial fibrillation recurs after cardioversion and further specialised management is needed.

When should left atrial appendage occlusion be considered?

The guideline presents a relatively new option, left atrial appendage occlusion (LAAO), if anticoagulation is contraindicated or not tolerated, and suggests discussing the benefits and risks of LAAO with patients who face this situation.

The left atrial appendage is the major source of thrombus-causing stroke and peripheral thromboembolism in patients with AF.25 Catheter-based techniques for closure or obliteration of the left atrial appendage are now an option for stroke prevention.26-28 In patients who cannot take anticoagulants, but have a high risk of stroke, LAAO should be considered as a potentially cost-effective intervention.6 The short-term risks for this procedure include cardiac tamponade, thromboembolism and device embolisation.28 In the trials of LAAO, patients were maintained on antiplatelets in the long term and in one study patients were given warfarin for several days at the time of device implantation.

Annual review of stroke and anticoagulant risk

The guideline advocates annual reviews for all people with AF to assess stroke and bleeding risks. For people not taking an anticoagulant, stroke risk should be reviewed when they reach the age of 65 or if they develop a stroke, TIA, systemic embolism, diabetes, heart failure, peripheral vascular disease, or coronary artery disease at any age. For people who are taking anticoagulants, the quality of anticoagulation should be reviewed at least annually, or more often if they develop conditions that affect anticoagulation or bleeding risk. All reviews and decisions should be carefully documented.

Implications for primary care

Most AF is likely to be detected in primary care. Manual palpation of the pulse will be needed for patients presenting with cardiovascular symptoms, presyncope or syncope, symptoms of stroke and TIA, and opportunistically in asymptomatic older people. Arrhythmia-detecting blood pressure monitors may prove useful.29 The CHA2DS2-VASc score will have to be used for risk stratification and more patients will be eligible for anticoagulation. Aspirin will no longer be an option for thromboprophylaxis. Patients currently on aspirin for AF will have to be reviewed and alternative anticoagulation considered. Patients already on warfarin will need assessments of the TTR and a possible switch to NOACs. General practitioners will have to become increasingly familiar with the NOACs and referrals to secondary care may increase. Annual reviews for patients in AF may add to the workload.

Implications for commissioners

This guideline will affect both NHS England and Clinical Commissioning Groups (CCGs). The annual cost of drugs used instead of aspirin (and as a result of using CHA2DS2-VASc) has been estimated as £88,000 for a population of 100,000.11 The use of the CHA2DS2-VASc score will lead to an estimated 200 extra patients anticoagulated per 100,000.11 The future use of NOACs is estimated to rise from the current 14% (of people with AF) to 35%.11 There will be greater costs associated with increased referrals to secondary care and referrals for LAAO.

Conclusion

The main barriers to effective anticoagulation for AF have been a fear of causing bleeds and the belief that antiplatelets are a lower-risk, albeit less effective alternative. Older people, the group at highest risk of stroke, have been denied anticoagulation because of a perception of greater risk of bleeds in this group and an exaggerated fear about the risk of bleeding in people who fall. The new NICE guideline now reinforces that aspirin should not be used as stroke prevention in people with AF. They remind us that anticoagulation with either a VKA or NOACs is the thromboprophylaxis of choice in all forms of AF, atrial flutter, and people who are at risk of relapse after cardioversion. NOACs are a welcome addition to our therapeutic armamentarium and should enable more people to be safely anticoagulated than ever before. In high-risk patients who cannot have anticoagulants, LAAO is now a recommended option.

This guideline is very likely to lead to significant change in practice for both primary and secondary care and reduced morbidity and mortality from thromboembolic stroke. Full implementation of this guideline may result in a reduction of stroke risk in AF to 69% of the current level, which equates to an estimated 10,000 fewer strokes in England due to AF every year.11

  1. Hart R, Pearce L, Aguilar M. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med 2007; 146 (12): 857–867.
  2. Lin H, Wolf P, Kelly-Hayes M et al. Stroke severity in atrial fibrillation. The Framingham Study. Stroke 1996; 27: 1760–1764.
  3. National Clinical Guideline Centre. Atrial fibrillation: the management of atrial fibrillation. Clinical guideline: Methods, evidence and recommendations. London: NICE, 2014. Available at: nice.org.uk/guidance/cg180/resources/cg180-atrial-fibrillation-update-full-guideline3
  4. Go A, Hylek E, Phillips K et al. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA 2001; 285: 2370–2375.
  5. Royal College of Physicians Clinical Effectiveness and Evidence Unit on behalf of the Intercollegiate Stroke Working Party. Sentinel Stroke National Audit Programme (SSNAP ) public report. 2014.
  6. NICE. Atrial fibrillation: the management of atrial fibrillation. Clinical Guideline 180. London: NICE, 2014. Available at: www.nice.org.uk/guidance/CG180
  7. Lip G, Nieuwlaat R, Pisters R et al. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation. Chest 2010; 137: 263–272.
  8. Pisters R, Lane D, Nieuwlaat R et al. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest 2010; 138: 1093–1100.
  9. Gage B, Waterman A, Shannon W et al. Validation of clinical classification schemes for predicting stroke: results from the National Registry of Atrial Fibrillation. JAMA 2001; 285: 2864–2870.
  10. Coppens M, Eikelboom J, Hart R et al. The CHA2DS2-VASc score identifies those patients with atrial fibrillation and a CHADS2 score of 1 who are unlikely to benefit from oral anticoagulant therapy. Eur Heart J 2013; 34: 170–176.
  11. NICE. Putting NICE guidance into practice. Costing report: atrial fibrillation. Implementing the NICE guideline on atrial fibrillation. Clinical Guideline 180. NICE, 2014. Available at: www.nice.org.uk/Guidance/CG180
  12. Lane D, Lip G. Use of the CHA(2)DS(2)-VASc and HAS-BLED scores to aid decision making for thromboprophylaxis in nonvalvular atrial fibrillation. Circulation 2012; 126: 860–865.
  13. Petersen P. Placebo-controlled, randomised trial of warfarin and aspirin for prevention of thromboembolic complications in chronic atrial fibrillation. The Copenhagen AFASAK study. Lancet 1989; 333: 175–179.
  14. Mant J, Hobbs F, Fletcher K et al. Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): a randomised controlled trial. Lancet 2007; 370: 493–503.
  15. The International Stroke Trial (IST): a randomised trial of aspirin, subcutaneous heparin, both, or neither among 19435 patients with acute ischaemic stroke. International Stroke Trial Collaborative Group. Lancet 1997; 349: 1569–1581.
  16. CAST: randomised placebo-controlled trial of early aspirin use in 20,000 patients with acute ischaemic stroke. CAST (Chinese Acute Stroke Trial) Collaborative Group. Lancet 1997; 349: 1641–1649.
  17. Aguilar M, Hart R, Pearce L. Oral anticoagulants versus antiplatelet therapy for preventing stroke in patients with non-valvular atrial fibrillation and no history of stroke or transient ischemic attacks. Cochrane database Syst Rev 2007; CD006186.
  18. Man-Son-Hing M, Laupacis A. Anticoagulant-related bleeding in older persons with atrial fibrillation: physicians’ fears often unfounded. Arch Intern Med 2003; 163: 1580–1586.
  19. Donzé 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.
  20. NICE. Dabigatran etexilate for the prevention of stroke and systemic embolism in atrial fibrillation. Technology Appraisal 249. NICE, 2012. Available at: www.nice.org.uk/guidance/TA249
  21. NICE. Rivaroxaban for the prevention of stroke and systemic embolism in people with atrial fibrillation. Technology Appraisal 256. NICE, 2012. Available at: www.nice.org.uk/guidance/TA256
  22. NICE. Apixaban for preventing stroke and systemic embolism in people with nonvalvular atrial fibrillation. Technology Appraisal 275. NICE, 2013. Available at: www.nice.org.uk/guidance/TA275
  23. Apostolakis S, Kirchhof P. Novel anticoagulants bring stroke prevention therapy to more people. Guidelines in Practice 2014; 17 (1): 25–34.
  24. Rosendaal F, Cannegieter S, van der Meer F, Briët E. A method to determine the optimal intensity of oral anticoagulant therapy. Thromb Haemost 1993; 69: 236–239.
  25. Blackshear J, Odell J. Appendage obliteration to reduce stroke in cardiac surgical patients with atrial fibrillation. Ann Thorac Surg 1996; 61: 755–759.
  26. Holmes D, Reddy V, Turi Z. Percutaneous closure of the left atrial appendage versus warfarin therapy for prevention of stroke in patients with atrial fibrillation: a randomised non-inferiority trial. Lancet 2009; 374: 534–542.
  27. Reddy V, Doshi S, Sievert H. Percutaneous left atrial appendage closure for stroke prophylaxis in patients with atrial fibrillation: 2.3-year follow-up of the PROTECT AF (Watchman Left Atrial Appendage System for Embolic Protection in Patients with Atrial Fibrillation) trial. Circulation 2013; 127: 720–729.
  28. Lewalter T, Ibrahim R, Albers B, Camm A. An update and current expert opinions on percutaneous left atrial appendage occlusion for stroke prevention in atrial fibrillation. Europace 2013; 15: 652–656.
  29. Stergiou G, Karpettas N, Protogerou A et al. Diagnostic accuracy of a home blood pressure monitor to detect atrial fibrillation. J Hum Hypertens 2009; 23: 654–658. G