The imminent NICE guidelines for AF – what are the implications?

1. The imminent NICE guidelines for AF – what are the implications? Pulse Live event 2014: Novotel London West One 29th April 2014 David Hargroves, Consultant Physician, Clinical Lead for Stroke Medicine, East Kent Hospitals University NHS Foundation Trust. david.hargroves@nhs.net

2. Disclosures I am principle investigator for 2 industry funded NOAC compliance studies. I have received sponsorship / speaker fees / and or consultancy fees from: BI, Bayer, BMS, Pfizer.

3. Atrial fibrillation: the management of atrial fibrillation NICE guideline Draft for consultation, January 2014 This guidance is an update of NICE clinical guideline 36 (published June 2006) and will replace it when published 11th June 2014

4. Atrial fibrillation (AF) AF is the most common heart rhythm disturbance1 It is estimated 1 in 4 individuals aged 40 years will develop AF1 Due to the aging population, this number is expected to double within 30 years3 4 1. Lloyd-Jones DM, et al. Circulation 2004;110:1042-1046. 2. Decision Resources. Atrial Fibrillation Report. Dec 2008. 3. Go AS, et al. JAMA 2001;285:2370-2375.

5. The prevalence of AF is estimated at 1.3% of the general population and increases sharply with age The average GP: Will have 20–25 cases on their personal list Can expect to diagnose at least 3 new cases per annum In press- Lip G, Heath R. 10 steps before you refer for: ATRIAL FIBRILLATION. British journal of cardiology.

6. Atrial Fibrillation (AF) and Stroke Stroke is the most serious ongoing risk associated with AF1 In patients with AF, blood clots tend to form in the atria, particularly within the left atrial appendage, due to abnormal blood flow and pooling2 These clots may travel to the brain, causing an ischaemic stroke2 1. Wolf PA et al. Stroke 1991;22:983–988; 2. Fuster V et al. Circulation 2006;114:700–752; 3. Paciaroni M et al. Stroke 2007;38:423–430

7. AF increases the risk of stroke AF is associated with a pro-thrombotic state ~5 fold increase in stroke risk 1 Risk of stroke is the same in AF patients regardless of whether they have paroxysmal or sustained AF 2,3 Cardio embolic stroke has a 30-day mortality of 25% 4 AF-related stroke has a 1-year mortality of ~50% 5 1. Wolf PA, et al. Stroke 1991;22:983-988; 2. Rosamond W et al. Circulation. 2008;117:e25–146; 3.Hart RG, et al. J Am Coll Cardiol 2000;35:183-187; 4. Lin H-J, et al. Stroke 1996; 27:1760-1764; 5. Marini C, et al. Stroke 2005;36:1115-1119.

8. Small vessel disease-35% • Large vessel disease-30% • Cardioembolic-35%

9. England Overview Percentage of Ischaemic Strokes that have a diagnosis of AF 38.0% 37.9% 37.7% 37.8% 37.6% 37.4% 37.2% 37.0% 36.8% 36.8% 36.6% 36.4% 36.2% 2009 2010 2011 Publically available HES data 2012

10. Sentinel Stroke National Audit Programme of the Royal College of Physicians* Jan- March 2013 England, Wales, Northern Ireland 11,939 stroke admissions 5,969 in AF Nothing 26% OAC 36% Antiplatelets 38% *www.rcplondon.ac.uk

11. How are AF patients at risk of stroke currently being managed? Preadmission medications in patients with known atrial fibrillation who were admitted with acute ischemic stroke (high-risk cohort, n=597) No antithrombotic29% Sub- therapeuticwarfarin, 29% Dual antiplatelettherapy, 2% Therapeutic warfarin, 10% Single antiplateletagent, 29% 11 Gladstone DJ et al. Stroke 2009;40:235–240.

12. For every 100 patients with AF… Only 60 are diagnosed Of the 58, only 31 are anticoagulated Of the 60, 58 have moderate or high stroke risk Of the 31, only 18 have INRs in range regularly http://www.preventaf-strokecrisis.org/files/files/AF%20Report%208%20Feb%2012.pdf Accessed Jan 2012

13. New oral anticoagulants Initiation phase XII IX X XI Platelet Surface Amplification Propagation phase VIII Warfarin Rivaroxaban Apixaban Xa Thrombin activity Common Pathway Dabigatran etexilate Thrombin Fibrinogen Fibrin

14. Diagnosis of AF Personalised package of care and information Stroke prevention Continued symptoms? Rate control strategies Rhythm control strategies Ablation strategies Monitoring NICE AF draft guidance (January 2014)

15. Personalised package of care and information • Measures to prevent stroke • Rate control • Assessment of symptoms for rhythm control • Psychological support if needed • Up-to-date and comprehensive education and information on: • Cause, effects and possible complications of atrial fibrillation • Management of rate and rhythm control • Anticoagulation • Practical advice on anticoagulation in line with recommendation 1.3.1 in ‘Venous thromboembolic diseases’ (NICE clinical guideline 144) • Support networks. [new 2014] NICE AF draft guidance (January 2014)

16. Stroke risk assessment with CHA2DS2-VASc 1 Lip GYH et al.Stroke 2010;41:2731–2738. 2 Olesen JB et al BMJ 2011, 342: d124 NICE AF draft guidance (January 2014)

17. ESC 2012 AF stroke prevention guidelines AF paroxysmal, persistent or permanent Non-valvular Valvular* No antithrombotic therapy Aged <65 years, no cardiovascular disease Dose-adjusted VKA (INR 2.0–3.0) CHA2DS2-VASc Preferred option Less preferable or less validated 1† ≥2 Options not well validated OAC therapy Assess bleeding risk (HAS-BLED) Consider patient values and preferences CHA2DS2-VASc:1 and not suitable for, or refusing, NOAC or VKA CHA2DS2-VASc: 2 refusing OAC CHA2DS2-VASc: 2 unsuitable for OAC Suitable for OAC therapy Dose-adjusted VKA (INR 2.0–3.0) Consider aspirin + clopidogrel or aspirin only‡ NOAC drugs§ Apixaban Dabigatran Rivaroxaban Consider aspirin + clopidogrel or aspirin only‡ Consider LAAO, or LAA excision Camm AJ et al. Europace 2012;14(10):1385–413, European Heart Journal (2012) 33, 2719–2747. Page 2726 – 4.4 fig 1

18. Anticoagulation for stroke prevention • Offer first line anticoagulation to all patients with CHADsVaSc ≥2 and consider in males ≥1 [new 2014] • Anticoagulation may be with apixaban, dabigatran etexilate, rivaroxaban or a vitamin K antagonist [new 2014] • Recommendations for use of NOACs are in line with the relevant Technology Appraisals [new 2014] • Do not withhold anticoagulation solely because the person is at risk of having a fall [new 2014] Do not offer aspirin monotherapy solely for stroke prevention to people with atrial fibrillation [new 2014] Only consider dual antiplatelet therapy with aspirin and clopidogrel for stroke prevention if anticoagulation is contraindicated or not tolerated and the person has a CHA2DS2-VASc score of 2 or above [new 2014] NICE AF draft guidance (January 2014)

19. NICE AF stroke prevention guidelines (draft 2014) AF paroxysmal, persistent or permanent Non-valvular Valvular* No antithrombotic therapy Aged <65 years, no cardiovascular disease Dose-adjusted VKA (INR 2.0–3.0) CHA2DS2-VASc Preferred option Less preferable or less validated 1† ≥2 Options not well validated OAC therapy Assess bleeding risk (HAS-BLED) Consider patient values and preferences CHA2DS2-VASc:1 and not suitable for, or refusing, NOAC or VKA CHA2DS2-VASc: 2 refusing OAC Suitable for OAC therapy Dose-adjusted VKA (INR 2.0–3.0) Consider aspirin + clopidogrel NOAC drugs§ Apixaban Dabigatran Rivaroxaban Consider aspirin + clopidogrel NICE AF draft guidance (January 2014)

20. Assess bleeding risk HAS-BLED bleeding risk score For people with an increased risk of bleeding the benefit of anticoagulation may not always outweigh the bleeding risk, and careful monitoring of bleeding risk is important [new 2014] Correct and monitor: • uncontrolled hypertension • poor control of INR (‘labile INRs’) • concurrent medication, for example concomitant use of aspirin or an NSAID • harmful alcohol consumption [new 2014] OAC benefits outweigh bleeding risk for most people NICE AF draft guidance (January 2014)

21. Balancing risk using theCHA2DS2-VASc and HAS-BLED scores CHA2DS2–VASc 0–2 p CHA2DS2–VASc ≥3 p 1.0 1.0 OAC 0.8 0.8 OAC 0.6 0.6 HAS-BLED ≥3 p 0.4 0.4 No OAC P<0.00001(n=1.787) P<0.00001(n=59.817) No OAC 0.2 0.2 0 0 Risk for intracranial bleeding 1.0 1.0 OAC OAC 0.8 0.8 No OAC 0.6 0.6 HAS-BLED 0–2 p 0.4 0.4 No OAC P<0.00001(n=43.395) P<0.00001(n=53.797) 0.2 0.2 0 0 0 1 2 3 4 0 1 2 3 4 Years Risk for embolic stroke Friberg L, Rosenqvist M, Lip GY.. Circulation 2012;125:2298–307

22. Assessing anticoagulation control with VKAs • Calculate the person’s time in therapeutic range (TTR) at each visit • When calculating TTR: • Use a validated method of measurement such as the Rosendaal method for computer-assisted dosing or proportion of tests in range for manual dosing • Exclude measurements taken during the first 6 weeks of treatment • Calculate TTR over a maintenance period of at least 6 months [new 2014] NICE AF draft guidance (January 2014)

23. Assessing anticoagulation control with VKAs Reassess anticoagulation for a person with poor anticoagulation control shown by any of the following: • 2 INRs >5 or 1 INR >8 in past 6/12 • 2 INRs <1.5 in past 6 months • TTR less than 65%. [new 2014] NICE AF draft guidance (January 2014)

24. Reassessing anticoagulation • Take into account and if possible correct the following factors: • Cognitive function • Adherence to prescribed therapy • Illness • Interacting drug therapy • Lifestyle factors including diet and alcohol consumption. [new 2014] • If poor anticoagulation control cannot be improved, evaluate the risks and benefits of alternative stroke prevention strategies and discuss these with the person. [new 2014] NICE AF draft guidance (January 2014)

25. People with AF not taking an anticoagulant Review stroke risk when they reach age 65 or if they develop any of the following at any age: • Diabetes • Heart failure • Peripheral arterial disease • Coronary heart disease • Stroke, transient ischaemic attack or systemic thromboembolism [new 2014] NICE AF draft guidance (January 2014)

26. Rate and rhythm control Assess and offer rate control as the first line strategy for all people with AF [new 2014] • Initial monotherapy with β-blocker or rate-limiting CCB • Digoxin monotherapy only for non-paroxysmal AF in sedentary patients [new 2014] • If monotherapy does not control symptoms, combine 2 of : • β-blocker • Diltiazem • Digoxin [new 2014] • Do not offer amiodarone for long term rate control [new 2014] NICE AF draft guidance (January 2014)

27. Rate and rhythm control • Offer rhythm control to people with or without continuing symptoms if they have any of the following: • AF with a reversible cause • Heart failure thought to be primarily caused by AF • New-onset AF [new 2014] NICE AF draft guidance (January 2014)

28. Rate and rhythm control Consider pharmacological and/or electrical rhythm control for people with atrial fibrillation whose symptoms continue after heart rate has been controlled or a rate-control strategy has not been successful • Electrical Cardioversion (ECV) if AF persisted > 48hrs • Consider amiodarone 4 weeks before and 12 months after ECV to maintain sinus rhythm • TOE guided and conventional ECV considered equally effective • Offer β-blocker (e.g. sotalol) for long-term rhythm control if needed NICE AF draft guidance (January 2014)

29. Rate and rhythm control Consider pharmacological and/or electrical rhythm control for people with atrial fibrillation whose symptoms continue after heart rate has been controlled or a rate-control strategy has not been successful If β-blockers unsuccessful or contraindicated….. LV impairment or heart failure Structural heart disease Consider amiodarone Do not offer flecainide or propafenone* NICE AF draft guidance (January 2014) *increased risk of ventricular arrhythmias

30. Referral for specialised management Refer people promptlyat any stage if treatment fails to control the symptoms of atrial fibrillation and referral for more specialised management is needed. [new 2014] NICE AF draft guidance (January 2014)

31. Left atrial ablation • If drug treatment has failed to control symptoms of atrial fibrillation or is unsuitable: • offer left atrial catheter ablation to people with paroxysmal atrial fibrillation • consider left atrial surgical or catheter ablation for people with persistent atrial fibrillation • discuss the risks and benefits with the person[new 2014] NICE AF draft guidance (January 2014)

32. Atrial fibrillation: the management of atrial fibrillation NICE guideline Draft for consultation, January 2014 This guidance is an update of NICE clinical guideline 36 (published June 2006) and will replace it when published 11th June 2014

33. NICE AF stroke prevention guidelines (draft 2014) AF paroxysmal, persistent or permanent Non-valvular Valvular* No antithrombotic therapy Aged <65 years, no cardiovascular disease Dose-adjusted VKA (INR 2.0–3.0) CHA2DS2-VASc Preferred option Less preferable or less validated 1† ≥2 Options not well validated OAC therapy Assess bleeding risk (HAS-BLED) Consider patient values and preferences CHA2DS2-VASc:1 and not suitable for, or refusing, NOAC or VKA CHA2DS2-VASc: 2 refusing OAC Suitable for OAC therapy Dose-adjusted VKA (INR 2.0–3.0) Consider aspirin + clopidogrel NOAC drugs§ Apixaban Dabigatran Rivaroxaban Consider aspirin + clopidogrel NICE AF draft guidance (January 2014)

34. david.hargroves@nhs.net The imminent NICE guidelines for AF – what are the implications?