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

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 11 th June 2014

4. 4 Atrial fibrillation (AF) AF is the most common heart rhythm disturbance 1 It is estimated 1 in 4 individuals aged 40 years will develop AF 1 Due to the aging population, this number is expected to double within 30 years 3 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 AF 1 In patients with AF, blood clots tend to form in the atria, particularly within the left atrial appendage, due to abnormal blood flow and pooling 2 These clots may travel to the brain, causing an ischaemic stroke 2 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.  Large vessel disease-30% Cardioembolic-35%  Small vessel disease-35%

9. England Overview Publically available HES data 2012 Percentage of Ischaemic Strokes that have a diagnosis of AF 36.2% 36.4% 36.6% 36.8% 37.0% 37.2% 37.4% 37.6% 37.8% 38.0% 200920102011 37.9% 37.7% 36.8%

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

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

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

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

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

15. Personalised package of care and information NICE AF draft guidance (January 2014)  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]

16. Stroke risk assessment with CHA 2 DS 2 -VASc CHA 2 DS 2 -VASc criteriaScore Congestive heart failure/ left ventricular dysfunction 1 Hypertension1 Age  75 yrs 2 Diabetes mellitus1 Stroke/transient ischaemic attack/TE2 Vascular disease (prior myocardial infarction, peripheral artery disease or aortic plaque) 1 Age 65–74 yrs1 Sex category (i.e. female gender) 1 CHA 2 DS 2 -VASc total score Rate of stroke/other TE (%/year)* 0 0.78 1 2.01 2 3.71 3 5.92 4 9.27 5 15.26 6 19.74 7 21.50 8 22.38 923.64 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 Consider aspirin + clopidogrel or aspirin only ‡ Consider LAAO, or LAA excision CHA 2 DS 2 -VASc:1 and not suitable for, or refusing, NOAC or VKA CHA 2 DS 2 -VASc:  2 refusing OAC Consider aspirin + clopidogrel or aspirin only ‡ Non-valvular CHA 2 DS 2 -VASc No antithrombotic therapy Aged <65 years, no cardiovascular disease CHA 2 DS 2 -VASc:  2 unsuitable for OAC Dose-adjusted VKA (INR 2.0 – 3.0) NOAC drugs § Apixaban Dabigatran Rivaroxaban 1†1† ≥2 OAC therapy Assess bleeding risk (HAS-BLED) Consider patient values and preferences Suitable for OAC therapy Dose-adjusted VKA (INR 2.0–3.0) Valvular* AF paroxysmal, persistent or permanen t Camm AJ et al. Europace 2012;14(10):1385–413, European Heart Journal (2012) 33, 2719–2747. Page 2726 – 4.4 fig 1 Options not well validated Less preferable or less validated Preferred option

18.  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] Anticoagulation for stroke prevention 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 CHA 2 DS 2 -VASc score of 2 or above [new 2014] NICE AF draft guidance (January 2014)

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

20. OAC benefits outweigh bleeding risk for most people 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]  uncontrolled hypertension  poor control of INR (‘labile INRs’)  concurrent medication, for example concomitant use of aspirin or an NSAID  harmful alcohol consumption [new 2014] Correct and monitor: HAS-BLED bleeding risk score Assess bleeding risk NICE AF draft guidance (January 2014)

21. Friberg L, Rosenqvist M, Lip GY.. Circulation 2012;125:2298–307 Balancing risk using the CHA 2 DS 2 -VASc and HAS-BLED scores 0 0.2 0.4 0.6 0.8 1.0 HAS-BLED ≥3 p 0 0.2 0.4 0.6 0.8 1.0 01234 0 0.2 0.4 0.6 0.8 1.0 0 0.2 0.4 0.6 0.8 1.0 01234 Years HAS-BLED 0–2 p CHA 2 DS 2 –VASc 0–2 pCHA 2 DS 2 –VASc ≥3 p Risk for intracranial bleeding Risk for embolic stroke P<0.00001 (n=1.787) P<0.00001 (n=43.395) P<0.00001 (n=59.817) P<0.00001 (n=53.797) No OAC OAC No OAC OAC

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.  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] Reassess anticoagulation for a person with poor anticoagulation control shown by any of the following: Assessing anticoagulation control with VKAs 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.  Diabetes  Heart failure  Peripheral arterial disease  Coronary heart disease  Stroke, transient ischaemic attack or systemic thromboembolism [new 2014] 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: 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  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] [new 2014] NICE AF draft guidance (January 2014)

27. 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] Rate and rhythm control NICE AF draft guidance (January 2014)

28. Rate and rhythm control 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 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 LV impairment or heart failure Consider amiodarone If β-blockers unsuccessful or contraindicated….. Structural heart disease Do not offer Do not offer flecainide or propafenone* *increased risk of ventricular arrhythmias NICE AF draft guidance (January 2014)

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

31. 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] Left atrial ablation 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 11 th June 2014

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

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