1. MANAGEMENT OF ATRIAL FIBRILLATION Mary N. Healy, MS, ARNP-BC Heart & Vascular Center of Sarasota

2. OBJECTIVES 1. Define the difference between paroxysmal and persistent Atrial Fibrillation 2. State the CVA risk per year of a 68 yr old female with hypertension that presents with new onset paroxysmal atrial fibrillation 3. Discuss two reasons to pursue rhythm control over rate control 4. Name 2 patient conditions in which warfarin is the only safe consideration for thromboembolic events in AF 5. Idenitify one drug that can be used for pharmacologic cardioversion to restore normal sinus rhythm

3. Pearls of AF Management Address underlying triggers Hyperthyroidism, hypertension, obesity, alcohol, OSA, U/LRI Everyone needs rate control (to improve symptoms & prevent tachycardia related cardiomyopathy) <80 at rest and <110 most simple activity-assess with Holter monitor Use beta blocker if pt has CHF or CAD Use non-dihydropyridine CCB in those with COPD or asthma If more rate control needed, add digoxin Rate vs Rhythm control AFFIRM and RACE trials showed that mortality rates were slightly better with rate control. However the exceptions are: <65, those with CHF, those with persistent symptoms despite rate control

4. Pearls of AF Management Drugs or Ablation for Rhythm Control Opportunity for shared decision-making. Ablation more successful, but is associated with more risk. If drugs not successful, follow with ablation. Amiodarone has benefit of both rate and rhythm control, but has serious potential side effects When to Anticoagulate and What Drug to Use Make life easy, download an app to your phone to figure CHA 2 DS 2 VASc & HAS-BLED score https://itunes.apple.com/us/app/cardio- calculator/id955390696?mt=8 https://itunes.apple.com/us/app/cardio- calculator/id955390696?mt=8 CHA 2 DS 2 VASc of 2 or more and HAS-BLED score of < or = 3 warrant anticoagulation with warfarin or a novel oral anticoagulant

5. APP for Thromboembolic Risk

6. Pearls of AF Management Use warfarin in those with valve replacement, mitral stenosis, end- stage kidney disease or on dialysis If you use a novel anti-coagulant with chronic kidney disease, the dose needs to be reduced In the elderly with the novel agents, periodically re-evaluate renal function do determine if dosage changes should be made Dual antiplatelet therapy (aspirin + clopidogrel) is no longer recommended due to risk of bleeding

7. INTRODUCTION TO AF

8. Incidence/Scope of the Problem Mechanisms causing AF are multi-factoral, making it a complex and many times difficult for practitioners to manage. Symptoms range from non-existent to severe. Frequent hospitalizations, thromboembolic events, hemodynamic disruptions result in significant morbidity and mortality.

9. Scope of Problem Stroke/CHF/Dementia Risk 5 fold increase risk of stroke, and stroke risk increases with age AF related stroke is likely to be more severe than non-AF stroke 3 fold risk of CHF 2 fold increased risk of dementia as well as death

10. Scope of Problem Costs Hospitalizations with AF as the primary diagnosis accounts for >467K admits in the US. >100K deaths/year Pts. with AF are twice as likely to be hospitalized & 3 times more likely to have multiple hospitalizations Treating pts. with AF adds ~$26 billion to the US healthcare bill annually. Affects 6.1 million American adults and is expected to double in the next 25 years.

11. Definition of Atrial Fibrillation AF is a supraventricular tachyarrhythmia with uncoordinated and ineffective atrial contraction Characterized by; Irregular R-R intervals Absence of P waves Irregular atrial activity (fibrillation waves)

14. Mechanisms of Atrial Fibrillation

15. Patient Assessment Triggers of AF Hyperthyroid ETOH use Recent Pulm. Infection OSA Smoking Immediate post-surgery Inordinate Stress Electrolyte Imbalance Risk Factors Increasing Age European ancestry FH/Genetics LVH/LAE/Mitral Valve Dis. CHF DM MI HTN Obesity

16. Patient Assessment Chief Complaint May be asymptomatic especially if >65 yr. Fatigue Palpitations SOB Dizziness Syncope Frequent urination Physical Findings Irregular pulse Irregular JVP Variation of intensity of S1 May also find: CHF symptoms Valvular murmur of MR or MS

17. Suggested Treatment Algorithm

19. REDUCING THROMBOTIC RISK

20. Priority #1 in AF/Reduce Embolic Risk Therapy based on shared decision making Base on risk of TE risk regardless of pattern (paroxysmal, permanent, etc) In non-valvular AF, CHA 2 DS 2 -VASc is recommended assessment of CVA risk For pts with artificial heart valves, warfarin is recommended. Balancing the Risks and Benefits Non-valvular AF increases CVA risk x5. AF in presence of mitral stenosis, increases CVA risk x 20 over those in NSR

21. 90% of strokes from AF are caused by a clot in the left atrial appendage

23. Antithrombotic Options Prevent strokes and systemic emboli in part by reducing the formation of platelet rich or thrombotic clots in the LA or LA appendage Clinical Trials have looked at Warfarin vs aspirin; aspirin with warfarin or clopidogrel (Plavix®) and aspirin; warfarin vs. aspirin and clopidogrel; warfarin vs. direct thrombin inhibitors (dabigatran-Pradaxa®); warfarin vs. Xa inhibitors (Apixaban-Eliquis® & rivaroxaban-Xarelto®)

24. Coag Cascade and Antithrombotics

25. Warfarin Vitamin K antagonist (VKA) in use since the 1950’s. Works on multiple sites of the coagulation cascade- Factor IX, VII, X, II Pros Inexpensive, available as generic When INR therapeutic, significant risk reduction in stroke risk Cons Narrow therapeutic window Increased risk of serious bleeding, including brain Interaction with other drugs Effects of alterations in diet Freq. blood tests- therapeutic range achieved only ~55% of time

26. Dabigatran Direct Thrombin Inhibitor 150mg BID superior to warfarin in stroke, systemic embolism. Hemorrhagic strokes, less, but major bleeds- non inferior to warfarin. Average CHADS score 2.1 Also available 75mg BID for CrCl 15-30 mL/min-this dose never studied. Pros No blood testing No drug or dietary interaction Cons BID dosing High price

27. Rivaroxaban Direct factor Xa inhibitor (excreted by kidneys) Studied older pts and mean CHADS score was 3.47 Non-inferior to warfarin in stroke risk and major bleeding, but did have less fatal bleeding and less brain bleeds. Dose is 20mg daily with evening meal for CrCl>50mL/min or 15mg for CrCl 30-49mL/min Pros No blood testing Once daily dosing (though is with evening meal) Minimal drug and no dietary interactions Cons Expensive

28. Apixaban Direct factor Xa inhibitor (eliminated hepatically and highly protein bound) Significantly better than warfarin in reducing strokes (both ischemic and hemorrhagic), systemic emboli and major bleed events. Fewer deaths than warfarin Average CHADS 2.1, mean age 70 Dosing-5mg bid unless meet two of the following: age > or = to 80, weight =1.5mg/dL, then 2.5mg bid Pros and Cons Similar to the other novel anticoagulants

29. General considerations in choosing anticoagulants If stable on warfarin and pt is happy with blood testing, etc, no need to change Medicare pts are covered if they wish, to do home monitoring checks-may increase the time in therapeutic range Reversing warfarin: Aquamephyton (Vitamin K) usually po, is available IV, takes several hours to reverse FFP infusion, time to reverse

30. Anticoag Considerations, cont’d If warfarin chosen as anticoagulant, it will take AT LEAST 5 days, and probably longer to achieve therapeutic INR, strongly consider using subq heparin, or enoxaparin to bridge until therapeutic Pt education required to counsel on testing, drug & food interactions Novel anticoagulants are approved in AF for “non- valvular” AF. Also approved for other indications, DVT, PE, but NOT FOR METAL VALVES Rapid onset and offset of action so bridging is usually not needed. Strict compliance with new agents is critical

32. Role of Antiplatelets Limited data on the benefit of aspirin In primary prevention of stroke in AF, may reduce risk by 0.8%/yr (# needed to treat-125) For secondary prevention in those with TIA or strokes aspirin associated with risk reduction of 2.5%/year (# needed to treat-40) These data based on meta analysis. In the study that showed the most benefit, 325mg dose was used Aspirin ineffective in preventing strokes in those >75 and did not prevent severe strokes Clopidogrel + aspirin Better than aspirin alone, but benefits are tempered by a significant increase in major bleeding events Studies show clear benefit of warfarin over C+A and Eliquis over C+A

33. HAS-BLED score for bleeding risk on oral anticoagulation in atrial fibrillation Feature Score if present HTN (Systolic ≥ 160mmHg) 1 Abnormal renal function 1 Abnormal liver function 1 Stroke in past 1 Bleeding 1 Elderly 1 Labile INRs 1 Drugs NSAIDS, antiplatelets 1 ETOH 1

35. NON-PHARMACOLOGIC STROKE PREVENTION

36. Left Atrial Appendage (LAA) Occlusion By: WATCHMAN Device (Boston Scientific) Amplatzer cardiac plug (St. Jude) LAA Occlusion by using LARIAT (SentreHEART) device that ties off the LAA “epicardial snare” Requires subxiphoid pericardial approach Surgical excision of the LAA for pts undergoing cardiac surgery Yields inconsistent results

37. Masoudi FA, Calkins H, Kavinsky C; 2015 ACC/HRS/SCAI Left atrial Appendage Occlusion Device Societal Overview, JACC 2015;Jun 29

38. RATE CONTROL Resting rate < or = to 80, or average awake rate <100 Exercise rate should not exceed >100% of maximum predicted exercise rate

39. Rationale for Rate Control This is an important strategy as it Impacts QOL Reduces morbidity Decreases potential for developing tachycardia induced cardiomyopathy When selecting which agent(s) to use, must consider symptoms, hemodynamic status, presence of HF Beta blockers, non-dihydropyridine CCB’s, digoxin, amiodarone, sotalol are the main considerations When rapid control of ventricular rate during AF required, IV meds or electrical CV may be used. May increase TE risk in those inadequately anticoagulated

41. AV Node Ablation as Rate Control Strategy Permanent Pacemaker implantation with subsequent AV node ablation effectively controls and regularizes ventricular heart rate and in select patients, improves symptoms Those most likely to benefit are those with symptomatic AF with RVR that is either non responsive to medications or the pt is intolerant to the meds Usually reserved for the elderly, as it makes one pacemaker dependent Rate control meds no longer needed, but still require anticoagulation

42. RHYTHM CONTROL

43. Rationale for Rhythm Control This is a chance for shared decision making with the pt. Always treat precipitating or reversible causes first All rhythm control options should be considered only under optimal TE prevention strategies. If symptoms not controlled with rate regulation, or pt less than 65 yrs old, it is reasonable to pursue restoration of NSR Choices include Pharmacologic, Ablation, Electrical Cardioversion alone or in combination Drugs that can convert: Amiodarone (IV/PO), Dofetilide (PO), Flecainide (PO), Propafenone (PO), Ibutilide (IV)

44. Drug Selection for Rhythm Control

47. AF Ablation Invasive procedure to isolate the atrial impulses causing AF and ablating those electrical pathways. Most common way is using radio frequency ablation, but cryo-ablation is now also being used. Associated with higher risk than antiarrhythmic drugs, but is generally more effective over the long term. Usually recommended for pts with symptomatic paroxysmal or persistent AF who are refractory or intolerant to at least 1 antiarrhythmic drug

48. Electrical Cardioversion Recommended for symptomatic AF with RVR that does not respond promptly to pharmacologic therapies and contributes to ongoing ischemia, hypotension or CHF Ideally, should be anticoagulated for 3 weeks prior, placed on an antiarrhythmic med, with a TEE to rule out intra- atrial clot, cardioversion then performed immediately following TEE. If clot is seen, CV is not performed. If AF is clearly less than 48 hours in duration, CV can be performed without TEE. Pt. should be anticoagulated ASAP. TE is most likely to occur within 72 hours after CV, can be as long as 10 days.

49. References Cairns JA, Connolly S, McMurtry S, Stephenson M, Talajic M; CCS Atrial Fibrillation Guidelines Committee. Canadian cardiovascular society atrial fibrillation guidelines 2010: prevention of stroke and systemic thromboembolism in atrial fibrillation and flutter. Can J Cardiol. 2011 Jan-Feb;27(1):74-90. Prystowsky EN, Padanilam BJ, Fogel, RI. Treatment of Atrial Fibrillation. JAMA. 2015;314(3):278-288. Moss JD, Cifu, AS. Management of Anticoagulation in Patients with Atrial Fibrillation. JAMA. 2015;314(3):291-292. Chugh, A, Masoudi FA, Calkins H, Davisnsky, C. 2015 ACC/HRS/SCAI Left Atrial Appendage Occlusion Device Societal Overview. JACC. 2015: June 29. January, CT, Wann, LS, et al. 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation. JACC. Vol 64, No 21. e1-79.