MANAGING ATRIAL FIBRILLATION: BEYOND ANTICOAGULATION December 9, 2017 1
Faculty Disclosure Faculty: Peter Leong-Sit MSc, MD, FRCPC, FHRS Associate Professor, Western University Cardiologist, London Heart Rhythm Program Relationships with commercial interests: Grants/Research Support: Bayer Consultant: St. Jude Medical, Medtronic, Johnson & Johnson Speaker s Bureau: Medtronic, Johnson & Johnson, St. Jude Medical, Bayer, Boehringer Ingelheim, Pfizer, Boston Scientific Potential for conflict(s) of interest: Bayer, St. Jude Medical, Medtronic, Johnson & Johnson, Boehringer Ingelheim, Pfizer, Boston Scientific develop and benefit from the sale of products that might be discussed in this program. 2
Mitigating Potential Bias All the recommendations involving clinical medicine are based on evidence that is accepted within the profession. All scientific research referred to, reported, or used is in the support or justification of patient care. Recommendations conform to the generally accepted standards. The presentation will mitigate potential bias by ensuring that data and recommendations are presented in a fair and balanced way. Potential bias will be mitigated by presenting a full range of products that can be used in this therapeutic area. 3
Learning Objectives 1. To review management strategies for atrial fibrillation 2. To identify good candidates for rhythm control or ablation for atrial fibrillation 3. To provide an overview of atrial fibrillation ablation principles 4. To provide an overview of invasive options for stroke prevention 4
Case #1: 66F with prior MI, otherwise healthy Cath: preserved LVEF, non-surgical coronary disease No further CP since MI 3 years ago Frequent daily palpitations Meds: ASA, ramipril 5mg, bisoprolol 5mg, atorvastatin 40mg 5
Is this Atrial Fibrillation? a) Yes b) No 6
Holter: Is this Atrial Fibrillation? a) Yes b) No 7
Is this Atrial Fibrillation? a) Yes b) No 8
Is this Atrial Fibrillation? a) Yes b) No 9
24-Hour Holter Monitor Predominant rhythm sinus Salvos of AF lasting 15 seconds to 45 minutes correlating with mild palpitations No conduction disease, AV block Mean rate = 80bpm [50-130bpm] Rates in AF = 90-120bpm 10
Outpatient AF Management AF Management Precipitating cause Stroke Symptoms ASA Warfarin Dabigatran Rivaroxaban Apixaban (LAA Occlusion) Rate Control vs Rhythm Control Medical vs Ablation 11
Back to our Case... 66F with paroxysmal AF Prior MI, preserved LVEF, no CHF Otherwise healthy Would you recommend: a) Nothing b) ASA c) Warfarin d) NOAC 12
CHADS 2 Score Combination of AFI and SPAF schemes 1 Congestive Heart Failure 1 Hypertension 1 Age > 75 years 1 Diabetes Mellitus 2 Stroke or TIA Score* Stroke rate 0 1.9 (1.2-3.0) 1 2.8 (2.0-3.8) 2 4.0 (3.1-5.1) 3 5.9 (4.6-7.3) 4 8.5 (6.3-11.1) 5 12.5 (8.2-17.5) 6 18.2 (10.5-17.4) *Score 0: Patients can be administered aspirin *Score 1: Patients can be on aspirin or systemic anticoagulation *Score 2: Patients should be on systemic anticoagulation Gage BF, et al. JAMA. 2001;285:2864-2870. 13
CHA 2 DS 2 VASc Score Score 0/9 = 0 thromboembolic events Score 1/9 = 0.6% (0.0 3.4%) Score 2/9 = 1.6% (0.3 4.7%) Lip GY et al. Chest. 2010 Feb;137(2):263-72. 14
Back to our Case... 66F with newly diagnosed AF No hypertension, diabetes, no prior CHF or stroke but prior MI Hence, CHADS 2 score = 0 But CHA 2 DS 2 -VASc score = 3! 15
2016 AF Guidelines CHADS-65 Macle L. et al. Can J Cardiol 2016;32:1170-85. 16
Back to our Case... 66F with newly diagnosed AF No hypertension, diabetes, no prior CHF or stroke but prior MI Hence, CHADS 2 score = 0 But CHA 2 DS 2 -VASc score = 3! Current Canadian guidelines: Over age 65, therefore anticoagulate 17
Summary of Approach Any patient above age 65 with AF should have systemic anticoagulation Below age 65 with CHADS2 risk factors should have systemic anticoagulation Below age 65 with vascular disease, ASA is recommended Below age 65 with no vascular disease, nothing is recommended 18
Which to Choose? Is warfarin ok for my patient? Mechanical valve. definitely warfarin Excellent INRs (TTR > 70%) may limit benefits of switching Renal Function / Liver Metabolism Poor renal function (GFR < 30-50) Apixaban, rivaroxaban > dabigatran GFR < 15... definitely warfarin Compliance of Once daily vs Twice daily No monitoring of compliance 19
2014/2016 Canadian AF Guidelines Emphasis is on choosing the new agents over warfarin rather than choosing between the new agents Warfarin based on RCT data < 6600 pts New agents tested in > 70,000 pts Verma et al. Can J Cardiol 2014;30:1114-30. Macle et al. Can J Cardiol 2016;32:1170-85. 20
Limited Use Coverage Clinical Criteria 1) Failed warfarin trial > 2 months > 35% INRs outside therapeutic range 2) Warfarin contraindicated or inability to monitor INRs 21
Limited Use Codes Dabigatran = 431 Rivaroxaban = 435 Apixaban = 448 Edoxaban =?coming soon 22
WHAT ABOUT BLEEDING RISK?
Patient Preferences Lahaye S et al. Thromb Haemost. 2013 Dec 12;111(4) 24
Mortality rate (%) Mortality after major bleed: 5 Phase III trials 0.2 0.1 0 0.3 Warfarin Dabigatran 5 10 15 20 25 30 35 Time (days) The Kaplan Meier analysis indicated a reduced risk for death with dabigatran* vs warfarin during 30 days from the bleeding (P=0.052) Majeed A. et al. Management and Outcomes of Major Bleeding on Dabigatran or Warfarin, American Society of Hematology Conference, Atlanta, GA, Dec 2012 25 25
Remember: There is Harm in Inaction Single antiplatelet agent Dual antiplatelet therapy 25% 3% 15% No antithrombotics Warfarin subtherapeutic 39% 18% Warfarin therapeutic 82% of AF patients with a 2 nd stroke were not anticoagulated Gladstone DJ, et al. Stroke 2009;40:235-240
Case #2: 82F with persistent AF Problem List: Hypertension, Diabetes, Dylipidemia Post-partum DVT with a PE L. breast Ca with mastectomy 2010 CHADS = 3, CHADS-VASc score = 4 On warfarin, suffered large GI bleed 27
What is the next step? a) Continue warfarin b) Stop warfarin, start ASA c) Stop warfarin, start NOAC d) Stop warfarin, refer for LA appendage closure 28
Case #2 Endoscopy: reactive gastropathy and vascular ectasias Switched to Rivaroxaban 20mg daily, recurrent GI bleed Switched to Apixaban 2.5mg bid, recurrent GI bleed 29
Mechanism of Stroke in AF Slow-moving blood that pools can form clot in the LAA, which can embolize and result in Stroke 30
Approved Percutaneous Options Amplatzer Cardiac Plug (SJM) Watchman device (BSx) 31
The Watchman Left Atrial Appendage Closure Device Maisel W. N Engl J Med 2009 During Endothelialization: Warfarin for 45 days ASA / Plavix for 6 months (TEE) ASA alone
Meta-Analysis Shows Comparable Primary Efficacy Results to Warfarin HR p-value Efficacy 0.79 0.22 All stroke or SE 1.02 0.94 Ischemic stroke or SE 1.95 0.05 Hemorrhagic stroke 0.22 0.004 Ischemic stroke or SE >7 days 1.56 0.21 CV/unexplained death 0.48 0.006 All-cause death 0.73 0.07 Major bleed, all 1.00 0.98 Major bleeding, non procedure-related 0.51 0.002 Favors WATCHMAN Favors warfarin 0.01 0.1 1 10 Hazard Ratio (95% CI) Source: Holmes DR, et al. Holmes, DR et al. JACC 2015; In Press. Combined data set of all PROTECT AF and PREVAIL WATCHMAN patients versus chronic warfarin patients 33
Who should be considered for LAA Closure? 1. Major bleeding while taking anticoagulation therapy 2. Inability to maintain stable INR and not a NOAC candidate 3. CVA/TIA despite therapeutic warfarin or NOAC 34
AF Stroke Prevention Key Points Remember CHADS65 risk score NOACs preferred over warfarin NOACs contraindicated in mechanical valves and severe renal failure LAA closure not a replacement for OAC, but can be considered in refractory cases 35
Outpatient AF Management AF Management Precipitating cause Stroke Symptoms ASA Warfarin Dabigatran Rivaroxaban Apixaban (LAA Occlusion) Rate Control vs Rhythm Control Medical vs Ablation 36
HOW DO I DECIDE BETWEEN RATE VS RHYTHM CONTROL?
Case #3: 57M with Lone Paroxsymal AF Severe palpitations 1-3x/month, up to 45 minutes Problem List: mild asthma, solitary kidney with Cr 150 AF with HR = 110bpm 38
How should the AF be treated? a) Metoprolol 25mg BID b) Diltiazem 120mg daily c) Digoxin 0.125mg daily d) Amiodarone 200mg daily 39
AFib Medical Options 101 Review AVN blocking agents SLOW the AF Beta-receptor antagonist Ca-channel blockers Digoxin Anti-arrhythmic agents STOP the AF Class I: Propafenone, Flecainide Class III: Sotalol, Dronedarone, Amiodarone 40
AFFIRM (Rate vs Rhythm) Primary endpoint: All cause mortality N=4,060 No difference between two groups Trend to better survival for rate control after 1.5-2 yrs Secondary endpoints functional status QOL ischemic strokes No difference AFFIRM Investigators NEJM 2002;347:1825 41
Back to Case Young patient with lone PAF Key issue is symptom control Symptoms during AF are poorly rate-controlled (110bpm) Always start with an AVN blocking agent 42
Follow-up Visit Patient now on diltiazem 360 mg bid Sinus rates now 50 bpm Repeat Holter: AF episodes still recurrent, but associated with heart rate of 70-90 bpm 43
What is the next step? a) The AF is well rate-controlled... Continue current management b) The AF is still recurrent... Add digoxin c) The AF is still recurrent... Change to an antiarrhythmic medication d) I don t know 44
Outpatient AF Management AF Management Precipitating cause Stroke Symptoms ASA Warfarin Dabigatran Rivaroxaban Apixaban (LAA Occlusion) Rate Control vs Rhythm Control Medical vs Ablation 45
I TRIED AVN AGENTS AND THE PATIENT STILL FEELS AWFUL. NOW WHAT?
Why Rhythm Control? No Symptoms Symptoms Primary evidence-based efficacy is improvement in symptoms Rhythm control should NOT be performed to: Reduce stroke risk Discontinue systemic anticoagulants Make the ECG or Holter look better 47
Back to Case... Patient is referred to cardiology / EP specialist They are started on an antiarrhythmic medication What do I need to know? 48
Anti-arrhythmic Drug Options Four predominant anti-arrhythmics for rhythm control of AF 1. Propafenone 2. Flecainide (Class I AADs) 3. Sotalol 4. Amiodarone (Class III AADs) 49
Anti-arrhythmic Basics Flecainide/Propafenone Requires adjunct AVN blocking agent Contraindicated in heart disease Can widen the QRS or cause VT Typical doses: Flecainide 50mg bid - 150mg bid Propafenone 75mg bid/tid - 300mg tid 50
Anti-arrhythmic Basics Sotalol Already has AVN blocking properties Can be used as single agent Dosing 80mg bid - 160mg bid Risk of Torsades de Pointes Contraindicated in Long QT or renal failure Cautious with elderly, females Repeat ECG in 1 wk for QT prolongation 51
Anti-arrhythmic Basics Amiodarone Already has AVN blocking properties Can be used as single agent Loading dose: 10g load (400mg bid/tid) Maintenance dose: 200mg daily Requires monitoring for side effects TSH, liver tests every 6 months CXR every year, baseline PFT Ophthalmology, CT chest if symptoms 52
Pill-In-The-Pocket Approach Flecainide 200-300mg x 1 PRN Propafenone 450-600mg x 1 PRN 53
AAD Strategy Depends on episode frequency & duration Rare Infrequent Weekly Days Hours Minutes Pill-In-Pocket Maintenance 54
Back to Case... Sotalol was started and up-titrated Symptoms continued Patient was switched to Amiodarone and is feeling better Is he going to be considered for cardiac ablation? 55
AF Invasive Options Invasive Rate Control AV node ablation (99% success) (with pacemaker implantation) Invasive Rhythm Control Atrial flutter ablation (95% success) Atrial fibrillation ablation (50-80% success) 56
AV Node Ablation and Pacemaker Causes complete AV block Atria continue to fibrillate Pacemaker controls HR Must remain on anticoagulation Ultimate rate-control strategy 99% success 1% risk
What about invasive rhythm control? Contrast Aflutter and Afib Easier to rhythm control Harder to rate control Simple ablation 95% success Low risk 1-2% Difficult to rhythm control Easier to rate control Complex ablation 50-80% success Higher risk 3-4% 58
Atrial Flutter Counterclockwise right atrial reentry
Atrial Flutter Ablation Ablation of the cavo-tricuspid isthmus (CTI) Predictable circuit Small lesion set First-line therapy
AFib Electrophysiology Chaotic disorganized rhythm
Pulmonary Vein Ectopy
Fencing off all 4 Veins Success rates for paroxysmal AF is 70-80% Still requires anticoagulation
First-line Rhythm Control? Which patients should I refer early? ** Atrial flutter Kerr C, Roy D. Can J Cardiol 2004. 64
Stroke Take-Home Points Use CHADS65 risk stratification NOAC preferred over warfarin For those who have a true anticoagulation contraindication, consider LAA closure 65
Symptom Take-Home Points For symptomatic atrial fibrillation, start with rate control for most Refer if still symptomatic for initiation of anti-arrhythmic medications or catheter ablation Rhythm control has little role for minimally symptomatic patients Rhythm control does not reduce stroke risk 66
Questions? 67