Prepared by Pfizer-BMS alliance in response to an unsolicited request Not for further distribution

AF review Petr Polasek

Copyright 2017 by Sea Courses Inc. All rights reserved. No part of this document may be reproduced, copied, stored, or transmitted in any form or by any means graphic, electronic, or mechanical, including photocopying, recording, or information storage and retrieval systems without prior written permission of Sea Courses Inc. except where permitted by law. Sea Courses is not responsible for any speaker or participant s statements, materials, acts or omissions.

Atrial Fibrillation: 4 Principles 1. PREVENT Stroke/Embolization 2. Render patient ASYMPTOMATIC/ functional 3. Investigate ETIOLOGY 4. Consider benefit/risk ratio of SINUS restoration

A quiz World is getting Younger Older Older world equals Less Strokes More Strokes

We are in trouble! More than 37 million people are age 65. By 2030, this number will exceed 70 million. By 2040, those aged 75 years will exceed the population 65 to 74 years old. By 2050, 12%, or 1 in 8 Americans, will be age 75 or older.

Prevalence, percent AF Prevalence: Age and Gender Prevalence of atrial fibrillation with age JAMA 2001; 285: 2370 Age, years

Prepared by Pfizer-BMS alliance in response to an unsolicited request Not for further distribution

Atrial Fibrillation: 4 Principles 1. PREVENT Stroke/Embolization 2. Render patient ASYMPTOMATIC/ functional 3. Investigate ETIOLOGY 4. Consider benefit/risk ratio of SINUS restoration

Note to self: CVA prevention is the MOST important issue

CHADS 2 Score (Simple Prediction Tool for Assessing Stroke Risk) CHADS 2 Score* Stroke Rate, %/yr (95 %CI) 0 1.9 (1.2 3.0) 1 point for Congestive Heart Failure 1 point for Hypertension 1 point for Age 75 years 1 point for Diabetes Mellitus 2 points for Prior Stroke or TIA 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 27.4) *Score 0: Patients can be administered aspirin *Score 1: Patients can be administered aspirin or anticoagulant therapy *Score 2: Patients should be administered anticoagulant therapy 1. Gage BF, et al. JAMA. 2001;285:2864-2870

CHA 2 DS 2 -VASc Score 1 point for Congestive Heart Failure/ LV Dysfunction 1 point for Hypertension 2 points for Age 75 years 1 point for Diabetes Mellitus 2 points for Prior Stroke or TIA 1 or TE 2 1 point for Vascular Disease 3 1 point for Age 65-74 years 1 point for Sex category (female gender) CHA 2 DS 2 -VASc Score* One year event rate (95% CI) of hospital admission and death due to thromboembolism per 100 person years 0 0.78 (0.78 1.04) 1 2.01 (1.70 2.36) 2 3.71 (3.36 4.09) 3 5.92 (5.53 6.34) 4 9.27 (8.71 9.86) 5 15.26 (14.35 16.24) 6 19.74 (18.21 21.41) 7 21.5 (18.75 24.64) 8 22.38 (16.29 30.76) 9 23.64 (10.62 52.61) *Score 0: Patients can be administered aspirin *Score 1: Patients can be administered aspirin or anticoagulant therapy *Score 2: Patients should be administered anticoagulant therapy Includes peripheral artery embolism, ischemic stroke, and pulmonary embolism 1 TIA = Transient ischemic attack; 2 TE = Thromboembolism 3 Prior myocardial infarction, peripheral artery disease, aortic plaque 1. Lip GY et al. Chest 2010;137:263-272 2. Olesen JB, et al. BMJ 2011;342:d124 3. Task Force or the Management of Atrial Fibrillation of the ESC. Eur Heart J 2010;31:236902429

HAS-BLED Bleeding Score (Simple Tool for Assessing Bleeding Risk) Letter Clinical Characteristic* Points Awarded: Score H Hypertension 1 A Abnormal renal or liver function (1 point each) 1 or 2 S Stroke 1 B Bleeding 1 L Labile INRs 1 E Elderly 1 D Drugs or alcohol (1 point each) 1 or 2 *Hypertension - uncontrolled, >160 mm Hg systolic; Abnormal renal/liver function (one point for presence of renal or liver impairment, maximum two points); Stroke (previous history, particularly lacunar); Bleeding history or predisposition (anemia); Labile international normalized ratio (INR) (i.e. therapeutic time in range < 60%); Elderly ( >65 years); Drugs/alcohol concomitantly (antiplatelet agents, nonsteroidal anti-inflammatory drugs; one point for drugs plus one point for alcohol excess, maximum two points). 1. Pisters R, et al. Chest 2010; 138(5):1093 1100

Prepared by Pfizer-BMS alliance in response to an unsolicited request Not for further distribution

Newly discovered AF WHAT to USE? ASA Warfarin NOAC's Which NOAC?

Prepared by Pfizer-BMS alliance in response to an unsolicited request Not for further distribution

Note to self: We are looking for a reason to anticoagulate

Food Interactions Green leafy vegetables counteract effects of warfarin Foods with high amounts of vitamin K, e.g: - Cauliflower - Green cabbage - Seaweed (1350) - Broccoli (270) - Green tea - Turnip greens - Soybean oil (often used to fry foods in restaurants) - Raw spinach 1. Ansell J, et al. Chest. June 2008 133:160S-198S.

Warfarin Has a Narrow Therapeutic Window Relationship between clinical events and INR intensity 1. Hylek EM et al. Ann Intern Med. 1994;120:897-902. 2. Hylek EM et al. N Engl J Med. 1996;335:540-546. ICH=intracranial hemorrhage INR=international normalized ratio

% of eligible patients receiving warfarin INR Control: Clinical Trial vs Clinical Practice (TTR) 70% 60% 50% 40% 30% 20% 10% 0% 25% 38% TTR = Time in Therapeutic Range (INR 2.0-3.0) 1. Kalra L, et al. BMJ 2000;320:1236-1239. 2. Matchar DB, et al. Am J Med 2002; 113:42-51 66% 44% Clinical trial Clinical practice 9% < 2.0 2.0-3.0 > 3.0 International Normalised Ratio (INR) 1 2 18%

Intensity of Anticoagulation with Warfarin and Stroke Rates 1. Hylek EM et al. N Engl J Med. 2003;349:1019-1026.

Note to self: Warfarin might not be the best drug

Prepared by Pfizer-BMS alliance in response to an unsolicited request Not for further distribution

Anti-Factor Xa activity (IU/mL) Direct comparison of the pharmacodynamics of apixaban and rivaroxaban Healthy volunteers (n=14) Crossover design 10.0 ANTI-XA APIXABAN 2.5MG BID RIVAROXABAN 10MG QD Peak (IU/mL) 1.12 2.82 Trough (IU/mL) 0.24 0.17 Ratio 4.7 16.5 Apixaban 2.5 mg BID 0.1 Rivaroxaban 10 mg QD 0 12 24 36 48 Time (h) Adapted from Frost et al. J Thromb Haemost [XXIII Congress of the ISTH, Kyoto, Japan, 2011] 2011;9 (Suppl 2): abstract no. P-WE-159. Prepared by Pfizer-BMS alliance in response to an unsolicited request Not for further distribution 30

Rivaroxaban plasma concentrations (μg/l) Food significantly affects the PK profile of rivaroxaban At the AF dose, rivaroxaban must be taken with food 2 In the ROCKET-AF study, rivaroxaban study drug had to be taken with the evening meal 3 FASTED FED* C max (ng/ml) 1 159.9 281.4 T max (h) 2 2.5 4 AUC (ng*h/ml) 1 1,477 2,048 350 300 250 200 150 100 39% higher AUC 76% higher Cmax Rivaroxaban 20 mg in 22 healthy volunteers After a single oral dose of 20mg rivaroxaban, AUC was increased by 39% and Cmax by 76% after administration with food 50 0 0 2 4 6 8 10 12 14 16 18 20 22 24 Time (hours) Fasted Fed 1. Stampfuss et al., Int J Clin Pharmacol Ther. 2013;51(7):549-61 2. Rivaroxaban PM, 2013 3. Protocol for: Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011;365:883-91. DOI: 10.1056/NEJMoa1009638. Prepared by Pfizer-BMS alliance in response to an unsolicited request Not for further distribution 31

Oral Anticoagulants: New Agents Warfarin (vitamin K antagonist) has traditionally been used as the anticoagulant of choice for stroke prevention. Recently, three new oral anticoagulants have been studied in clinical trials for stroke prevention in AF patients: AGENT CLASS APPROVAL STATUS IN CANADA FOR STROKE PREVENTION IN AF Dabigatran Direct thrombin inhibitor Approved Rivaroxaban Factor Xa inhibitor Approved Apixaban Factor Xa inhibitor Approved 1. Connoly SJ, et al. N Engl J Med 2009;361:1139-1151. 2. Patel MR, et al. N Engl J Med 2011;365:883-891. 3. Granger C, et al. N Engl J Med 2011;365:981-992

NOAC dosing recommendations in patients with renal impairment APIXABAN 1 RIVAROXABAN 2 DABIGATRAN 3 Mild - Moderate renal impairment (CrCl 30-50 ml/min) Yes Generally no dose reduction Dose adjustment only if 2 of ABC* criteria Yes 15mg QD Yes Dose reduction to be considered in elderly or those with other risk factors for bleeding Severe renal impairment (CrCl 25-29 ml/min) No Not recommended No Not recommended (CrCl 15-24 ml/min) no dosing recommendation can be made CrCl <15 ml/min or patients undergoing dialysis No Not recommended *ABC criteria: Dose reduction to 2.5 mg BID if at least 2 of the following: Age 80, Body weight 60kg, serum Creatinine 133micromol/L NOAC: novel oral anticoagulant CrCL: estimated creatinine clearance 1. Eliquis PM, 2012. 2. Rivaroxaban PM, 2013. 3. Dabigatran PM, 2013 Prepared by Pfizer-BMS alliance in response to an unsolicited request Not for further distribution 33

Event rate (%/yr) Novel Oral Anticoagulants Compared to Warfarin: Primary safety endpoint*, Major Bleeding Apixaban and dabigatran 110 significantly decrease major bleeding compared to warfarin Rivaroxaban and dabigatran 150 cause as much bleeding as warfarin ARISTOTLE 1 RE-LY 2 ROCKET-AF 3 p=0.58 3.5 3 p<0.001 3.5 3 p=0.003 p=0.31 3.5 3 2.5 2.5 2.5 2 1.5 1 3.09% 2.13% 2 1.5 1 3.36% 2.71% 3.11% 2 1.5 1 3.4% 3.6% 0.5 0.5 0.5 0 Warfarin Apixaban 0 Warfarin Dabi 110 Dabi 150 0 Warfarin Rivaroxaban HR 0.69 (95% CI: 0.60-0.80) Dabi 110 vs warfarin: HR: 0.80 (0.69 0.93) HR 1.04 (95% CI: 0.90-1.20) Dabi 150 vs warfarin: HR: 0.93 (0.81 1.07) No head-to-head trials between dabigatran, apixaban and rivaroxaban have been conducted, therefore comparative efficacy and safety have not been established. * The primary safety endpoint in ROCKET-AF was major bleeding + CRNM; major bleeding was a secondary safety endpoint 1. Granger et al., NEJM 2011; 365: 981-992 2. Connolly et al., NEJM 2009; 361: 1139-1151 3. Patel et al., NEJM 2011; 365: 883-891 Prepared by Pfizer-BMS alliance in response to an unsolicited request Not for further distribution 34

Novel Oral Anticoagulants Compared to Warfarin: Primary safety endpoint*, Major Bleeding Apixaban and dabigatran 110 significantly decrease major bleeding compared to warfarin Rivaroxaban and dabigatran 150 cause as much bleeding as warfarin Hazard Ratio Apixaban 1 HR 0.69 (95%CI, 0.60-0.80); p<0.001 Dabigatran 150 mg 2 HR 0.93 (95%CI, 0.81-1.07); p=0.31 Dabigatran 110 mg 2 HR 0.80 (95%CI, 0.69-0.93); p=0.003 Rivaroxaban 3 HR 1.04 (95%CI, 0.90-1.20); p=0.58* 0.5 1.0 1.5 Study Drug Better Warfarin Better No head-to-head trials between dabigatran, apixaban and rivaroxaban have been conducted, therefore comparative efficacy and safety have not been established. * The primary safety endpoint in ROCKET-AF was major bleeding + CRNM; major bleeding was a secondary safety endpoint 1. Granger et al., NEJM 2011; 365: 981-992 2. Connolly et al., NEJM 2009; 361: 1139-1151 3. Patel et al., NEJM 2011; 365: 883-891 Prepared by Pfizer-BMS alliance in response to an unsolicited request Not for further distribution 35

Event rate (%/yr) Novel Oral Anticoagulants Compared to Warfarin: Intracranial Hemorrhage (ICH) Apixaban, dabigatran and rivaroxaban significantly decrease intracranial bleeding compared to warfarin 1 ARISTOTLE 1 1 RE-LY 2 1 ROCKET-AF 3 0.8 p<0.001 0.8 0.8 0.6 0.6 0.6 p=0.02 0.4 0.2 0.80% 0.33% 0.4 0.2 0.74% p<0.001 0.23% 0.4 p<0.001 0.7% 0.30% 0.2 0.5% 0 Warfarin Apixaban 0 Warfarin Dabi 110 Dabi 150 0 Warfarin Rivaroxaban HR 0.42 (95% CI: 0.30-0.58) Dabi 110 vs warfarin: HR: 0.31 (0.20 0.47) HR 0.67 (95% CI: 0.47-0.93) Dabi 150 vs warfarin: HR: 0.40 (0.27 0.60) No head-to-head trials between dabigatran, apixaban and rivaroxaban have been conducted, therefore comparative efficacy and safety have not been established. 1. Granger et al., NEJM 2011; 365: 981-992 2. Connolly et al., NEJM 2009; 361: 1139-1151 3. Patel et al., NEJM 2011; 365: 883-891 Prepared by Pfizer-BMS alliance in response to an unsolicited request Not for further distribution 36

Novel Oral Anticoagulants Compared to Warfarin: Intracranial Hemorrhage (ICH) Apixaban, dabigatran and rivaroxaban significantly decrease intracranial bleeding compared to warfarin Hazard Ratio Apixaban 1 HR 0.42 (95%CI, 0.30-0.58); p<0.001 Dabigatran 150 mg 2 HR 0.40 (95%CI, 0.27-0.60); p<0.001 Dabigatran 110 mg 2 HR 0.31 (95%CI, 0.20-0.47); p<0.001 Rivaroxaban 3 HR 0.67(95%CI, 0.47-0.93); p=0.02 0 0.5 1.0 1.5 2.0 Study Drug Better Warfarin Better No head-to-head trials between dabigatran, apixaban and rivaroxaban have been conducted, therefore comparative efficacy and safety have not been established. 1. Granger et al., NEJM 2011; 365: 981-992 2. Connolly et al., NEJM 2009; 361: 1139-1151 3. Patel et al., NEJM 2011; 365: 883-891 Prepared by Pfizer-BMS alliance in response to an unsolicited request Not for further distribution 37

Event rate (%/yr) Novel Oral Anticoagulants Compared to Warfarin: GI bleeding Rivaroxaban and dabigatran 150 increase GI bleeding compared to warfarin Apixaban and dabigatran 110 cause as much GI bleeding as warfarin 3 ARISTOTLE 1 3 RE-LY 2 3 ROCKET-AF 3,4,5 2.5 2.5 2.5 2 2 2 p<0.001 1.5 1.5 p=0.43 p<0.001 1.5 1 0.5 p=0.37 0.86% 0.76% 1 0.5 1.02% 1.12% 1.51% 1 0.5 1.24% 2% 0 Warfarin Apixaban 0 Warfarin Dabi 110 Dabi 150 0 Warfarin Rivaroxaban HR 0.89 (95% CI: 0.70-1.15) Dabi 110 vs warfarin: HR: 1.10 (0.86 1.41) HR 1.61 (95% CI:1.30-1.99) Dabi 150 vs warfarin: HR: 1.5 (1.19 1.89) No head-to-head trials between dabigatran, apixaban and rivaroxaban have been conducted, therefore comparative efficacy and safety have not been established. 1. Granger et al., NEJM 2011; 365: 981-992 2. Connolly et al., NEJM 2009; 361: 1139-1151 3. Patel et al., NEJM 2011; 365: 883-891 4. Desai et al., Gastrointest Endosc 2013; 78: 227-239 5. Nessel et al., Chest J 2012; 142: 84A Prepared by Pfizer-BMS alliance in response to an unsolicited request Not for further distribution 38

Novel Oral Anticoagulants Compared to Warfarin: GI bleeding Rivaroxaban and dabigatran 150 increase GI bleeding compared to warfarin Apixaban and dabigatran 110 cause as much GI bleeding as warfarin Hazard Ratio Apixaban 1 HR 0.89 (95%CI, 0.70-1.15); p=0.37 Dabigatran 110 mg 2 HR 1.10 (95%CI, 0.86-1.41); p=0.43 Dabigatran 150 mg 2 HR 1.50 (95%CI, 1.19-1.89); p<0.001 Rivaroxaban 3,4,5 HR 1.61 (95%CI, 1.30-1.99); p<0.001 0 0.5 1.0 1.5 2.0 Study Drug Better 1. Granger et al., NEJM 2011; 365: 981-992 2. Connolly et al., NEJM 2009; 361: 1139-1151 3. Patel et al., NEJM 2011; 365: 883-891 4. Desai et al., Gastrointest Endosc 2013; 78: 227-239 5. Nessel et al., Chest J 2012; 142: 84A Prepared by Pfizer-BMS alliance in response to an unsolicited request Not for further distribution Warfarin Better No head-to-head trials between dabigatran, apixaban and rivaroxaban have been conducted, therefore comparative efficacy and safety have not been established.

Event rate (%/yr) Apixaban Bleeding endpoints as compared to Aspirin Apixaban is the only NOAC tested against ASA in a blinded randomised trial, the AVERROES clinical trial Apixaban is superior to ASA in the reduction of stroke or systemic embolism Apixaban did not significantly increase major, ICH nor GI bleeding, when compared to ASA 2 MAJOR BLEEDING 2 ICH 2 GI 1.6 p=0.57 1.6 1.6 1.2 1.2 1.2 0.8 0.4 1.2% 1.4% 0.8 0.4 p=0.69 0.8 0.4 p=0.71 0.4% 0.4% 0.4% 0.4% 0 ASA Apixaban 0 ASA Apixaban 0 ASA Apixaban HR 1.13 (95% CI: 0.74-1.75) HR 0.85 (95% CI: 0.38-1.9) HR 0.86 (95% CI: 0.40-1.86) NOAC: novel oral anticoagulant Bleeding endpoints in the AVERROES study are calculated on the ITT population, as prespecified Adapted from Connolly et al. N Engl J Med 2011;364:806-17. Prepared by Pfizer-BMS alliance in response to an unsolicited request Not for further distribution 40

Event rate (%/yr) Novel Oral Anticoagulants Compared to Warfarin: All cause death Apixaban significantly decreases all cause death as compared to warfarin Dabigatran and rivaroxaban have no significant effect on mortality, as compared to warfarin ARISTOTLE RE-LY ROCKET-AF 5 5 5 p=0.15 4 p=0.047 4 p=0.13 p=0.051 4 3 3 3 2 3.94% 3.52% 2 4.13% 3.75% 3.64% 2 4.9% 4.5% 1 1 1 0 Warfarin Apixaban 0 Warfarin Dabi 110 Dabi 150 0 Warfarin Rivaroxaban HR 0.89 (95% CI: 0.80-0.998) Dabi 110 vs warfarin: HR: 0.91 (0.80 1.03) HR 0.92 (95% CI: 0.82-1.03) Dabi 150 vs warfarin: HR: 0.88 (0.77 1.00) No head-to-head trials between dabigatran, apixaban and rivaroxaban have been conducted, therefore comparative efficacy and safety have not been established. Adapted from Granger et al. N Engl J Med 2011;365:981-92 Adapted from Connolly SC et al. N Engl J Med 2009;361:1139 1151 Adapted from Patel MR, et al. N Engl J Med. 2011 Sep 8;365(10):883-91. Prepared by Pfizer-BMS alliance in response to an unsolicited request Not for further distribution 41

New Anticoagulant Therapies Compared to Warfarin: All-Cause Mortality Apixaban significantly decreases all cause death as compared to warfarin Dabigatran and rivaroxaban have no significant effect on mortality, as compared to warfarin Hazard Ratio Apixaban 1 HR 0.89 (95% CI, 0.80 to 0.998) Dabigatran 150 mg 2 HR 0.88 (95% CI, 0.77 to 1.00) Dabigatran 110 mg 2 HR 0.91 (95% CI, 0.80 to 1.03) Rivaroxaban 3 HR 0.92 (95% CI, 0.82 to 1.03) 0.75 0.80 0.90 1.0 1.10 1.20 1.25 Study Drug Better Warfarin Better No head-to-head trials between dabigatran, apixaban and rivaroxaban have been conducted, therefore comparative efficacy and safety have not been established. 1. Granger et al., NEJM 2011; 365: 981-992 2. Connolly et al., NEJM 2009; 361: 1139-1151 3. Patel et al., NEJM 2011; 365: 883-891 Prepared by Pfizer-BMS alliance in response to an unsolicited request Not for further distribution 42

Novel Oral Anticoagulants as Compared to Warfarin APIXABAN 1 VS. WARFARIN DABIGATRAN 110 2 VS. WARFARIN DABIGATRAN 150 2 VS. WARFARIN RIVAROXABAN 3 VS. WARFARIN RR (95% CI) P RR (95% CI) P RR (95% CI) P RR (95% CI) P Stroke/SE 0.79 (0.66 0.95) = 0.01 0.91 (0.74 1.11) 0.34 0.66 (0.53 0.82) < 0.001 0.88 (0.75 1.03) 0.12 Major Bleed 0.69 (0.60 0.80) < 0.001 0.80 (0.69 0.93) 0.003 0.93 (0.81 1.07) 0.31 1.04 (0.90 1.20) 0.58 Intra Cranial Bleed 0.42 (0.30 0.58) < 0.001 0.31 (0.20 0.47) < 0.001 0.40 (0.27 0.60) < 0.001 0.67 (0.47 0.93) 0.02 GI bleeding 0.89 (0.70-1.15) 0.37 1.10 (0.86-1.41) 0.43 1.5 (1.19-1.89) <0.001 1.61 (1.30-1.99) <0.001 All cause Death 0.89 (0.80 0.99) 0.047 0.91 (0.80 1.03) 0.13 0.88 (0.77 1.00) 0.051 0.92 (0.82 1.03) 0.15 No head-to-head trials between dabigatran, apixaban and rivaroxaban have been conducted, therefore comparative efficacy and safety have not been established. 1. Granger et al., NEJM 2011; 365: 981-992 2. Connolly et al., NEJM 2009; 361: 1139-1151 3. Patel et al., NEJM 2011; 365: 883-891 Prepared by Pfizer-BMS alliance in response to an unsolicited request Not for further distribution 43

Novel Oral Anticoagulants as Compared to Warfarin APIXABAN 1 DABIGATRAN 110 2 DABIGATRAN 150 2 RIVAROXABAN 3 VS. WARFARIN Stroke/SE Major Bleed Intra Cranial Bleed GI bleeding All cause Death = = = = = = = = = No head-to-head trials between dabigatran, apixaban and rivaroxaban have been conducted, therefore comparative efficacy and safety have not been established. 1. Granger et al., NEJM 2011; 365: 981-992 2. Connolly et al., NEJM 2009; 361: 1139-1151 3. Patel et al., NEJM 2011; 365: 883-891 Prepared by Pfizer-BMS alliance in response to an unsolicited request Not for further distribution 44

Real Life Data All drugs safer than Warfarin Rivoraxaban INR testing controversy 45

Note to self: NOAC is a safer choice

Newly discovered AF Symptom relief Strict vs. lenient Younger patients tolerate HR poorly Younger need better rate control, 2+ meds If slow w/o meds: high chance of pacemaker Rx: Beta Blockers, Calcium Blockers, Digoxin, Amiodarone

Prepared by Pfizer-BMS alliance in response to an unsolicited request Not for further distribution

Note to self: Not every new AF needs ER or CARDIOVERSION

Newly discovered AF Etiology/testing: Paroxysmal/Permanent CVA risk difference? AFib or AFlutter - CVA risk/management difference? Common: Age, Resp (COPD, OSA, p/e, PuHTN, lobectomy, pneumonia), LVH producers (HTN, Valve, CoArct), Noncardiac (Hg, Thyroid, Rx, Infection)

Newly discovered AF - SR restoration? Consider in : young (<65), very symptomatic ER visit is not an indication Chemical (Sotalol-Propafenone- Amiodarone)/Electrical/Mechanical EP AF ablation: 80-90%, better chance of SR with low CHADS

Note to self: Sinus rhythm is not a necessity

Atrial Fibrillation: 4 Principles 1. PREVENT Stroke/Embolization 2. Render patient ASYMPTOMATIC/ functional 3. Investigate ETIOLOGY 4. Consider benefit/risk ratio of SINUS restoration