Primary Care Update in Medicine January 31 February 1, 2013 New Management Options for Patients with Atrial Fibrillation

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1 Primary Care Update in Medicine January 31 February 1, 2013 New Management Options for Patients with Atrial Fibrillation Anne B. Curtis, MD, FACC, FHRS, FACP, FAHA Charles and Mary Bauer Professor, Chair, University at Buffalo Department of Medicine CEO and President, UB MD Internal Medicine

2 Disclosures Advisory Board Sanofi Aventis St. Jude Medical Biosense Webster Janssen Pharmaceuticals Bristol Myers Squibb Honoraria Medtronic, Inc. St. Jude Medical Sponsored Research Medtronic, Inc.

3 A 69 year old Caucasian female is referred from her primary care physician s office after she presented with episodic palpitations and was found to have new onset atrial fibrillation. She has a past medical history of hypertension that is well controlled with lisinopril 10 mg daily. There is no history of diabetes mellitus, prior stroke or transient ischemic attack, or cardiovascular disease. What are her CHADS 2 and the CHA 2 DS 2 -VASc scores? a) 1 and 1 b) 1 and 2 c) 1 and 3 d) 1 and 4 Pre-Test Question #1.

4 Pre-Test Question #2. What anti-thrombotic therapy would you initiate to prevent a risk of stroke in this patient? a) None, her risk for stroke is low b) Aspirin 325 mg daily c) Aspirin 325 mg + clopidogrel 75 mg daily d) Warfarin to maintain a therapeutic INR between 2 and 3

5 Pre-Test Question #3. A 73 year old patient is referred for preoperative evaluation for knee replacement surgery because her ECG showed previously undiagnosed atrial fibrillation. She denies cardiovascular symptoms, but she has treated hypertension and a history of myocardial infarction. There is no history of diabetes mellitus, stroke or TIA, or bleeding problems. She denies illicit drug or alcohol use. Her weight is 92.7 kg, Her serum creatinine is 3.2 mg/dl and estimated creatinine clearance is 14 ml/min; liver function is normal. The ECG shows AF with an average ventricular rate of 75 bpm. Echocardiogram shows left ventricular hypertrophy and left atrial enlargement.

6 Which anticoagulation strategy would you recommend? a) Aspirin b) Warfarin c) Dabigatran d) Rivaroxaban

7 Projected Number of Persons With AF (millions) AF Prevalence Is Rapidly Increasing Miyasaka et al. Circulation. 2006;114: Year Current age-adjusted AF incidence Increased age-adjusted AF incidence

8 The Consequences of AF Thromboembolism Stroke: 4.5 increased risk Microemboli: reduced cognitive function Prothrombotic state Hospitalizations Most common arrhythmia requiring hospitalization 2-3 increased risk for hospitalization Reduced QoL Palpitations, dyspnea, fatigue, reduced exercise tolerance Mortality 2 increased risk independent of comorbid CV disease Sudden death in HF and HCM Impaired Hemodynamics Loss of atrial kick Irregular ventricular contractions HF Tachycardia-induced cardiomyopathy HCM=hypertrophic cardiomyopathy. Van Gelder et al. Europace. 2006;8: ; Narayan et al. Lancet. 1997;350: ; Wattigney et al. Circulation. 2003;108: ; Wyse et al. Circulation. 2004;109: ; Favale et al. PACE. 2003;26:

9 What Happens When AF Persists? Structural Remodeling LA and LAA dilatation Fibrosis Electro- physiologic Remodeling Decrease in Ca++ currents Shortening of atrial action potential Increased importance of early activating K + channels: I Kur, I Kto Remodeling explains why AF begets AF

10 Patients in SR (%) Greater SR Maintenance With Earlier Cardioversion AF Duration prior to cardioversion <3 months 3-12 months >12 months 40 a Month 6 Months a P<.02. Dittrich et al. Am J Cardiol. 1989;63: (B).

11 Prevention of Stroke

12 Modification of Stroke Risk CHADS 2 Stratification in AF CHA 2 DS 2 -VASc Risk Factor Score Cardiac failure 1 HTN 1 Age 75 y 1 Diabetes 1 Stroke 2 Total Score Annual Risk of Stroke (%) CHADS 2 CHA 2 DS 2 -VASc Risk Factor Score Cardiac failure 1 HTN 1 Age 75 y 2 Diabetes 1 Stroke 2 Vasc dz (MI, PAD, aortic ath) 1 Age y 1 Sex category (female) 1 CHADS2 Score CHA 2 DS 2 -VASc Risk Intermediate High % 21.7% % Lip GY, Halperin JL. Am J Med 2010;123(6): Olesen JB, et al. Br Med J 2011;342:d124.

13 HAS-BLED Bleeding Risk Score* Letter H A S B L E D Clinical Characteristic HTN Abnormal renal and liver function (1 point each) Stroke Bleeding Labile INRs Elderly (age >65 years) Drugs or alcohol (1 point each) Score 1 1 or or 2 Maximum 9 points Risk Factors/ Score N Number of Bleeds Bleeds per 100 Patient-Years Any Score P-Value for Trend.007 *HAS-BLED study has not yet been validated in other data sets; Score of 3 indicates high risk, and some caution and regular patient review is needed following initiation of antithrombotic therapy. INRs = international normalized ratios. Camm AJ, et al. Eur Heart J. 2010;31(19): Pisters R. Chest. 2010;138: Lip GY, et al. Am J Med. 2010;123(6):

14 Outcome/Year (%) Outcome/Year (%) Antiplatelet Therapy in AF 6 ACTIVE-W: 6706 randomized patients; trial stopped P =.0003 Clopidogrel + ASA Warfarin ACTIVE-A: 7554 randomized patients; median follow-up of 3.6 years P =.01 Clopidogrel + ASA ASA P< P =.001 P = P< Vascular Event Stroke Major Bleeding 0 Vascular Event Stroke Major Bleeding ACTIVE = AF Clopidogrel Trial with Irbesartan for Prevention of Vascular Events. ACTIVE Investigators. Lancet. 2006;367: ACTIVE Investigators. N Engl J Med. 2009;360(20):

15 Newer Anticoagulants Warfarin, dabigatran, and rivaroxaban are FDA approved at the present time. Activated Factor X Inhibitors Apixaban Betrixaban Edoxaban (DU-176b) TAK-442 Rivaroxaban YMI 50 Direct Thrombin Inhibitors Dabigatran Etexilate AZD0837 MCC977 Warfarin Novel Vitamin K Antagonist ATI-5923 Extrinsic Pathway Activation Intrinsic Pathway Activation Factor X Activated Factor X Inhibitors Prothrombin Direct Thrombin Inhibitors Factor Xa Fibrinogen Thrombin Factor X Fibrin Ma TKW, et al. Pharmacology and Therapeutic 2010; doi; /j.pharmthera

16 Dabigatran Etexilate: Pharmacokinetics Pro-drug converted to dabigatran via hepatic microsomal carboxylesterases 7% bioavailability (not meal dependent) 80% renally excreted T 1/2 = 8-10 hours after single dose (14-17 hours after multiple dosages) Related to aptt (non-linear) and thrombin time and ecarin clotting time (both linear), but not INR

17 Percent/Year Stroke Prevention in AF Dabigatran Etexilate vs Warfarin (RE-LY) P =.003 Dabigatran 110 mg Dabigatran 150 mg Warfarin INR *P<.001 P<.001 Dabigatran 110 mg is not FDA approved for this indication; for informational purposes only P<.001 Avg TTR: 67% P<.001 P= Stroke/Systemic Embolism Major Bleed Intracranial Hemorrhage *Noninferiority; Superiority. MI = myocardial infarction; RE-LY = Randomized Evaluation of Long-term Anticoagulation Therapy. Connolly SJ, et al. N Engl J Med. 2009;361(12): Connolly SJ, et al. N Engl J Med. 2011;363: MI

18 ACCF/AHA/HRS 2011 Focused Update to the Guidelines for Antithrombotic Therapy to Prevent Stroke Risk Category No risk factors One moderate-risk factor (Age 75 yrs, HTN, CHF, LVEF 35%, and diabetes) Any high-risk factor or more than 1 moderate-risk factor (Previous stroke, TIA or embolism, mitral stenosis, and Prosthetic heart valve*) Recommended Therapy Aspirin, 81 to 325 mg daily Aspirin 81 to 325 mg daily, or Warfarin (INR 2.0 to 3.0, target 2.5) Dabigatran Warfarin (INR 2.0 to 3.0, target 2.5)* Dabigatran ESC Guidelines use CHA 2 DS 2 -VASc, rather than CHADS 2, risk stratification, with score 2 requiring warfarin or dabigatran. *If mechanical valve, target INR >2.5. Dabigatran is useful as an alternative to warfarin in patients with AF and risk factors for stroke or systemic embolization who do not have a prosthetic heart valve or hemodynamically significant valve disease, severe renal failure, or advanced liver disease. LV = left ventricular; INR = international normalized ratio; TIA = transient ischemic attack. Fuster V, et al. J Am Coll Cardiol 2006;48:e149-e246. Wann SL, et al. Heart Rhythm. 2011;8:e1-8.

19 Characteristics of New and Investigational Oral Anticoagulants Drug Dabigatran Rivaroxaban Apixaban Betrixaban Edoxaban Mechanism of action Thrombin inhibitor Factor Xa inhibitor Factor Xa inhibitor Factor Xa inhibitor Factor Xa inhibitor T 1/ hours 5-9 hours 12 hours hours 6-12 hours Regimen BID QD, BID BID QD QD Peak to trough Renal excretion of absorbed drug Potential for drug interactions ~7x 12x (QD) 3-5x ~3x ~3x ~80% 36%-45% 25%-30% ~15% 35% P- glycoprotein inhibitor CYP3A4 substrate and P- glycoprotein inhibitor CYP3A4 substrate and P- glycoprotein inhibitor Not substrate for major CYPs CYP3A4 substrate and P- glycoprotein inhibitor T 1/2 = half-life; CYP3A4 = cytochrome P450 3A4. Usman MH, et al. Curr Treat Cardiovasc Med. 2008;10(5): Piccini JP, et al. Curr Opin Cardiol. 2010;25(4):

20 Event Rate / 100 Pt-Yrs ROCKET AF: Primary Efficacy and Safety Outcomes Rivaroxaban* Warfarin P=0.02 On Treatment ITT Major Bleeding Intracranial Bleeding *P<0.001 for noninferiority of rivaroxaban vs warfarin; Superiority. Event rates are per 100 patient-years. Based on safety on treatment or ITT through site notification populations. Patel MR, et a. N Engl J Med Published online August 30, P=0.12 Stroke and Non-CNS Embolism P=0.58 Rivaroxaban was recently approved by the FDA for stroke prevention in AF. Safety P=0.02

21 Event Rate / 100 Pt-Yrs ARISTOTLE Trial: Efficacy and Safety Results Apixaban** Warfarin P=0.047 P < P < P= P < Stroke or Systemic Embolism Death from Any Cause ISTH Major Bleeding Intracranial Bleeding Net Clinical Outcomes* *Net clinical outcomes: Stroke, system embolism, or major bleeding. **Apixaban is not FDA approved. Granger CB, et al. N Engl J Med Published online August 30, 2011.

22 Rate vs Rhythm Control ACC/AHA/ESC Before choosing rate control as a long-term strategy, the clinician should consider how permanent AF is likely to affect the patient in the future. RACE and AFFIRM do not necessarily apply to younger patients without heart disease or to patients whose dependency upon sinus rhythm is likely to change appreciably over time. This makes it important to ensure that a window of opportunity to maintain sinus rhythm is not overlooked early in the course of management of a patient with atrial fibrillation. Fuster et al. J Am Coll Cardiol. 2006;48:

23 Cumulative Mortality (%) AFFIRM: Primary Endpoint All-Cause Mortality Rhythm control Rate control The AFFIRM Investigators. N Engl J Med. 2002;347: (A) P= Time (years) No. of deaths Number (%) Rhythm: 0 80 (4) 175 (9) 257 (13) 314 (18) 352 (24) Rate: 0 78 (4) 148 (7) 210 (11) 275 (16) 306 (21)

24 AFFIRM: On-Treatment Post Hoc SR Is Associated With Better Survival SR Warfarin -54% -47% 0.54 ( ; P<.0001) 0.47 ( ; P<.0001) Digoxin 1.50 ( ; P<.0001) +50% AADs 1.41 ( ; P=.0005) +41% Risk Ratio Other significant variables in model: age, CAD, CHF, smoking, stroke/tia, LVEF, mitral regurgitation. The AFFIRM Investigators. Circulation. 2004;109:

25 Clinical Considerations for Management Strategy of Rate Versus Duration and patterns of AF Type and severity of symptoms Associated cardiovascular disease Potential for changes in cardiac function over time Fuster et al. J Am Coll Cardiol. 2006;48:

26 Rate vs Rhythm and Physician Characteristics Assessed patient and physician characteristics associated with the choice of rate or rhythm control strategy in hospital 155,731 hospitalizations from 464 hospitals 48% rhythm control 52% rate control Care by a noncardiologist and increasing age >65 years were associated with lower odds of rhythm vs rate control (OR 0.33, 95% CI, for family, general, and internal medicine vs cardiology) Warfarin use was greater in the rhythm control group compared with the rate control group Lapointe et al. Am J Cardiol. 2008;101(8):

27 Rate Control

28 Agents for Heart Rate Control Nonacute and Chronic Maintenance Beta blockers Metoprolol Carvedilol Atenolol Calcium channel blockers Diltiazem Verapamil Digoxin Fuster et al. J Am Coll Cardiol. 2006;48:

29 What Is Adequate Rate Control? Adequate rate control is critical to avoid tachycardia-mediated cardiomyopathy beats per minute at rest AND beats per minute with exertion Criteria vary with age May be evaluated using 24-hour Holter recording Fuster et al. J Am Coll Cardiol. 2006;48:

30 RACE II 614 patients with permanent AF Lenient rate control: resting heart rate <110 bpm (97.7% met target) Strict rate control: resting heart rate <80 bpm and heart rate during moderate exercise <110 bpm (67% met target) Primary outcome: composite of death from CV causes, hospitalization for heart failure, and stroke, systemic embolism, bleeding, and lifethreatening arrhythmic events Incidence of primary outcome at 3 years Lenient: 12.9% Strict: 14.9% Van Gelder IC et al., NEJM 2010;362:

31 RACE II The mean (±SD) resting heart rate at the end of dose-adjustment: Lenient control: 93±9 bpm in the Strict-control: 76±12 bpm (P<0.001) At the end of the follow-up period: Lenient-control: 85±14 bpm Strict-control group: 76±14 bpm (P<0.001) Van Gelder IC et al., NEJM 2010;362:

32 Rhythm Control

33 Pharmacologic Management of Patients With Recurrent Paroxysmal Atrial Fibrillation Sinus Rhythm Maintenance Recurrent Paroxysmal AF Minimal or no symptoms Disabling symptoms in AF Anticoagulation and rate control as needed Anticoagulation and rate control as needed No drug for prevention of AF Fuster et al. J Am Coll Cardiol. 2006;48: AAD therapy AF ablation if AAD treatment fails

34 2011 ACCF/AHA/HRS Guidelines: Antiarrhythmic Approaches to Maintain SR in Patients with Recurrent PAF or Persistent AF* Maintenance of SR No (or minimal) heart disease HTN CAD HF Dronedarone Flecainide Propafenone Sotalol No Substantial LVH Yes Dofetilide Dronedarone Sotalol Amiodarone Dofetilide Amiodarone Dofetilide Catheter ablation Dronedarone Flecainide Propafenone Sotalol Amiodarone Amiodarone Catheter ablation Catheter ablation Amiodarone Dofetilide Catheter ablation Catheter ablation A Safety-Driven Approach *Within each box, drugs are listed alphabetically and not in order of suggested use. ACCF/AHA/HRS = American College of Cardiology Foundation/American Heart Association/Heart Rhythm Society; CAD = coronary artery disease; ESC = European Society of Cardiology; LVH = left ventricular hypertrophy; NYHA = New York Heart Association. Wann LS, et al. Circulation. 2011:123: Camm AJ, et al. Eur Heart J. 2010:31;

35 Outpatient Treatment of Recent-Onset Atrial Fibrillation with the Pill-in-the-Pocket Approach Flecainide 300 mg orally (200 mg for <70 kg) Propafenone 600 mg orally (450 mg for <70 kg) Treatment was successful in 534 episodes (94 percent) Time to resolution of symptoms was 113±84 minutes Among the 165 patients with recurrences, the drug was effective during all the arrhythmic episodes in 139 patients (84 percent) Alboni, P. et al., N Engl J Med 2004;351:

36 Patients in SR at 1 Year (%) Efficacy of AADs in AF Trials Amiodarone Dronedarone Sotalol Class IC Placebo CTAF SAFE-T AFFIRM DAFNE* EURIDIS* ADONIS EURIDIS/ DIONYSOS *At 6 months; Mean follow-up 7 months. ADONIS Pooled CTAF = Canadian Trial of Atrial Fibrillation; SAFE-T = Sotalol Amiodarone Atrial Fibrillation Efficacy Trial; DAFNE = Dronedarone Atrial Fibrillation Study after Electrical Cardioversion; EURIDIS = European Trial in Atrial Fibrillation or Flutter Patients Receiving Dronedarone for the Maintenance of Sinus Rhythm; ADONIS = American-Australian- African Trial with Dronedarone in Atrial Fibrillation or Flutter for the Maintenance of Sinus Rhythm; DIONYSOS = Randomized, Double-blind Trial to Evaluate the Efficacy and Safety of Dronedarone vs Amiodarone for at Least 6 Months for the Maintenance of Sinus Rhythm in Patients with AF. Courtesy of G Naccarelli, MD. Roy D, et al. Am J Cardiol. 1997;80: Singh BN, et al. N Engl J Med. 2005;352(18): AFFIRM Investigators. J Am Coll Cardiol. 2003;42: Touboul P, et al. Eur Heart J. 2003;24: Singh BN, et al. N Engl J Med. 2007;357(10): Le Heuzey JY, et al. J Cardiovasc Electrophysiol. 2010;21:

37 Dronedarone Dronedarone CH 3 SO 2 HN O O O (CH 2 ) 3 CH 3 (CH 2 ) 3 CH 3 I O(CH 2 ) 3 N (CH 2 ) 3 CH 3 (CH 2 ) 3 CH 3 De-iodinated amiodarone analog Predictable pharmacokinetics (T1/2 of hrs; BID dosing) Hepatically cleared Low incidence of side effects Amiodarone O I O(CH 2 ) 2 N CH 2 CH 3 CH 2 CH 3 Low proarrhythmia (safe to use as outpatient) No evidence of thyroid or pulmonary toxicity but rare cases of serious hepatotoxicity Kathofer S, et al. Cardiovasc Drug Rev. 2005;23(3): Hynes BJ, et al. Future Cardiol. 2005;1(2): US Food and Drug Administration. Accessed March 10, 2011.

38 Dronedarone: Pharmacological Effects Na channel blocker (10X stronger than amiodarone) Antiadrenergic effect (non-competitive βrc binding) Potassium channel blocker (I Kr ; I Ks ; I Ach-Ado ; I K1 ); (I Ach-Ado 100X stronger than amiodarone) Calcium channel blocker (I Ca-L ) Special considerations and contraindications Contraindicated in Class IV HF or lesser HF with recent decompensation Potential liver toxicity/hepatic function impairment Drug interactions similar to amiodarone, except no significant interaction with warfarin Exposure to dabigatran is higher when it is administered with dronedarone Should not be used in permanent AF Patel C, et al. Circulation. 2009;120: Multaq [package insert]. Bridgewater, NJ: sanofi-aventis U.S. LLC; 2011.

39 Cumulative Incidence (%) ATHENA Primary Outcome: First Cardiovascular Hospitalization or Death Primary End Point: Reduction in CV Hospitalization or Death From Any Cause (Entirely Attributable to Effect on CV Hospitalization) Placebo Dronedarone 24% RRR HR=0.76 (95% CI: ) P< Months Patients at Risk Placebo Dronedarone Components of End Point (as First Event) Placebo (n=2327) n (%) Mean follow-up 21± 5 months. RRR = relative risk reduction. Hohnloser SH, et al. N Engl J Med. 2009;360: Dronedarone 400 mg BID (n=2301) n (%) CV hospitalization 856 (36.8) 669 (29.1) Death from any cause 57 (2.4) 58 (2.5)

40 ANDROMEDA: Study Primary Endpoint Primary endpoint The primary composite endpoint was all-cause mortality Results or hospitalization for heart failure vs placebo Analysis up to study discontinuation Placebo (n=317) Dronedarone 800 mg/d (n=310) Number of patients who died Relative risk (relative to placebo) % CI 1.071, P value The excess in mortality was primarily related to an excess of heart failure related deaths. CI = confidence interval. Kober L, et al. NEJM 2008;358;

41 PALLAS Study Permanent Atrial Fibrillation Outcome Study Using Dronedarone on Top of Standard Therapy Hypothesis Dronedarone would reduce major vascular events in high-risk permanent atrial fibrillation Methods/Inclusion criteria Patients > 65 years of age > 6-month history of permanent atrial fibrillation Risk factors for major vascular events Patients randomized to dronedarone 400 mg bid vs. placebo Coprimary outcomes Stroke, MI, systemic embolism or CV death Unplanned CV hospitalization or death Connolly, SJ et al. Dronedarone in high-risk permanent atrial fibrillation. N Engl J Med. 2011; DOI: /NEJMoa Published Nov 14, Accessed Nov 15, 2011.

42 Rate per 100 Patient-Years PALLAS Trial: Dronedarone in Permanent AF After PALLAS enrolled 3236 patients, the study was stopped for safety reasons. P< Dronedarone Placebo P< P= Stroke, MI, Systemic Embolism, or CVD 12.9 Death or Unplanned CV Hospitalization Connolly, SJ et al. Dronedarone in high-risk permanent atrial fibrillation. N Engl J Med. 2011; DOI: /NEJMoa Published Nov 14, Accessed Nov 15, P=0.049 P= P= Death Stroke Hospitalization for HF 10.7 HF Episode or Hospitalization

43 CATHETER ABLATION

44 2011 ACCF/AHA/HRS Guidelines: Catheter Ablation is Still Second Tier Therapy Maintenance of SR No (or minimal) heart disease HTN CAD HF Dronedarone Flecainide Propafenone Sotalol No Substantial LVH Yes Dofetilide Dronedarone Sotalol Amiodarone Dofetilide Amiodarone Dofetilide Catheter ablation Dronedarone Flecainide Propafenone Sotalol Amiodarone Amiodarone Catheter ablation Catheter ablation Amiodarone Dofetilide Catheter ablation Catheter ablation A Safety-Driven Approach ACCF/AHA/HRS = American College of Cardiology Foundation/American Heart Association/Heart Rhythm Society; CAD = coronary artery disease; ESC = European Society of Cardiology; LVH = left ventricular hypertrophy; NYHA = New York Heart Association. Wann LS, et al. Circulation. 2011:123: Camm AJ, et al. Eur Heart J. 2010:31;

45 Indications for Catheter AF Ablation Symptomatic AF refractory or intolerant to at least 1 Class I or III AAD Selected symptomatic patients with HF and/or reduced ejection fraction As an alternative to device implantation to support AAD therapy in bradycardic patients Presence of an LA thrombus is a contraindication to catheter ablation of AF Discontinuation of anticoagulation is not an indication for ablation Calkins H, et al. Heart Rhythm. 2007;4(6):

46 Meta-Analysis of Catheter Ablation vs Drug Therapy Statistics for Each Study Risk Lower Upper Study Name Ratio Limit Limit Z P Risk Ratio and 95% CI Thai study Natale et al APAF study CACAF study Haissaguerre et al Morady et al APAF = Ablation for Paroxysmal Atrial Fibrillation; CACAF = Catheter Ablation for the Cure of Atrial Fibrillation. Nair GM, et al. J Cardiovasc Electrophysiol. 2009;20(2): Favors Ablation Favors Medical Therapy

47 Rates (%) Success Rates With Ablation Worldwide Survey Success without AADs Success with AADs Overall success >24 Range of followup (months) Cappato et al. Circulation. 2005;111: (B).

48 LV End-Diastolic Diameter (mm) LV Ejection Fraction (%) LV Ejection Fraction (%) LV Ejection Fraction (%) Effect of AF Ablation on LVEF and Chamber Size in Patient with and without Concurrent Heart Disease and Rate Control P < Ejection Fraction P < Months P < P < Heart Disease No Concurrent Heart Disease Concurrent Heart Disease 0 12 Months P < P < P=0.001 LV ED Diameter P= Months Hsu LF, et al. NEJM 2004; 351: P=0.02 P= Rate Control Inadequate Rate Control Adequate Rate Control Months 12 P < P < 0.001

49 Patients (%) Complication Rates for Catheter Ablation Cappato et al. Circulation. 2005;111: (B)

50 CABANA Trial Recent-onset AF eligible for ablation or drug therapy 65 years old or < 65 years old with 1 risk factor for CAD or stroke Primary Ablation (technique at operator discretion) Drug Therapy (rate or rhythm control [at operator discretion] with anticoagulation) Discontinued Anticoagulation Continued Anticoagulation Packer. Presented at: 2005 Scientific Sessions of the American Heart Association; November 13-16, 2005; Dallas, TX(A i ).

51 Summary AF is a common disease that is increasing in prevalence. Atrial electrical and structural remodeling takes place early and progresses, making the return to SR more difficult with longer duration of AF. Newer anticoagulants provide more options for stroke prophylaxis in patients with AF Decisions about rate and rhythm control in AF depend on the frequency of episodes and the severity of patients symptoms. Catheter ablation is curative in many patients who have failed antiarrhythmic drug therapy.

52 Post-Test Question #1. A 69 year old Caucasian female is referred from her primary care physician s office after she presented with episodic palpitations and was found to have new onset atrial fibrillation. She has a past medical history of hypertension that is well controlled with lisinopril 10 mg daily. There is no history of diabetes mellitus, prior stroke or transient ischemic attack, or cardiovascular disease. What are her CHADS 2 and the CHA 2 DS 2 -VASc scores? a) 1 and 1 b) 1 and 2 c) 1 and 3 d) 1 and 4 CHADS 2 score of 1: Hypertension CHA 2 DS 2 -VASc score of 3: hypertension, female, and age between 65 to 74 years

53 Post-Test Question #2. What anti-thrombotic therapy would you initiate to prevent a risk of stroke in this patient? a) None, her risk for stroke is low b) Aspirin 325 mg daily c) Aspirin 325 mg + clopidogrel 75 mg daily d) Warfarin to maintain a therapeutic INR between 2 and 3 Although her CHADS 2 score is 1, her CHA 2 DS 2 - VASc score is 3. This gives her a stroke risk of 3.2%, that is best minimized with warfarin.

54 Post-Test Question #3. A 73 year old patient is referred for preoperative evaluation for knee replacement surgery because her ECG showed previously undiagnosed atrial fibrillation. She denies cardiovascular symptoms, but she has treated hypertension and a history of myocardial infarction. There is no history of diabetes mellitus, stroke or TIA, or bleeding problems. She denies illicit drug or alcohol use. Her weight is 92.7 kg, Her serum creatinine is 3.2 mg/dl and estimated creatinine clearance is 14 ml/min; liver function is normal. The ECG shows AF with an average ventricular rate of 75 bpm. Echocardiogram shows left ventricular hypertrophy and left atrial enlargement.

55 Which anticoagulation strategy would you recommend? a) Aspirin b) Warfarin c) Dabigatran d) Rivaroxaban Both dabigatran and rivaroxaban are cleared by the kidneys and should be avoided when creatinine clearance is less than 15 ml/min.