Presentation is loading. Please wait.

Presentation is loading. Please wait.

Section II: Clinical Management of AFib. Section II. Clinical Management of AFib 1. Clinical Evaluation of AFib 2. Treatment Options for AFib Cardioversion.

Similar presentations


Presentation on theme: "Section II: Clinical Management of AFib. Section II. Clinical Management of AFib 1. Clinical Evaluation of AFib 2. Treatment Options for AFib Cardioversion."— Presentation transcript:

1 Section II: Clinical Management of AFib

2 Section II. Clinical Management of AFib 1. Clinical Evaluation of AFib 2. Treatment Options for AFib Cardioversion Drugs to prevent AFib Drugs to control ventricular rate Drugs to reduce thromboembolic risk Non-pharmacological options

3 1. Clinical Evaluation of AFib

4 Clinical Evaluation Minimum – History and Physical examination – Electrocardiogram – Trans-thoracic echocardiogram – Blood tests of thyroid, renal and hepatic function Discretionary – Six-minute walk test – Exercise testing – Holter monitoring or event recording – Trans-oesophageal echocardiography – Electrophysiological study – Chest radiograph ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation J Am Coll Cardiol (2006) 48: 854

5 Opportunistic Case Finding In patients presenting with symptoms commonly associated with AFib: – breathlessness/dyspnoea – palpitations – syncope/dizziness – chest discomfort Manual pulse palpation should be performed to determine the presence of an irregular pulse that may indicate underlying AFib NICE recommendation: Developed by National Collaborating Centre for Chronic Conditions at the Royal College of Physicians; Atrial fibrillation: full guideline DRAFT (January 2006)

6 Restore and maintain sinus rhythm whenever possible Prevent thromboembolic events In order to: –Reduce symptoms and improve QoL –Minimize impact of AFib on cardiac performance –Reduce risk of stroke –Minimize cardiac remodeling Primary Therapeutic Aims in AFib ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation J Am Coll Cardiol (2006) 48: 854

7 2. Treatment Options for AFib

8 Treatment Options for AFib Cardioversion Pharmacological Electrical Drugs to prevent AFib Antiarrhythmic drugs Non-antiarrhythmic drugs Drugs to control ventricular rate Drugs to reduce thromboembolic risk Non-pharmacological options Electrical devices (implantable pacemaker and defibrillator) AV node ablation and pacemaker implantation (ablate & pace) Catheter ablation Surgery (Maze, mini-Maze)

9 Treatment Options for AFib Cardioversion

10 Cardioversion of AFib Pharmacological – Early onset AFib – Long-standing AFib Electrical – Transthoracic

11 Cardioversion of AFib Prompt treatment essential Limit duration to minimize cardiac remodelling Avoid anticoagulation therapy – (necessary for arrhythmias that last >48 hours) Avoid prolonged hospital recovery Improve quality of life

12 Pharmacological Cardioversion

13 More effective in recent-onset AFib – Class IA-IC-III drugs administered IV – Class IC favoured in non-cardiopathic patients – Class III favoured in cardiopathic patients or those with delays in conduction Oral loading can be performed with class IC drugs – Flecainide ( mg) – Propafenone ( mg)

14 Pharmacological Cardioversion Recent onset AFib

15 Oral Loading with Class IC Drugs for Recent Onset AFib Capucci A, et al. Am J Cardiol (1994) 74: SR (%) Propafenone 600 mg Flecainide 300 mg Placebo 3 hours8 hours 0 p<0.001 vs. placebo

16 Cardioversion of Paroxysmal AFib with Class IC Drugs Paroxysmal AFib (<48h), good LVEF IV 2 mg/kg mg/kg/min, maintenance Oral administrationflecainide 300 mg propafenone 600 mg Mean efficacy:80% Mean time of efficacy: 3h Proarrhythmia:FLA 1:1 ECG monitoring necessary (<0.5%) with patients in resting condition Class IC drugs (propafenone, flecainide)

17 Risk with Class IC Drugs: Transformation of AFib into Atrial Flutter with 1:1 AV Conduction Flecainide

18 Treatment Out-of-Hospital with Class IC Drugs Symptomatic, rare episodes of AFib Recent onset AFib No structural heart disease Prior hospital experience Good physician-patient relationship Resting conditions for at least 4 hours

19 Pill-in-the-Pocket In a selected (no or mild HD), risk-stratified patient population with recurrent AFib not currently taking AADs – 79% developed ≥ 1 episodes of recurrent AFib during 15 ± 5m follow-up – Acute oral flecainide or propafenone successfully terminated 94% of episodes within 113 ± 84 min, with side effects in 7% of patients Alboni P, et al. N Engl J Med (2004) 351: 2384

20 Pill-in-the-Pocket 0 50 Number per month 25 Prior to enrolmentDuring follow-up Hospitalisation p< Calls to ER Number per month p<0.001 Alboni P, et al. N Engl J Med (2004) 351: 2384

21 Connolly SJ Circulation (1999) 100: 2025 Control drugn Primary endpoint Duration of study OR of SR with amiodaronep Cowan et alDigoxin IV34 Conversion to sinus rhythm 24 h1.11NS Hou et alDigoxin IV5024 h Cotter et alPlacebo8024 h Galve et alPlacebo10024 h Donovan et alPlacebo6424 h1.05NS Donovan et alFlecainide6624 h0.86NS Nos et alVerapamil243 h 77% amiod./ 0% verap <0.001 McAlister et alQuinidine368 h Pilati et alQuinidine7524 h1.09NS Kerin et alQuinidine3224 h1.07NS Di Biasi et alPropafenone4024 h1.15NS Larbuisson et alPropafenone8424 h1.22NS Chapman et alProcainamide2612 h0.99NS Moran et alMagnesium sulfate4224 h0.64<0.05 Conversion to SR with Amiodarone IV (randomized studies)

22 Amiodarone for Cardioversion of Recent-Onset AFib: Meta-analysis Khan IA, et al. Int J Cardiol (2003) 89: 239 Amiodarone IV (3-7 mg/kg ± infusion g/day) Amiodarone oral (25-30 mg/kg) Time to conversion > 6-8 h Amiodarone > 1.5 g/day IV > placebo Amiodarone mg/kg oral > placebo Amiodarone not > other AADs Safe in patients with structural cardiopathies and low LVEF Conversion (%) Bolus + infusion Bolus only 2-4 h8 h

23 Amiodarone Single Oral Administration for Cardioversion of Recent Onset AFib Peuhkurinen K, et al. Am J Cardiol (2000) 85: Patients in AFib (%) Amiodarone Placebo Time to conversion (hours) 24

24 Flecainide IV vs Amiodarone IV for Cardioversion in Recent-Onset AFib Donovan KD, et al. Am J Cardiol (1995) 75: Cardioversion (%) (hours) p=0.007p=0.001 Amiodarone Flecainide Placebo

25 Pharmacological Cardioversion Long-lasting AFib

26 Effect of Duration on Efficacy of Pharmacological Cardioversion Reisinger J, et al. Am J Cardiol (1998) 81: patients with AFib <6 months Sotalol Flecainide * p=0.005 Total 52* 23 <24 hours 69* 31 <7 days <6 months 00 0

27 Amiodarone Cardioversion in Persistent AFib Kochiadakis GE, et al. Am J Cardiol (1999) 83: patients with AFib >48 hours Placebo Amiodarone p<0.001 Total 48 0 LA (mm) >45 < LVEF (%) >50 < AFib (m) >1 < AB Sinus rhythm (%)

28 Conversion of Atrial Flutter or AFib with Ibutilide IV Stambler BS, et al. Circulation (1996) 94: Sinus rhythm (%) p< Ibutilide 0 Placebo Sinus rhythm (%) p< AFlutter 0 AFib 266 patients Adverse effects: 8.3% polymorphic ventricular tachycardia

29 Conversion of Atrial Flutter or AFib with Ibutilide IV Glatter K, et al. Circulation (2001) 103: 253 Effect “on top” of long-term amiodarone Recovery of SR (%) AFlutter 0 AFib 70 patients (57 AFib, 13 AFlutter) Ibutilide 2 mg 39 54

30 Electrical Cardioversion (transthoracic)

31 Technical Aspects Impedence Position of paddles Pressure applied to paddles Waveform The efficacy of electrical cardioversion depends on the density of current delivered to the atrial myocardium, which is dependent on:

32 Transthoracic Cardioversion of Atrial Fibrillation Comparison of Rectilinear Biphasic vs Damped Sine Wave Monophasic Shocks Suneet Mittal, Shervin Ayati, Kenneth M. Stein, David Schwartzman, Doris Cavlovich, Patrick J. Tchou, Steven M. Markowitz, David J. Slotwiner, Marc A. Scheiner, Bruce B. Lerman. Circulation 2000; 101:

33 Defibrillation Waves Mittal S, et al. Circulation (2000) 101: 1282 Monophasic waveBiphasic wave Ampere msec Ampere msec 30

34 Cumulative Efficacy of Cardioversion Mittal S, et al. Circulation (2000) 101: 1282 Monophasic or biphasic shock Efficacy of cardioversion (%) p< J J J J J J J J 94 0 p<0.005 MonophasicBiphasic

35 Biphasic vs Monophasic Shock Waveform for Conversion of Atrial Fibrillation The Results of an International Randomized, Double-Blind Multicenter Trial RL Page, RE Kerber, JK Russel, T Trouton, J Waktare, D Gallik, JE Olgin, P Ricard, GW Dalzell, R Reddy, R Lazzara, K Lee, M Carlson, B Halperin, GH Bardy, for the BiCard Investigators. JACC (2002) 39:

36 Dermal Injury Dependent on Waveform Page RL, et al. J Am Coll Cardiol (2002) 39: Biphasic Monophasic None (no erythema) Mild (no tenderness) Moderate (tenderness) Severe (blistering) 0

37 Success of Monophasic (MP) and Biphasic (BP) Waveforms at Cumulative Energy Levels Adgey AA & Walsh SJ Heart (2004) 90: 1493

38 Success of Cumulative Shocks for Different Biphasic Devices Adgey AA & Walsh SJ Heart (2004) 90: 1493

39 Electrical Cardioversion Pharmacological pretreatment and management of recurrence

40 Failure of Electrical Cardioversion Van Gelder IC, et al. Am J Cardiol (1999) 84: 147R Sinus rhythm (%) 0 2 min Immediate recurrent AFib No conversion Early recurrent AFib Late recurrence AFib 2 weeks1 year cardioversion

41 Recurrence Following Cardioversion: AFFIRM Study Raitt MN, et al. Am Heart J (2006) 151: 390 AFFIRM:most recurrences occur within 2 months of cardioversion Time (years) Patients with AF Recurrence (%) Log rank statistic = p< Rate control:563,3 (0)167,383 (69)96,440 (80)42,472 (87)10,481 (92)2,484 (95) Rhythm control:729,2 (0)344,356 (50)250,422 (60)143,470 (69)73,494 (75)18,503 (79) N, Events (%) Rate control Rhythm control Treatment Arm

42 Immediate Recurrence of AFib Following Successful Electrical Cardioversion

43 AuthorsnERAF (%)Timing Bertaglia90287 days Bianconi hours Botto days Daoud33795 min De Simone days Tieleman61365 days Villani hours Yu50261 min Immediate/Early Recurrence of AFib After Electrical Cardioversion

44 Effect of Atrial Fibrillation Duration on Probability of Immediate Recurrence after Transthoracic Cardioversion H Oral, M Ozadyn, C Sticherling, H Tada, C Scharf, A Chugh, SWK Lai, F Pelosi, BP Knight, SA Strickeberger, F Morady. JCE 2003; 14: 182-5

45 Immediate Recurrence of AFib (IRAF) According to the Duration of Arrhythmia Oral H, et al. J Cardiovasc Electrophysiol (2003) 14: 1 hr 1-24 hrs 1-7 days 7-30 days days days days >365 days Duration of AFib Prevalence of IRAF (%)

46 Immediate and Early Recurrence Following Cardioversion Authors Bertaglia Bianconi Botto Daoud De Simone Tieleman Villani Yu Pts (n) ERAF (%) Timing 7 days 24 hours 7 days 5 min 7 days 5 days 24 hours 1 min

47 Oral Propafenone Before Electrical Cardioversion in Persistent AFib Bianconi L, et al. J Am Coll Cardiol (1996) 28: 700 Effect on early recurrence of arrhythmia Sinus rhythm (%) p< Complex atrial arrhythmia (%) p< minutes min24 min48 min 0 Placebo Propafenone 18 52

48 Effect of Pre-treatment with Oral Amiodarone Capucci A, et al. Eur Heart J (2000) 21: Conversion (%) p<0.005 SR before ECV 0 GIK Amiodarone No treatment Conversion (%) p<0.05 SR with cardioversion 0 GIK Amiodarone No treatment No differences in energy for cardioversion

49 Chenner KS, et al. Eur Heart J (2004) 25: 144 Stable anticoagulation for 2 weeks Short-term Amiodarone 20 (32%) Placebo 2 (5%) Long-term Amiodarone 30 (49%) Short-term Amiodarone 29 (47%) Placebo 6 (16%) Long-term Amiodarone 34 (56%) Sinus Rhythm at 52 weeks Sinus Rhythm at 8 weeks Short-term Amiodarone 48 Placebo 30 Long-term Amiodarone 48 Sinus Rhythm Short- and Long-term Treatment with Amiodarone after Cardioversion Reduces Recurrence DCCV 100 Chemical 26 Short-term Amiodarone 62 Placebo 38 Long-term Amiodarone Protocol violation = 4; Withdrew consent = 7 Randomization 172

50 Effect of Pre-treatment with Ibutilide IV Oral H, et al. N Engl J Med (1999) 340: 1849 Successful cardioversion in all patients given ibutilide and in 14/50 patients failing cardioversion alone The mean energy for defibrillation was less with ibutilide Sustained polymorphic tachycardia in 2/64 (3%) patients treated with ibutilide within 15 min of the infusion Patients (%) 0 SR after ECV SR before ECV AFib IBUNo IBU

51 Pre-treatment with Verapamil in Patients with Persistent or Chronic Atrial Fibrillation Who Underwent Electrical Cardioversion A De Simone, G Stabile, DF Vitale, P Turco, M Di Stasio, F Petrazzuoli, M Gasparini, C De Matteis, R Rotunno, T Di Napoli. J Am Coll Cardiol (1999) 34: 810-4

52 Pre-treatment with Verapamil for Reducing Recurrence post-ECV De Simone A, et al. J Am Coll Cardiol (1999) 34: week 30 0 Recurrence (%) 3 months PFN + VER PFN PFN - VER p=0.01 p=0.04 p=0.02 p=0.04

53 Effects of Pre-treatment with Verapamil on Early Recurrences after Electrical Cardioversion of Persistent Atrial Fibrillation A Randomised Study E Bertaglia, D D’Este, A Zanocco, F Zerbo, P Pascotto. Heart (2001) 85:

54 Effect of Pre-treatment with Verapamil on Early Recurrence Following ECV Bertaglia E, et al. Heart (2001) 85: A randomised trial (90 patients with amiodarone) Recurrence (%) Amio + Ver Amio 6 h NS 7 d NS 30 d NS Follow-up

55 Effect of Verapamil on Immediate and Early Recurrence after Cardioversion of AFib Effectiveness demonstrated – A De Simone et al (JACC 1999) – E Daoud et al (JCE 2000) – GQ Villani et al (AHJ 2002) – A De Simone et al (AJC 2002) – GL Botto et al (JACC 2002) Not efficacious – E Bertaglia et al (Heart 2001) – T Van Noord et al (JCE 2001) – H Ramanna et al (JACC 2001)

56 Cardioversion of AFib and Maintenance of SR Van Gelder IC, et al. Arch Int Med (1996) 156: Maintenance of SR (%) ECV, no AADs Serial ECV Months post-cardioversion

57 Success of Serial External Electrical Cardioversion of Persistent Atrial Fibrillation in Maintaining Sinus Rhythm E Bertaglia, D D’Este, F Zerbo, F Zoppo, P Delise, P Pascotto. European Heart Journal (2002) 23:

58 Serial Electrical Cardioversion 90 patients with persistent AFib who had previously undergone at least one successful electrical cardioversion Randomization Cardioversion repeated up to 2 times in case of recurrent AFib within 1 month of the preceding electrical cardioversion (Group AGG) or Recurrences were left untreated (Group CTL) Bertaglia E, et al. Eur Heart J (2002) 23: 1522

59 Persistence of Sinus Rhythm During Long-term Follow-up Aggressive repeated ECV beneficial in highly recurrent persistent AFib days Bertaglia E, et al. Eur Heart J (2002) 23: 1522 Sinus rhythm (%)

60 2.Treatment Options for AFib Drugs to Prevent AFib

61 Drugs to Prevent AFib Antiarrhythmic drugs – Class I-III antiarrhythmics Non-antiarrhythmic drugs – ACE-I, ARBs – Statins – PUFA

62 Rationale for Drug Treatment to Prevent Recurrence Suppression of symptoms Avoidance of tachycardia-induced cardiomyopathy Reduction of thromboembolism Prevention of heart failure? Decrease of mortality?

63 Drugs to Prevent AFib Antiarrhythmics

64 Vaughan Williams Classification Type lA Disopyramide Procainamide Quinidine Type IB Lidocaine Mexiletine Type IC Flecainide Moricizine Propafenone Type II Beta-blockers Type III Amiodarone Bretylium Dofetilide Ibutilide Sotalol Type IV Calcium antagonists

65 Disopyramide mg Procainamide mg Quinidine mg Flecainide mg Propafenone mg Amiodarone mg Dofetilide mcg Sotalol mg Drugs to Maintain SR in Patients with AFib – Recommended Daily Doses

66 Even with the most effective AAD, such as amiodarone, long-term efficacy is low ~50% or less at 1 year Effectiveness of Current AADs

67 Prevention of Recurrence with AADs Lafuente-Lafuente C, et al. Arch Intern Med (2006) 166: 719 No. of Events/TotalPeto OR (95% Cl) Drugs studied No. of StudiesAntiarrhythmicControlp value Antiarrhythmic vs Control Class IA Disopyramide hydrochloride 240/7549/ ( )0.05 Quinidine sulfate7741/ / ( )<0.001 All class IA8781/ / ( )<0.001 Class IB All: aprindine hydrochloride, bidisomide 2639/781453/ ( )0.26 Class IC Flecainide acetate331/7156/ ( )<0.001 Propafenone hydrochloride 5376/720276/ ( )<0.001 All class IC9443/843342/ ( )<0.001 Class II All: metroprolol tartrate 1127/197140/ ( )0.16 Class III Amiodarone4200/428209/ ( )<0.001 Dofetilide2252/431274/ ( )<0.001 Sotalol hydrochloride9916/ / ( )<0.001 Dronedarone1116/15143/ ( )0.06 All class III151484/ / ( )<

68 Prevention of recurrence in studies comparing AADs with placebo or no treatment Quinidine Proportion without Recurrence (%) DisopyramidePropafenoneFlecainideAmiodaroneSotalol 0 Prevention of Recurrence with AADs Lafuente-Lafuente C, et al. Arch Intern Med (2006) 166: 719

69 Antiarrhythmic Drugs for Maintenance of Sinus Rhythm Tamariz L, et al. J Am Coll Cardiol 2003: 536A Meta-analysis of 18 randomized, controlled trials Quinidine Odds Ratio DisopyramidePropafenoneFlecainideAmiodaroneSotalol 0 Amiodarone > risk of non-cardiac adverse effects

70 Patients without AFib (%) Roy D, et al. N Engl J Med (2000) 342: 913 Amiodarone to Prevent Recurrence of AFib Follow-up (days) p<0.001 Sotalol Propafenone Amiodarone CTAF Study: mean follow-up 16 months

71 AFFIRM Substudy of First Anti- Arrhythmic Drug AFFIRM Study AFFIRM Investigators J Am Coll Cardiol (2003) 42: 20 Percent without recurrence Years Class I Drugs Amiodarone Amiodarone Sotalol Years 222 pts 256 pts 62% 23% 60% 38% p<0.001p=0.011

72 Probability of remaining in SR Follow-up (days) Sotalol Placebo Amiodarone SAFE-T Investigators Probability of remaining in SR All patients Patients with IHD Amiodarone Sotalol Placebo Singh BN, et al. N Engl J Med (2005) 352: 1861 Amiodarone and Solatolol Equivalent in Patients with Ischaemic Heart Disease

73 Hypothyroidism7.0% Hyperthyroidism1.4% Peripheral Neuropathy0.5% Lung Infiltrates1.6% Liver Dysfunction1.0% Bradycardia 2.4% Major Adverse Experiences Associated with Early Drug Discontinuation Amiodarone Trials Meta-analysis Investigators Lancet (1997) 350: 1417

74 Gastrointestinal events4.0% Pulmonary events2.6% Ocular events0.6% Other7.1% Amiodarone Discontinuations Associated with Major Adverse Events AFFIRM Investigators J Am Coll Cardiol (2003) 42: 20

75 Amiodarone meta-analysis41% at 2y CTAF18% at 16m PIAF25%at 1y AFFIRM12.3% at 1y Major Adverse Experiences Associated with Early Drug Discontinuation

76 Major Adverse Experiences Associated with AADs Lafuente-Lafuente C, et al. Arch Intern Med (2006) 166: 719 No. of Studies Withdrawals Peto OR (95% Cl) Drugs studied Antiarrhythmic vs Control Class IA Disopyramide hydrochioride23.85 ( ) Quinidine sulfate: higher dose53.58 ( ) Quinidine: lower dose20.81 ( ) Quinidine: all studies71.90 ( ) All class IA82.02 ( ) Class IB All: aprindine hydrochloride10.66 ( ) Class IC Flecainide acetate39.14 ( ) Propafenone hydrochloride51.69 ( ) All class IC91.93 ( ) Class II All: metoprolol tartrate13.16 ( ) Class III Amiodarone3,45.55 ( ) Dofetilide1,21.61 ( ) Sotalol hydrochloride: PAFAC, SOPAT20.95 ( ) Sotalol: rest of studies6,73.02 ( ) Sotalol: all studies8,91.47 ( ) Azimilide dihydrochloride + Dronedarone22.46 ( ) All class III14, ( )

77 Proarrhythmia Associated with AADs Lafuente-Lafuente C, et al. Arch Intern Med (2006) 166: 719 No. of Studies Proarrhythmia Peto OR (95% Cl) Drugs studied Antiarrhythmic vs Control Class IA Disopyramide hydrochloride2No Events Quinidine sulfate: higher dose54.56 ( ) Quinidine: lower dose21.53 ( ) Quinidine: all studies72.10 ( ) All class IA82.06 ( ) Class IB All: aprindine hydrochloride1No Events Class IC Flecainide acetate35.97 ( ) Propafenone hydrochloride51.52 ( ) All class IC93.41 ( ) Class II All: metoprolol tartrate17.96 ( ) Class III Amiodarone3, ( ) Dofetilide1, ( ) Sotalol hydrochloride: PAFAC, SOPAT21.42 ( ) Sotalol: rest of studies6, ( ) Sotalol: all studies8, ( ) Azimilide dihydrochloride + dronedarone23.30 ( ) All class III14, ( )

78 Proarrhythmic Profile of AADs Dysopiramide1-2% Quinidine2% Procainamide1-2% LidocainaRare Rare Rare Rare MexiletineRare Rare Rare Morizicine Rare Propafenone Rare Flecainide Rare Amiodarone<1% Ibutilide4-5%+Rare Sotalol2-5% TorsadeAtrial de PointeVFVT *Flutter 1:1 Bradyarrhythmia *More frequent in pts with structural HD or history of ventricular arrhythmias Friedman P, et al. Am J Cardiol (1998) 82: 50N

79 Overall Mortality Associated with AADs Lafuente-Lafuente C, et al. Arch Intern Med (2006) 166: 719 No. of Studies No. of Events/TotalPeto OR (95% Cl) p value Drugs studiedAntiarrhythmicControl Antiarrhythmic vs Control Class IA Disopyramide phosphate 22/750/ ( )0.16 Quinidine sulfate721/11284/ ( )0.07 All class IA823/12034/ ( )0.04 Class IB All: aprindine hydrochloride, bidisomide 29/7813/ ( )0.28 Class IC Flecainide acetate30/710/78Not estimableNA Propafenone hydrochloride 50/7202/ ( )0.05 All class IC91/8432/ ( )0.14 Class II All: metroprolol tartrate 13/1970/ ( )0.08 Class III Amiodarone413/4283/ ( )0.21 Dofetilide283/43183/ ( )0.88 Sotalol hydrochloride930/13915/ ( )0.06 Azimilide dihydrochloride + dronedarone 210/10424/ ( )0.63 All class III16136/329295/ ( )

80 Coplen SE, et al. Circulation (1990) 82: (%) Placebo Quinidine 3 month p< month p< month p< Mortality p< # of patients Mortality Associated with Class 1A Drugs Prophylaxis of AFib with quinidine: Meta-analysis of 6 randomized trials

81 Physician Visits Associated with AAD Use Over Time Fang FC et al. Arch Intern Med 2004; 164: Visits on medication (%) Visit (years) Quinidine Class IC Amiodarone Hydrochloride

82 Rhythm and Rate Control Studies PIAF, Lancet 2000 RACE, NEJM 2002 AFFIRM, NEJM 2002 PAF-2, Eur Heart J 2002 STAF, JACC 2003 HOT-CAFÉ, Chest 2004

83 Trial Age, y Mean Follow-up Thrombo- embolic complications % Mortality % Falk, RH. Circulation (2005) 111: 3141 Rhythm vs Rate Trials n AFFIRM42m Rate control Rhythm control RACE27m Rate control Rhythm control STAF22m Rate control Rhythm control NR PIAF12m Rate control Rhythm control NR 1.6 Hot Cafe20m Rate control Rhythm control NR NR Sinus rhythm (%) Warfarin (%)

84 Cumulative mortality (%) Rhythm control Rate control No. of deaths Rhythm control Rate control 10 Years 357 (13)80 (4)352 (24)0175 (9)314 (18) 210 (11)78 (4)306 (21)0148 (7)275 (16) p=0.08 AFFIRM Investigators N Engl J Med (2002) 347: 1825 AFib Follow-up Investigation of Rhythm Management (AFFIRM) No survival advantage of rhythm over rate (n=4060)

85 Testa L, et al. Eur Heart J (2005) 26: 2000 Study or sub-category Rate control (n/N) Rhythm control (n/N) Van Den Berg388/ /2033 SOLVD1/1016/104 TRACE2/1254/127 Ueng24/25632/266 CAPP971009/100 Total (95% CI) Weight (%) OR (95% CI Random) (0.74, 1.00) (0.02, 1.38) (0.09, 2.78) (0.43, 1.32) (0.38, 2.63) (0.73, 0.98) Total events: 424 (Rate control). 489 (Rhythm control) Test for heterogeneity chi-square=2.97; df=4; p=0.56; I 2 =0% Test for overall effect z=2.24; p=0.03 OR (95% CI Random) Rate control better Rhythm control better Odds Ratio for Combined Endpoint (All-cause Death + Thromboembolic Stroke) Meta-Analysis of Rhythm Control versus Rate Control Studies

86 Age at enrollment*< Coronary artery disease< Congestive heart failure< Diabetes< Stroke or transient ischemic attack< Smoking< First episode of AFib Sinus rhythm< Warfarin use< Digoxin use< Rhythm-control drug use Upper Covariate LowerpHR HR: 99% CL * per year of age AFFIRM Investigators Circulation (2004) 109: 1509 AFFIRM On-Treatment Analysis: SR but not AAD Use Associates with Improved Survival

87 AFFIRM Investigators Circulation (2004) 109: 1509 AFFIRM On-Treatment Analysis: SR Associates with Survival Implications In patients with AFib such as those enrolled in the AFFIRM study, warfarin improves survival. The presence of SR but not AAD use is associated with a lower risk of death. These results suggest that if an effective method for maintaining SR with fewer side effects were available, it might improve survival

88 Drugs to Prevent AFib Non-antiarrhythmic drugs

89 Non-antiarrhythmic Drugs to Prevent AFib ACE Inhibitors and Angiotensin Receptor Blockers Statins Polyunsaturated fatty acids (omega-3)

90 Non-antiarrhythmic drugs ACE Inhibitors and Angiotensin Receptor Blockers

91 Healey JS, et al. J Am Coll Cardiol (2005) 45: 1832 *Abstract only. ACEI = angiotensin-converting enzyme inhibitor; AF = atrial fibrillation; ARB = angiotensin receptor blocker; CHF = congestive heart failure; HTN = hypertension; LVD = left ventricular dysfunction; LVEF = left ventricular ejection fraction; LVH = left ventricular hypertrophy; NSR = sinus rhythm; Post-MI = post-myocardial infarction Author/Study, Date Patient GroupDrug No. Randomized Mean Follow-Up Mean LVEF HTN (%) Rate of AF in Control Group (%) ACE-I trials Van Den Burg, 1995AF, CHFLisinopril3084 daysn/a 64 Ueng, 2003AFEnalapril days (61-575) Vermes (SOLVD), 2003 LVD, CHF, NSR Enalapril yrs Pizetti (GISSI), 2001Post-MI, NSRLisinopril17,71142 daysn/a308 Pedersen (TRACE), 1999 Post-MI, LVD, NSR Trandolapril1, yrs33225 STOP-H2, 1999HTNEnalapril10, yrsn/a1008 CAPP, 1999HTNCaptopril6, yrsn/a1002 ARB trials CHARM, 2003*CHF, NSRCandesartan5, yrs39558 Madrid, 2002AFIrbesartan days (60-710) ValHeFT, 2003*CHF, NSRValsartan4,4092 yrs2878 Wachtell, (LIFE), 2003* HTN, LVH, NSR Losartan9, yrsn/a1006 Characteristics of ARB and ACE-I Studies in AFib

92 Study Treatment (n/N) Control (n/N) ACE inhibitor Van Den Berg2/77/11 SOLVD10/18645/188 TRACE22/79042/787 Ueng18/7032/75 CAPP117/ /5493 STOP-H2200/ /4409 GISSI665/ /8846 Sutotal (95% CI)1034/ /19809 Weight (%) RR (95% CI Random) (0.13, 1.57) (0.12, 0.43) (0.31, 0.87) (0.37, 0.97) (0.68, 1.11) (0.95, 1.32) (0.83, 1.02) (0.56, 0.93) Test for heterogeneity chi-square=32.58; df=6; p< Test for overall effect z=-2.53; p=0.01 Effect of Treatment Based on Class of Drug: ACE Inhibitors 28% p= RR (95% CI Random) Healey JS, et al. J Am Coll Cardiol (2005) 45: 1832

93 Study Treatment (n/N) Control (n/N) Weight (%) RR (95% CI Random) ARB Madrid9/7922/75 ValHeFT116/ /2200 Charm179/ /2749 LIFE179/ /4387 Sutotal (95% CI)483/ / (0.19, 0.79) (0.53, 0.84) (0.68, 1.00) (0.59, 0.85) (0.60, 0.84) Test for heterogeneity chi-square=5.25; df=3; p=0.15 Test for overall effect z=-4.12; p= Effect of Treatment Based on Class of Drug: ARBs 29% p= RR (95% CI Random) Healey JS, et al. J Am Coll Cardiol (2005) 45: 1832

94 Effect of ACE Inhibitors or ARB Based on Indication StudyTreatment (n/N)Control (n/N) Heart Failure Van Den Berg2/77/11 SOLVD10/18645/188 ValHeFT116/ /2300 Charm179/ /2749 Sutotal (95% CI)307/ /5148 Weight (%)RR (95% CI Random) (0.13, 1.57) (0.12, 0.43) (0.53, 0.84) (0.66, 1.00) (0.37, 0.85) Test for heterogeneity chi-square=15.01; df=3; p< Test for overall effect z=-2.72; p= % Hypertension CAPP117/ /5493 LIFE178/ /4387 STOP-H2200/ /4409 Sutotal (95% CI)496/ /14/ (0.69, 1.11) (0.59, 0.85) (0.95, 1.32) (0.65, 1.19) Test for heterogeneity chi-square=13.34; df=2; p= Test for overall effect z=-0.82; p=0.4 12% RR (95% CI Random) Healey JS, et al. J Am Coll Cardiol (2005) 45: 1832

95 Effect of ACE Inhibitors or ARB Based on Indication StudyTreatment (n/N)Control (n/N) Weight (%)RR (95% CI Random) Atrial Fibrillation Madrid9/7922/75 Ueng15/7032/75 Sutotal (95% CI)27/14954/ (0.19, 0.79) (0.37, 0.97) (0.35, 0.79) Test for heterogeneity chi-square=1.33; df=1; p=0.31 Test for overall effect z=-3.13; p= % Post-Myocardial Infarction TRACE22/79042/787 GISSI665/ /6646 Sutotal (95% CI)27/14954/ (0.31, 0.87) (0.83, 1.02) (0.43, 1.26) Test for heterogeneity chi-square=4.64; df=1; p=0.031 Test for overall effect z=-1.12; p=0.3 27% RR (95% CI Random) Healey JS, et al. J Am Coll Cardiol (2005) 45: 1832

96 Non-antiarrhythmic drugs Statins

97 Lozano HF, et al. Heart Rhythm (2005) 2: 1000 StudyDesign Medication and subjectsORComments Statin drugs in protecting against AFib Retrospective analysis of prospective study database Statin users vs nonusers in a population of chronic CAD (n=449) 0.48 (CI )Effect of statins was independent of changes in serum cholesterol. AFib diagnosed by ECG at routine follow-up visits or with new symptoms onset. Prevention of AFib recurrence after cardioversion Retrospective analysis of patients referred for cardioversion Statin users vs nonusers in a population with persistent lone AFib (n=62) 0.31 (CI )Patients on statins had higher cholesterol and were older than nonusers. AFib diagnosed by ECG at routine follow-up visits. Prevastatin to prevent recurrent AFib after electrical cardioversion Prospective, open-label, controlled multicenter study Pravastatin 40 mg/day vs no drug 3 weeks prior and 6 weeks cardioversion (n=114) 1.08 (CI not available) Open-label design, small study, conventional antiarrhythmics also used. 52% 69% 8% Studies of Statins to Prevent AFib

98 Effect of Atorvastatin on Reducing AFib Recurrence Post-ECV Ozaydin M, et al. Am J Cardiol (2006) 297: 1490 Freedom from recurrence Follow-up (days) Atorvastatin control patients with AFib lasting >48h and followed for 3m p=0.01

99 Non-antiarrhythmic drugs Polyunsaturated fatty acids (omega-3)

100 Polyunsaturated Fatty Acids in Preventing AFib Calò L, et al. J Am Coll Cardiol (2005) 45: Patients free of AFib (%) Control Group PUFAs Group Days after surgery Log-rank p=0.009

101 Mozzafarian D, et al. Circulation (2004) 110: 3683 AFib-Free Survival According to Fish Consumption Tuna or other broiled/baked fish Survival free of AFib p< (log-rank test for equality of survivor functions) 5+/wk Years /wk 1-3/mo <1/mo

102 AFib-Free Survival According to Fish Consumption Fried fish or fish sandwich Survival free of AFib p= (log-rank test for equality of survivor functions) <1/mo Years /mo 1+/wk Mozzafarian D, et al. Circulation (2004) 110: 3683

103 n-3 Fatty Acid Intake from Fish and Incidence of AFib Brouwer IA, et al. Am Heart J (2006) 151: 857 European population-based prospective cohort study among subjects aged 55 years and above (n=6808) Dietary intake data available from 5184 subjects without AFib – In the subsequent 6.4y follow-up period, 312 subjects developed AFib – Incidence of AFib was not significantly associated with either long-chain fatty acid consumption or fish consumption Rotterdam study

104 Treatment Options for AFib Drugs to Control Ventricular Rate

105 Permanent AFib and Ventricular Rate Control Indications for control of ventricular rate: Failure of antiarrhythmic therapy for preventing recurrence Alternative treatment to maintain sinus rhythm

106 n Clinical symptoms n ECG Criteria n Hemodynamic data l VR bpm At rest l VR bpm During moderate exercise Definitions and Criteria for Rate Control

107 Digoxin Calcium Antagonists Beta-Blockers Antiarrhythmic Drugs Drugs Used for Rate Control ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation J Am Coll Cardiol (2006) 48: 854

108 Rate Control Drugs in AFFIRM Digoxin 51% Beta-blockers 49% Calcium antagonists 41% AV node ablation 5%

109 Beasley R, et al. Br Med J (1985) 290: 9 Digoxin in Permanent AFib bpm Rest Moderate Strenuous p< Heart rate during physical exercise and at various plasma concentrations SR Nil Low High

110 Roth A, et al. Circulation 73: 316 Digoxin plus Diltiazem in Permanent AFib bpm RestSubmax Exercise Max Exercise *p<0.05 vs DG+DL *p<0.05 vs DL 360 °p<0.05 vs DG Medium and high doses alone or in combination with digoxin *° * * DG DG+DL 240 DL 240 DL 360

111 Gallopamil 100 mg b.i.d. Diltiazem 120 mg b.i.d. Verapamil 120 mg b.i.d. Digoxin 0.8 – 1.4 µg/ml Botto GL, et al. Clin Cardiol 21: 837 Study protocol (7 day administration of slow release formulation) Calcium Antagonists in Permanent AFib

112 bpm Median VRMinimum VR Maximum VR *p<0.001 o p<0.01 vs DGX Holter and walking test ° * * DGX GLL DLT VRP Botto GL, et al. Clin Cardiol 21: 837

113 DiBianco R, et al. Am Heart J (1984) 108: 1121 Nadolol for Control of Ventricular Rate Effect on heart rate in patients on digoxin bpm RestingLowAverage p< ’ ExerciseMax Exercise Nadolol median dose 87 mg DGX NDL

114 Atwood JE, et al. J Am Coll Cardiol (1987) 10: 314 Beta-blockers for Control of Ventricular Rate kg/min Effect of nadolol on physical exercise capacity Sec Exercise time O 2 Consumption p<0.01 DGX CLP DGX DLT DiBianco R, et al. Am Heart J (1984) 108: 1121

115 Metoprolol 200 mg/d Diltiazem 300 mg/d Digoxin 0.8 – 1.4 µg/ml Placebo Botto GL, et al. PACE (2000) 23: 649 Randomized, cross-over study with administration for 7-10 days Modulation of Ventricular Rate Study protocol

116 Modulation of Ventricular Rate Metres walked Walking test results Max heart rate * o *p<0.05 vs PLA e DGX o p<.,01 vs PLA e DGX *p<0.005 vs DGX o p<0.05 vs MTP * *o*o * DGX Placebo DLT MTP Botto GL, et al. PACE (2000) 23: 649

117 Antiarrhythmic Drugs for Control of Ventricular Rate Amiodarone Solatolol

118 CHF-STAT Study: Amiodarone in Permanent AFib Deedwania PC, et al. Circulation (1998) 98: 2574 bpm Baseline2 w6 m m NSp=0.001 p=0.006 Amiodarone (400 mg/d) Placebo

119 Treatment Options for AFib Drugs to Reduce Thromboembolic Risk

120 Atrial Fibrillation and Stroke Anticoagulant therapy is clearly indicated and beneficial in valvular atrial fibrillation. In non-valvular atrial fibrillation, major randomized trials have provided useful guidelines for identifying and treating patients at risk.

121 Major Clinical Trials of Primary Prevention in Non-Valvular AFib SPAF 1 Stroke Prevention in Atrial Fibrillation BAATAF 2 Boston Area Anticoagulation Trial for Atrial Fibrillation CAFA 3 Canadian Atrial Fibrillation Anticoagulation AFASAK 4 Copenhagen Investigators SPINAF 5 Stroke Prevention in Non-rheumatic Atrial Fibrillation 1 Lancet (1989) 1: N Engl J Med (1990) 323: J Am Coll Cardiol (1991) 18: Circulation (1991) 84: N Eng J Med (1992) 327: 1406

122 SPAFBAATAFCAFA AFASAKSPINAF Number of Patients Drug UsedWarfarinASAWarfarinWarfarinWarfarinASAWarfarin (INR 2-4.5)325 mg(PT x(INR 2-3)(INR )75 mg(INR ) Control) Embolic Rate (%) Treatment2,33,60,413,51,56,04,3 Control7,46,32,985,26,26,20,9 Risk Reduction (%) (95% confidence) —79 Major Bleeding Complications (%) Treatment Control Major Clinical Trials of Primary Prevention in Non-Valvular AFib

123 100%50%0%-100%-50% All Risk reduction Warfarin better Warfarin worse SPINAF SPAF CAFA BAATAF AFASAK EventsPts/y Adjusted Dose Warfarin vs Placebo

124 Atrial Fibrillation Investigators Arch Intern Med (1994) 154: Control Warfarin Annual risk of stroke (%) 1.4% 4 4.5% Reduction in risk = 68% Reduction in Stroke Risk – Meta- analysis of 5 Trials

125 Average - 68% Study Range INR Stroke risk reduction EAFT 2.5 – % 1007 patients > 70 with previous TIA or minor stroke European Atrial Fibrillation Trial Lancet (1993) 342: 1255 vs placebo Secondary Prevention

126 Primary prevention AFASAK 75 mg - 18% (ns) SPAF 325 mg - 44% (p<0.02) Secondary prevention EAFT 300 mg - 14% (ns) Global reduction in risk = 25% (range 14-44%) Aspirin vs Placebo Study ASA dose Stroke risk reduction

127 Warfarin Superior to Aspirin AFASAK I (1) AFASAK II (2) EAFT (9) PATAF (15) SPAF II (4) All trials (n=5) Relative Risk Reduction (95% CI) Warfarin better (%) Warfarin worse (%) Warfarin compared with aspirin AFASAK I (1) SPAF I (3) EAFT (9) ESPS II (14) LASAF (13) UK-TIA (16) All trials (n=6) Relative Risk Reduction (95% CI) Aspirin better (%) Aspirin worse (%) Aspirin compared with placebo ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation J Am Coll Cardiol (2006) 48: 854

128 SPAF Investigators Lancet (1994) 343: 634 Discontinued = 31 Lost to follow-up = 0 Primary events = 11 Deaths = 34 Completed without primary event = eligible patients randomised Fixed, low dose warfarin plus aspirin (n = 521) INR assessed at 1m and 2m then every 3m Discontinued = 41 Lost to follow-up = 0 Primary events = 44 Deaths = 35 Completed without primary event = 442 Adjusted dose warfarin (n = 523) Weekly INR control until stable, then monthly SPAF III - Adjusted-dose vs. Low- intensity, Fixed-dose warfarin + ASA

129 SPAF Investigators Lancet (1996) 348: 633 Combination therapy Adjusted-dose warfarin Cumulative event rate (% per year) Days from randomization Combination therapy Warfarin therapy Number at Risk SPAF III – Stroke Rate

130 Major haemorrhage Adjusted dose warfarin better Stroke, MI, Vascular death All disabling strokes Disabling ischaemic stroke Primary events Combination therapy better SPAF Investigators Lancet (1996) 348: 633 SPAF III – Relative Risk

131 AFASAK 2 - Copenhagen Investigators 677 patients with permanent AFib Warfarin fixed-dose 1.25 mg Warfarin fixed-dose 1.25 mg + ASA 300 mg ASA 300 mgWarfarin dose variable (INR ) Cumulative incidence of primary events – 12m follow-up 5.8 % 7.2 % 3.6 % 2.8 %

132 SPAF III (adjusted) INR range ( ) recommended by 4 th ACCP Consensus on Antithrombotic Therapy EAFT SPINAF CAFA BAATAF AFASAK Warfarin – INR range SPAF I + II SPAF III (fixed) Primary Prevention Trials – Anticoagulation Ranges

133 2INR3 Clinical events ThromboembolicHaemorrhagic Therapeutic window Optimal Anticoagulation Ranges

134 Connolly SJ, et al. J Am Coll Cardiol (1991) 18: 349 Ezekowitz MD, et al. N Engl J Med (1992) 327: 1406 SPAF II Lancet (1994) 343: 687 Connolly SJ, et al. Lancet (1994) 343: 1509 Petersen P, et al. Lancet (1989) 171 SPAF Circulation (1991) 84: 527 BAATAF N Engl J Med (1990) 323: 1505 EAFT Lancet (1993) 342: Median age (y) 2 1 Intracranial haemorrhage (%/y) 80 Oral anticoagulant Aspirin SPAF II (>75) SPINAF (>70) 4 trials (>75) AFASAKEAFT BAATAF SPINAF CAFA SPAF I SPAF II (<75) Intracranial Haemorrhage in Trials – Influence of Age

135 Treatment Options for AFib Drugs to Reduce Thromboembolic Risk Risk stratification

136  Clinical risk factors  Echocardiographic risk factors Thromboembolic Risk Stratification

137  Advanced age (> women)  Hypertension  Cardiac insufficiency  Previous TIA  (Diabetes) Clinical Risk Factors

138  Left atrial dilatation  Left ventricular systolic dysfunction Transthoracic Echocardiographic Risk Factors

139  Thrombus – atrium and/or left atrial appendage  Dense spontaneous echo contrast  Reduced blood flow in left atrial appendage  Dilatation of left atrial appendage  Septal aneurysm  Complex aortic plaque Trans Esophageal Echocardiographic Risk Factors

140 HIGH RISKMODERATE RISKLOW RISK 1 major risk factorNO major risk factorNo major or > 1 moderate risk factor 1 moderate risk factorminor risk factors Major Risk Factors Age > 75 Previous stroke or systemic embolism History of arterial hypertension Cardiac insufficiency o ventricular dysfunction Mitral valve disease Prosthetic valve replacement Minor Risk Factors Age Diabetes mellitus Ischaemic cardiopathy with normal ventricular function sinistra adapted from the 6th ACCP Consensus Conference on Antithrombotic Therapy, Chest (2001) 119 (Suppl): 194S Risk Stratification in Patients with AFib

141 Antithrombotic Therapy Recommendations Female gender Age greater than or equal to 75 y Previous stroke, TIA or embolism Age 65 to 74 yHypertensionMitral stenosis Coronary artery diseaseHeart failureProsthetic heart valve * Thyrotoxicosis LV ejection fraction 35% or less Diabetes mellitus Moderate-risk factors Less validated or weaker Risk factors *If mechanical valve, target international normalized ratio (INR) greater than 2.5. INR = international normalized ratio; LV = left ventricular; TIA = transient ischemic attack High-risk factors No risk factorsAspirin, 81 to 325 mg daily One moderate-risk factor Aspirin, 81 to 325 mg daily, or warfarin (INR 2.0 to 3.0, target 2.5) Any high-risk factor or more than 1 moderate-risk factor Warfarin (INR 2.0 to 3.0, target 2.5) * Risk categoryRecommended therapy

142 Contraindications of Oral Anticoagulants GI haemorrhage Uncontrolled arterial hypertension Pregnancy Alcoholism Severe hepatic insufficiency Vascular malformations that can lead to risk of haemorrhage Coagulopathies Recent surgical interventions – eyes or CNS Previous severe haemorrhage during anticoagulation therapy Severe neoplastic disease

143 Cardioversion and Anticoagulation Recommendations Naccarelli GV, et al. Am J Cardiol (2000) 85: 36D Cardioversion Heparin + warfarin 24 h Warfarin (INR ) 3-4 weeks + Cardioversion NegativePositive Warfarin 3-4 weeks TEE AFib > 48 hours

144 Treatment Options for AFib Non-Pharmacologic Treatment Options

145 SurgeryElectrophysiologicalDevices Pacemaker (single or dual chamber) Internal atrial defibrillators Catheter ablation AV node ablation Non-Pharmacological Treatment Options for AFib Maze procedure Modified Maze (mini-Maze) ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation J Am Coll Cardiol (2006) 48: 854

146 Management of AFib - Summary Maintenance of sinus rhythm should be the primary objective of treatment whenever possible – sinus rhythm correlates with improved survival Current antiarrhythmic drug therapies, however, are not highly effective in maintaining SR and generally have poor outcomes – high recurrence rates – adverse effects and high discontinuation rate A potentially curative therapy for AFib is desirable


Download ppt "Section II: Clinical Management of AFib. Section II. Clinical Management of AFib 1. Clinical Evaluation of AFib 2. Treatment Options for AFib Cardioversion."

Similar presentations


Ads by Google