Management of atrial fibrillation a holistic view - Prof. Dr. Martin Borggrefe Mannheim

Transcription

1 a holistic view - Prof. Dr. Martin Borggrefe Mannheim

2 Patients with atrial fibrillation (millions) Management of atrial fibrillation Expected prevalence of apparent AF 5,1 5,1 5,9 5,6 6,7 6,1 2,08 2,26 2,44 2,66 7,7 6,8 2,94 8,9 7,5 3,33 10,2 8,4 3,8 11,7 9,4 4,34 13,1 10,3 4,78 14,3 11,1 5,16 15,2 15,9 12,1 11,7 Mayo Clinic data (assuming no further increase in the AF incidence) 1,2 5,42 5, Year 1. Miyasaka Y et al. Circulation 114: (2006) 2. Savelieva I, Camm J. Clin Cardiol 31:55 62 (2008) 3. Go AS et al. JAMA 285: (2001) Mayo Clinic data (assuming a continued increase in the AF incidence) 1,2 ATRIA study data 2,3

3 Burden of disease : AF The Framingham Heart Study mortality curves for subjects 55 to 74 years of age (n=159) (n=133) (n=318) (n=266) Benjamin et al, Circulation 1998;98:

4 Death in AF Annual death rates 1.5-4% in controlled trials Death rate is highest in the 1st year after diagnosis No individual treatment of AF has been shown to reduce mortality - Anticoagulation improves survival in meta analyses - Successful rhythm control (sinus rhythm) is associated with better survival - Rhythm control therapy per se does not affect survival Death may be - due to AF, - a side effect of therapy, bleeds proarrhythmia periprocedural complications, - unrelated to AF Benjamin et al. Circulation 1998: Corley et al. Circulation 2004;109: Lip, Edwards, Thromb Res. 2006; 118:

5 15% Aetiology of ischemic stroke Artery occlusion % atherothrombotic % cardioembolic 15-20% lacunar 5-10 % infrequent 25 % cryptogenic

6 Stroke severity in AF (Framingham) Lin et al, Stroke 1996; 27:

7 Stroke risk in paroxysmal / sustained AF ACTIVE W subanalysis, 526 centers, 15 countries 6706 patients, 3371 on OAC (warfarin), 3335 clopidogrel + aspirin (warfarin better) Cumulative hazard rates of stroke and non-central nervous systemic embolisms Hohnloser et al. J Am Coll Cardiol 50: (2007)

8 predicted mean of cognitive performance (z-score, 95% CI) Strokes in AF - the tip of the iceberg? 20% of all strokes severe strokes Reduced cognitive performance in AF patients 0,50 0,25 0,00-0,25-0,50-0,75 Visuo-spatial abilities (NS) Working memory (NS) Executive functions (NS) Cognitive domains Learning and memory (p=0.01) Knecht et al. Eur Heart J 2008; 29, patients with AF without stroke 563 control subjects

9 Why do we treat AF? 1. Death 2. Stroke and cerebral bleeds 3. Quality of life 4. Rhythm 5. Left ventricular function 6. Health economics 7. Additional important outcome variables: cardiovascular complications, e.g. acute coronary syndrome or decompensated heart failure 2nd AFNET/EHRA consensus document. Kirchhof P, et al. Europace/EurHJ 2009 (June 17th 2009)

10 Why do we treat AF? 8. Silent stroke (including asymptomatic intracerebral bleeds) and cognitive function 9. Social functioning and disease-related quality of life 10. Progression to more sustained forms of AF 11. Left ventricular function 12. Left atrial function 2nd AFNET/EHRA consensus document. Kirchhof P, et al. Europace/EurHJ 2009 (June 17th 2009)

11 The "ECG focused" approach Rhythm control Time to first recurrence of AF Number of recurrences over time Recurrences identified by: Routine ECGs/symptomatic ECGs Prolonged monitoring: event recorders, automated recorders Rate control Ventricular rate in AF (ECG, Holter, GXT) Outcomes in AF, Oct (2)

12 Major Trials Comparing Rhythm Strategy and Rate Strategy Major trials include: AFFIRM RACE PIAF, STAF, HOT CAFE AF-CHF Major overall findings: Rhythm-control strategy was not superior to rate-control strategy in terms of morbidity/mortality Appropriate choice of therapy should be based on each patient s symptoms and disease Comprehensive management of patients with AF can involve rate control, prevention of thromboembolism, and correction of the rhythm disturbance - these strategies are not mutually exclusive 1. The AFFIRM Investigators. N Engl J Med. 2002;347: ; 2. Van Gelder IC, et al. N Engl J Med. 2002;347: ; 3. Hohnloser SH, et al. Lancet. 2000;356: ; 4. Carlsson J, et al. J Am Coll Cardiol. 2003;41: ; 5. Opolski G, et al. Chest. 2004;126: ; 6. Roy D, et al. N Engl J Med. 2008;358: ; 7. Fuster V, et al. Circulation. 2006;114:e257-e354.

13 Mortality (% patients) Event-free survival (%) AFFIRM and RACE: Main Results AFFIRM All-cause death 27% vs 26% (P = ) RACE Death, CVA/TIA, hospitalization -5.4% 90% CI(-11%, 0.4%) % Rate control Rhythm control Rate control % Rhythm control Years Years

14 What is Adequate Rate Control? Beats per minute < 110 < 110 < < 100 < 80 < Concerns Definition of heart rate control based on benefits from short term hemodynamic studies Not well studied with regards to regularity vs irregularity No standardised method of assessment 0 AFFIRM Rest Mild exercise RACE RACE 2 strict RACE 2 lenient Guidelines Proposal bpm at rest to 115 bpm during moderate exercise ACC/AHA/ESC Guidelines. Eur Heart J. 2006;27:

15 McNamara RL et al., Ann Intern Med 139: (2003) Management of atrial fibrillation Most ion channel blockers double SR rate

16 Amiodarone prevents recurrent AF better than sotalol or propafenone Roy D, et al. N Engl J Med.342: (2000) Singh BN, et al. N Engl J Med.352: (2005)

17 How can we improve AA drug therapy? Identify patients at risk for proarrhythmia Shortening of therapy duration New (multi channel inhibitor) drugs

18 How can we improve AA drug therapy? Identify patients at risk for proarrhythmia Shortening of therapy duration New (multi channel inhibitor) drugs

19 abnormal QT prolongation (K + blocker) abnormal QRS prolongation (Na + blocker) > 0,06s QT-prolongation or QT > 0,5s > 25% QRS increase during initiation of antiarrhythmic drug therapy are clear indicators for a risk of proarrhythmia modified from Kirchhof P, et al. Heart.92: (2006)

20 How can we improve AA drug therapy? Identify patients at risk for proarrhythmia Shortening of therapy duration New (multi channel inhibitor) drugs

21 pill in the pocket : Convert AF at home 210 patients enrolled - flecainide effective in hospital 165 patients with recurrences (79%) 569 / 618 treated episodes (92%) 534 / 569 conversion to SR (94%) - outpatient single dose 300 / 200 mg flecainide 600 / 450 mg propafenone Alboni et al, NEJM 351: (2004)

22 Comprehensive management of AF AF requires therapy of all ist causes often multimodal therapy of different factors may prevent progression of AF Adequate anticoagulation will prevent strokes and potentially cognitive decline Better treatment of concomitant conditions Hypertension, diabetes, vascular disease, structural heart disease, LV failure, smoking may prevent AF-related complications and potentially maintain SR Early, comprehensive rhythm control therapy may allow to stabilize rhythm and to prevent AF-related complications may allow to maintain SR and to prevent AF-related complications 2 nd AFNET/EHRA consensus document, Kirchhof P, et al. Eur Heart J.30: c (2009)

23 AF Increases Risk Along the Cardiovascular Continuum Remodelling Ventricular dilation MI Heart failure Atherosclerosis and LVH Risk factors (diabetes, hypertension) Atrial fibrillation 1,2 End-stage microvascular and heart disease Death 1. Benjamin EJ, et al. JAMA. 1994;271: ; 2. Krahn AD, et al. Am J Med. 1995;98: ; 3. Nakashima H, et al. Circulation. 2000;101: ; 4. Tsai CT, et al. Circulation. 2004;109:

24 Camm et al. Eur Heart 2012; 33:

25 Risk factor CHA2DS2-VASc-Score C Congestive heart failure /LV dysfunction 1 H Hypertension 1 A2 Age 75 2 D Diabetes mellitus 1 S2 Stroke / TIA / thrombo-emoblism 2 V Vascular disease 1 A Age S Sex category (i.e. female sex) 1 Maximum score 9 Score

26 Stroke risk CHA 2 DS 2 -VASC

27 Indications for oral anticoagulant Camm et al. Eur Heart J 2012; 33;

28 Clinical trials involving novel anticoagulants vs. warfarin for stroke prevention in non-valvular AF - 1 Camm et al. Eur Heart 2012; 33:

29 Clinical trials involving novel anticoagulants vs. warfarin for stroke prevention in non-valvular AF - 2 Camm et al. Eur Heart 2012; 33:

30 N Engl J Med 2011; 365:883-91

31 Cumulative Rates of the Primary End Point (Stroke or Systemic Embolism) in the Per-Protocol Population Patel et al, N Engl J Med 2011; 365:883-91

32 % pro Jahr Primary endpoint [ITT-Analysis] [Stroke or systemic embolism] % pro Jahr RE-LY (gesamt) RE-LY (CHADS 3-6) * ROCKET-AF 3 RR 0,79 (95 % KI: 0,59 1,06)** RR 0,70 (95 % KI: 0,52 0,95)*** 3 RR 0,88 (95 % KI: 0,74 1,03) p=0, ,68 RR 0,90 (95 % KI: 0,74 1,10) 2,42 2 p=0,30 + RR 0,65 (95 % KI: 0,52 0,81) 2,12 2 2,12 p<0, ,71 1,88 1,54 1 1, D110 mg D150 mg Warfarin D110 mg D150 mg Warfarin Rivaroxaban Warfarin 0 Mahaffey ; Oral presentation at AHA, 15th November 2010; Connolly et al. N Eng J Med 2009; 361: ; Connolly et al. N Eng J Med 2010; 363: ; Oldgren et al. J Am Coll Cardiol 2010; 55: A1.E2; Oldgren J. Oral presentation at ACC, Atlanta, Mar 15th 2010

33 Lancet 2014; 383:955-62

34 Meta-analysis of RE-LY, ROCKET AF, ARISTOTLE, and Engage AF-TIMI Stroke or systemic embolic events Ruff et al. Lancet 2014; 383:955-62

35 Meta-analysis of RE-LY, ROCKET AF, ARISTOTLE, and Engage AF-TIMI Secondary efficacy and safety outcomes Ruff et al. Lancet 2014; 383:955-62

36 Meta-analysis of RE-LY, ROCKET AF, ARISTOTLE, and Engage AF-TIMI Major bleeding Ruff et al. Lancet 2014; 383:955-62

37 May Jun Jul Aug Sep Oct Nov Dec Jan 11 Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec Jan 12 Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec Jan 13 Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec Jan 14 Feb Mar Sales EUR DOACs Sales Nov 2013: Rivaroxaban 29 Mio, Dabigatran 8 Mio, Apixaban 2.4 Mio Sales DOACs ( ) RIVAROXABAN DABIGATRAN ETEXILATE APIXABAN

38 N Engl J Med 2012;366:120-9.

39 Risk of ischemic stroke or systemic embolism Healey et al. N Engl J Med 2012;366:120-9

40 Screening of AF Camm et al. Eur Heart 2012; 33:

41 Catheter Ablation and Atrial Fibrillation Peters et al. Lancet 2002; 359:

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44 Ablation versus Antiarrhythmic therapy: Randomized Trials Tung et al. Circulation 2012; 126:

45 Catheter Ablation and Atrial Fibrillation AF ablation: what do we know in 2015? Catheter ablation can effectively eliminate paroxysmal AF. The most successful treatment strategy is circumferential and complete PV-isolation. The complication rate of radiofrequency catheter ablation of atrial fibrillation is 4%, ablation-associated mortality is low.

46 Circ Arrhythm Electrophysiol 2013; 6:

47 Complications of AF Ablation Major complications No. of studies % pooled complication rate (95% CI) I² statistic Acute complication rate ( ) 83.8 Type of complication Death ( ) 0.0 Atrioesophageal fistula ( ) 0.0 Pulmonary vein stenosis ( ) 79.6 Vascular complications ( ) 94.1 Arteriovenous fistula ( ) 45.5 Femoral pseudoaneurysm ( ) 41.2 Stroke/TIA ( ) 46.8 Stroke ( ) 34.3 TIA ( ) 37.9 Tamponade ( ) 68.5 Pericardial effusion ( ) 55.0 Phrenic nerve injury ( ) 70.2 Diaphragmatic paralysis ( ) 0.0 DVT/PE ( ) 0.0 Pneumothorax ( ) 0.0 Hemothorax ( ) 0.0 Gupta et al. Circ Arrhythm Electrophysiol 2013; 6: Sepsis, abscesses, or endocarditis ( ) 0.0 Valve damage ( ) 0.0 Gupta et al. Circ Arrhythm Electrophysiol 2013; 6:

48 Ablation strategy description Complications of AF Ablation Ablation strategy No. of studies % pooled complication rate (95% CI) P Value I² statistic 1 PVI alone ( ) PVA ablation/pvai ( ) Linear substrate ( ) CEAE alone ( ) CFAE as adjunct ( ) Tailored ( ) Stepwise ( ) Gupta et al. Circ Arrhythm Electrophysiol 2013; 6:

49 Electrical and structural remodelling Management of atrial fibrillation Catheter Ablation and Atrial Fibrillation Is AF ablation curative? Atrial fibrillation as progressive atrial cardiomyopathy Time

50 Electrical and structural remodelling Management of atrial fibrillation Catheter Ablation and Atrial Fibrillation When is the right time for ablation? Atrial fibrillation as progressive atrial cardiomyopathy Time

51 Circulation 2010; 122:

52 Paroxysmal Atrial Fibrillation Kaplan-Meier analysis of longterm freedom from recurrent ATas after the initial procedure (A) and after the last ablation procedure with a median of 1 (1 to 3) ablation procedure (B). Ouyang et al. Circulation 2010; 122:

53 Catheter Ablation and Atrial Fibrillation Impact of mega-trials on the future of AF ablation