surrey cardiology conference 2014 - st peter's hospital · surrey cardiology conference 2014...

1

N5-319 Cumm Presentation

9/25/2014 3:38 PM

Surrey Cardiology Conference 2014Latest Therapies in the Management of Atrial Fibril lation

Royal Holloway University of London

Medication vs. Ablation in AFWhich When

and Why?

A. John CammSt. George’s University of London

and Imperial College, LondonUnited Kingdom

A

Declaration of InterestsChairman: NICE Guidelines on AF, 2006; ESC Guidelines on Atri al Fibrillation ,2010 and Update, 2012; ACC/AHA/ESC Guidelines on VAs and SCD; 2006; NICE Guidelines on ACS and NSTEMI, 2012; NICE Guidelines on heart f ailure, 2008; NICE Guidelines on Atrial Fibrillation, 2006; ESC VA and SCD Guidel ines, 2015

Steering Committees: multiple trials including novel anticoagulants

DSMBs: multiple trials including BEAUTIFUL, SHIFT, SIGNFIG Y, AVERROES, CASTLE-AF, ASTAR II, INOVATE, and others

Events Committees: one trial of novel oral anticoagulants and multiple trials of miscellaneous agents with CV adverse effects

Editorial Role: Editor-in-Chief, EP-Europace and Clinical Cardiolog y; Editor, European Textbook of Cardiology, European Heart Jou rnal, Electrophysiology of the Heart, and Evidence Based Cardiology

Consultant/Advisor/Speaker: Astellas, Astra Zeneca, ChanRX, Gilead, Merck, Menarini, Otsuka, Sanofi, Servier, Xention, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Pfizer, Boston Scient ific, Biotronik, Medtronic, St. Jude Medical, Actelion, GlaxoSmithKline, InfoBionic , Incarda, Johnson and Johnson, Mitsubishi, Novartis, Takeda

2


9/25/2014 3:38 PM

Antiarrhythmic Medical Therapies

Upstream therapies

Antiarrhythmic AgentsNew and Old

Amiodarone

Sotalol

ClassIII

Propafenone

Flecainide

ClassIc

Nexteroneand

Budio-darone

Multi-channel blockers

Class Ia: Disopyramide, Quinidine and ProcainamideClass 1b: mexiletine, tocainide

Modified from Savelieva I and Camm AJ. Europace 2008 :10:647–65

Beta blocker

IKAChBlocker

ConnexinModulator

Late Na blockers

SAC Blockers

IKur Blockers

Na+/Ca2+Inhibitor

Na+/H+ Inhibitor

Ryanodine ReceptorModulator

IK1 Blockers

Novel Drugs

Anti inflammatory

New Class III Agents

Azimilide

Dronedarone

Celivarone

Vernakalant

Tedisamil

Dofetilide

Vanoxerine Abandoned

Abandoned

AbandonedUSA only

Chloroquine Xen 0103

Ranolazine

NTC-801

RotigaptideDangaptide

Colchicine

1.0

0.9

0.8

0.7

0.6

0.5

0.4

0.3

0.2

0.1

SAFE-T Sotalol Amiodarone AF Efficacy Trial

Singh BN et al. NEJM. 2005;352:1861-1872.

• VA Cooperative Study,

• N=665, 20% AF >1 year:

• Amio 267, Sot 261, Placebo 137

Sotalol

Placebo

Amiodarone

Days

Fre

e fr

om

AF

rec

urr

ence

(O

T /

ITT

)

• Follow-up 1year with TTM,

• 1o EP: time to 1st AF recn after CV

0

20

40

60

80

Spontaneous DCC Failed CV Total

Co

nve

rsio

n to

SR

[%

]

AmiodaroneSotalolPlacebo

300 10009008007006005004002001000

3


9/25/2014 3:38 PM

100100

8080

6060

4040

2020

00

Time (days)Time (days)

% sinus rhythm% sinus rhythm

60060050050040040030030020020010010000

Probability of remainingin sinus rhythm (N = 403)CTAF

Sotalol

Propafenone

39%

Amiodarone69%

Open labelFollow-up from Day 21

Amiodarone Prevents AF in SCD-HeFT

Singh BN, et al. Am Heart J 2006;152:e7-11

SCD-HeFT

SR n = 2328

AF n = 173

ICD 757 (33%) 65 (38%)

Amiod-arone

771 (33%) 64 (37%)

Placebo 800 (34%) 44 (25%)

New AF 264 (11%) -

Proportion with new AF

0.20

0.15

0

0.05

0.1

0.15

0.2

0.25

0 1 2 3 4 5Years

ICDPlaceboAmiodarone

0.12

ICD: Placebo 1.33 (0.97 – 1.82) 0.044ICD: Amio 1.96 (1.37 – 2.82) 0.001Amio: Placebo 0.68 (0.47 – 0.98) 0.019

4


9/25/2014 3:38 PM

Museum of Modern Art

Cornedbeef®200200 mg Amiodarone Hydrochloride Fr. P.

28 TabletsDamienDamienDamienDamien

Hirst H

'I can't understand why some people believe completely in medicine and not in art, without questioning either' (quoted in Damien Hirst). The Last Supper refers to the way in which medicinal drugs are becoming a regular part of everyday life, as common as the food.

Class IA < 0.001Class IC < 0.001Metoprolol

Class III < 0.001Amiodarone < 0.001Dofetilide < 0.001Sotalol < 0.001

Quinidine vs. class IQuinidine vs. sotalolAmiodarone vs. class I < 0.001Amiodarone vs. sotalol < 0.001Sotalol vs. class I

0 0.5 1 1.5 2

AF Recurrence

Odds ratio (95% CI)

Lafuente-Lafuente C, et al. Cochrane Database Syst Rev. 2007;(4):CD005049.

AADs for Prevention of AF After DCCSystematic Review of RCTs

RCTs included in analysis

Total 44

No. of patients 11,322

Placebo controlled

25

Active comparator

14

Persistent AF 38 (60% pts)

PAF/recent onset 6

EF > 50% 41

Lone AF 1

Follow-up 1 year

5


9/25/2014 3:38 PM

Lafuente-Lafuente C, et al, Arch Intern Med 2006;166:719-28 Odds Ratio (95% CI)

Class IAClass ICMetoprololClass III

AmioDofetilideSotalol

Q vs Class IQ vs SotalolAmio vs Class IAmio vs SotalolSotalol vs Class I

0 1 2 3 4 5 6

0.04

0.009

Overall Mortality

Systematic Review of RCTsAADs for Mortality Reduction after DCC

AF Recurrence and All Cause MortalityOdds Ratios compared with Placebo

0.1 0.2 0.50.1 0.2 0.50.1 0.2 0.5 1 2 5 10 100

Dronedarone N=3378 0.85 (0.67 to 1.09) p=0.165

Amiodarone N=653 2.73 (1.00 to 7.41) p=0.049

Sotalol N=873 4.32 (1.59 to 11.70) p=0.013

0.53 (0.40, 0.72, p=0.0002)Dronedarone N=1131 0.53 (0.40, 0.72, p=0.0002)

0.36 (0.28, 0.48, p<0.0001)Propafenone N=1228 0.36 (0.28, 0.48, p<0.0001)

0.22 (0.16, 0.29, p<0.0001)Amiodarone N=978 0.22 (0.16, 0.29, p<0.0001)

0.40 (0.31, 0.52, p<0.0001)Sotalol N=1404 0.40 (0.31, 0.52, p<0.0001)

0.31 (0.19, 0.49, p<0.0001)Flecainide N=305 0.31 (0.19, 0.49, p<0.0001)

Antiarrhythmic Efficacy

All Cause Mortality

Freemantle N, et al. Europace 2011;13:329-45

6


9/25/2014 3:38 PM

ESC Recommendation Class Level

The following antiarrhythmic drugs are recommended for rhythm control in patients with AF, depending on underlying heart disease: • amiodarone• dronedarone• flecainide• propafenone• d.l-sotalol

IIIII

AAAAA

ESC AF GuidelinesAntiarrhythmic Medication for Rhythm Control

Camm J et al. Eur Heart J 2010;31:2369–429

Choice of Oral Antiarrhythmic Drug

Treatment of underlying condition and prevention of remodelling – ACE-I / ARB / statin

HFCHD

Significant structural heart diseaseMinimal or no structural heart disease

HHD

amiodarone

LVHNo LVH

amiodarone

dronedarone / flecainide / propafenone / sotalol

dronedarone

amiodarone

dronedarone

sotalol

European Heart Journal 2012 - doi:10.1093/eurheartj/ ehs253

7


9/25/2014 3:38 PM

Improving AAD Safety: Flec-SL Study

Kirchhof P, et al. Lancet 2012;DOI:10.1016/S0140-67 36(12)60570-4

ESC Recommendation

Class Level

Short-term (4 weeks) antiarrhythmic therapy after cardioversion may be considered in selected patients

IIb B

• N = 635, mean age 64 years, 67% hypertension • Flecainide 4 weeks vs long-term• 1o EP: time to persistent AF (telemetry) or death

0

0.2

0.4

0.6

0.8

1

0 50 100 150 200

Months

Pro

baab

ility

eve

nt-f

ree

ControlLong-term RxShort-term Rx

Observational Trials of AF AblationObservational Trials of AF Ablation

59 59.564

69 70 72 7378 80

83 85

77

0

20

40

60

80

100

Free from recurrent AF, %

N= ~2000 Follow-up 6 - 30 months

Pappone C, et al, JACC 2003;42:185-197

0 180 360 540 720 900 10800

20

40

60

80

100

Free from atrial fibrillation, %

Follow-up, days

Hazard ratio 0.30 (95% CI 0.24-0.37)p < 0.001

AAD

Ablation

• Non-randomised• 1171 consecutive pts

(ablation 589)

8


9/25/2014 3:38 PM

Treatment of AF: AADs and RFA Systematic Review

Calkins H, et al. Circ Arrhythmia Electrophysiol 20 09;2:349-61

• Studies between 1990 – 2007• Size of the studies ≥ 40 pts• Follow-up ≥ 30 days for AADs and ≥ 7 days

for RFA

Baseline characteristics RFA AAD

# studies (pts) 63 (8789) 34 (6589)

Age, years 55.5 61.6

AF duration, yrs 6.0 3.1

PAF, % 69.8 56.4

PersAF, % 14.9 35.1

AAD failure 2.6 1.7

LVEF, % 57.7 49.0

LA size, mm 41.6 43.7

SHD, % 30.6 49.5

IHD, % 10.0 18.2

CHF, % 15.7 24.6

Prior CABG, % 0 41.6%

Diabetes, % 4.8 12.1

HTN, % 30.3 38.420.0 40.0 60.0 80.0

Efficacy (95% CI), %

Placebo in AAD trials

AAD trials

Single RFA off AAF

Multiple RFA off AAD

Single RFA on AAD

Multiple RFA on AAD

Study # Pts Type of AF Pre AAD

AF free at 1 year

Ablation AAD

Krittayaphong, et al. 2003 30 Paroxysmal,

persistent ≥≥≥≥1 79% 40%

Wazni, et al. 2005, (RAAFT) 70 Mainly

paroxysmal No 87% 37%

Stabile, et al. 2005 (CACAF) 137 Paroxysmal,

persistent ≥≥≥≥2 56% 9%

Oral, et al. 2006 146 Persistent ≥≥≥≥1 74% 4%

Pappone, et al. 2006 (APAF) 198 Paroxysmal ≥≥≥≥2 86% 22%

Jais, et al. 2008, (A4 study) 112 Paroxysmal ≥≥≥≥1 89% 23%

Forleo, et al. 2008 70† Paroxysmal, persistent ≥≥≥≥1 80% 43%

Wilber, et al. 2009 (Thermocool) 167 Paroxysmal ≥≥≥≥1 66% 16%

Packer, et al.2010, (STOP-AF) 245 Paroxysmal ≥≥≥≥1 69.9% 7.3%

Modified from Camm J, et al. Nat Rev Cardiol 2009;6: 332-4

Fre

edo

m f

rom

AF

rec

urr

ence

[%

]

p<0.00166

16

0

20

40

60

80

100

PVI AAD

ThermocoolN = 167

AF Ablation or Antiarrhythmic Drugs?

9


9/25/2014 3:38 PM

RCTs of Ablation Versus AADs in AFRCTs of Ablation Versus AADs in AF

Nair GM, et all. JCE 2008

Thai study 0.333 0.112 0.995 0.049

RAAFT 0.204 0.078 0.531 0.001

CACAF 0.483 0.366 0.638 0.000

APAF 0.187 0.113 0.307 0.000

A4 0.258 0.151 0.415 0.000

Morady 0.618 0.387 0.987 0.044

Total 0.331 0.217 0.505 0.000

0.1 0.2 0.5 1.0 2.0

“Inclusion of case series can increase the evidence base and strengthen the credibility of a review of an emerging health technology”

Chambers D, et al. J Clin Epidemiol 2009

ThermoCool AF Trial

Catheter ablation –– Antiarrhythmic drug

HR, 0.3095% CI, 0.19 – 0.47Log-rank P < 0 .001

Follow-up (months)1 2 3 4 5 6 7 8 90

Symptomaticatrial arrhythmia

1.00

0.80

0.60

0.40

0.20

0

Fre

edo

m fr

om

sym

pto

mat

ic a

tria

l arr

hyt

hm

ia

Follow-up (months)1 2 3 4 5 6 7 8 90

Protocol-definedtreatment failure

0

1.00

0.80

0.60

0.40

0.20

Fre

edo

m fr

om

pro

toco

l-d

efin

ed tr

eatm

ent f

ailu

re

HR, 0.2495% CI, 0.15 – 0.39Log-rank P < 0 .001

Follow-up (months)1 2 3 4 5 6 7 8 90

Any atrial arrhythmia1.00

0.80

0.60

0.40

0.20

0

Fre

edo

m fr

om

any

atri

al a

rrh

yth

mia

HR, 0.2995% CI, 0.18 – 0.45Log-rank P < 0 .001

Wilber DJ, et al. JAMA. 2010;303:333-340.

10


9/25/2014 3:38 PM

Quality of Life (SF–36)ThermoCool AF

Catheter ablation AAD therapy

3-month 9-month6-month

Mental component summary (MCS)Mean absolute change from baseline

6

8

4

2

0

10

Ch

ang

e (u

nit

s)

6

4

2

0

8

3-month 9-month6-month

Physical component summary (PCS)Mean absolute change from baseline

Ch

ang

e (u

nit

s)

P < 0.001n = 90

P < 0.001n = 91

P < 0.001n = 91

P = 0.23n = 39

P = 0.77n = 20

P = 0.61n = 17

P < 0.001n = 90 P < 0.001

n = 91

P < 0.001n = 91

P = 0.69n = 39

P = 0.53n = 20 P = 0.92

n = 17

Baseline values for both groups similar, and below population norm of 50 (3 – 5 unit change considered clinically relevant)

Wilber DJ, et al. JAMA . 2010;303:333-340.

Primary Effectiveness Analysis STOP-AF - Treatment Success

Tre

atm

ent s

ucce

ss

(%)

Days

P<0.001)

vs 7.3% (SE 2.9%)

CRYO 69.9% 114/163

Blanked DRUG Rx 7.3% 6/82

30 days

KM estimate 68.6% (SE 3.9%)

11


9/25/2014 3:38 PM

Summary of All Adverse Events (Intention-to-Treat)

Type of Adverse Event CRYO(n = 163)

DRUG(n = 82)

Stroke 4 2.5% 1 1.2%

TIA 3 1.8% 1 1.2%

Tamponade 1 0.6% 1 1.2%

Myocardial infarction 2 1.2% 0 0.0%Hemorrhage requiring transfusion 3 1.8% 1 1.2%

New atrial flutter 6 3.7% 13 15.9%Atrial esophageal fistula 0 0.0% 0 0.0%

Death 1 0.6% 0 0.0%

New or worsened AV fistula 2 1.2% 0 0.0%Pseudoaneurysm 1 0.6% 1 1.2%

Phrenic nerve palsy 22 13.5% 6 7.3%

Persistent phrenic nerve palsy 4 2.5% 0 0.0%PV stenosis 5 3.1% 2 2.4%

Author Study typePts

total (n)Ablation strategy

FU (months, mean + SD)

Arrhythmia free survival (%)

Comp-lications (%)

Gaita2008

randomised 1:1

PVI vs. PVI + LL 204 PVI / PVI+LL41.4±6.2 / 39.7±5.5 41 2%

Fiala2008

randomised 1:1

seg. PVI vs. circumfer. PVI

110 PVI 48±8 56 1%

Bertaglia2009

observational 177 PVI / PVI+LL 49.7±13.3 58 n.r.

Bhargava2009

observational 1404 PVI / PVI+LL 59±16 73 3%

Tsou2010*

observational 123 PVI 71±18 71 n.r.

Wokhlu2010

observational 774 PVI / PVI+LL 36±22.8 64 n.r.

Ouyang2010

observational 161 PVI 57.6 47 2%

Weerasooriya2011

observational 100 PVI / PVI+LL 60 32 6%

Longterm Outcome after PVI

PVI: Pulmonary vein isolation; LL: left lines; n.r.: not reported; seg.: segmental; circumfer.: circumferential *only patients free from AF one year after ablation were included! Regarding to a total of 239 patients who underwent AF ablation: success rate after 71±18 months was only 36.4%!

12


9/25/2014 3:38 PM

In-hospital Complications Associated with Catheter Ablation of AF in USA

Complication Overall

2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 P value

Any procedural complications

6.29 5.33 5.53 6.01 7.17 6.32 5.10 6.17 6.66 5.93 6.49 7.48 0.108

In hospital death

0.42 0.44 0.55 0.63 0.30 0.61 0.15 0.45 0.53 0.27 0.52 0.47 0.492

Neurological (PostopStroke/TIA)

1.02 0.89 1.11 1.79 1.57 1.13 0.68 1.39 0.53 0.78 0.93 1.20 0.013

Postop-hemorrhage

3.38 1.78 2.54 2.53 2.39 3.38 2.77 3.13 3.52 3.75 3.46 4.90 <0.001

Postop-hemorrhage requiring transfusion

0.58 0.30 0.22 0.32 0.30 0.61 0.34 0.45 0.87 0.65 0.44 1.03 0.020

Deshmukh A, et al. Circulation. published online Se ptember 23, 2013;

93,801 AF ablations from 2000 to 2010 . Overall frequency of complications 6.29% with combined cardiac complications (2.54%) and neurological complications (1.02%).

In-hospital mortality was 0.46%. Annual operator (<25 procedures) and hospital volume (<50 procedures) were significantly associat ed with adverse outcomes .

Atrial Fibrillation Ablation Pilot StudyEURObservational Research Programme

1300 pts 12 months FU

4 deaths19 unknown status

90 lost to FU

333 patients with at least 1 recurrence

(26.1%)

944 patients with no recurrence

(73.7%)

AADS: 43.4%No AADs: 56.6%

Adverse Events

In Hosp

12 months

CV 3.3% 2.02%

Brady+PM 0.2% 1.02%

P Vascular 1.3% 0.71%

AV fistula 0.43% 0.47%

Misc

PVsten - 0.08%

PNI 0.14% 0.16%

Eso Ulcer 0.07% -

Death 0.07% 0.31%

Overall 7.7% 2.6%

Brugada J, et al. ESC 2012

13


9/25/2014 3:38 PM

294 Patients Randomized

146 Assigned to RFA

140 Underwent RFA (96%)

After 24 months

N=140; 223 RFA procedures (1.6±0.7)

On AAD: N=13/138 (9%) (IC: 10, III: 3)

Withdrawn N=5

Died N=3

665 7D Holter

recordings69 underwent

repeated RFA

148 Assigned to AAD

146 Started AAD (99%)

After 24 months

N=54; 87 RFA procedures (1.6±0.7)

On AAD: N=100 /137 (73%) (IC: 86, III:14)

Withdrawn N=7

Died N=4

666 7D Holter

recordingsTreatment with

1.24±0.48 AAD’s

MANTRA-PAFFirst Treatment for PAF

Nielsen JC et al AHA 2010

MANTRA-PAF

No significant difference between ablation and drug -therapy groups in the cumulative burden of AF (90th percentile of arrhyth mia burden, 13% and 19%, respectively; P = 0.10) or the burden at 3, 6, 12, or 18 months

Primary end point : cumulative burden of AF (i.e., percentage of time in AF on Holter-monitor recordings)

Nielsen JC et al. NEJM 2012;367:1587-95

● 294 pts randomized; 1.6 RFAs/pt● 194 pts followed for 24 months;

7D Holter

14


9/25/2014 3:38 PM

MANTRA-PAFFirst Treatment for PAF - Results after 24 Months

Nu

mb

er

of

pa

tie

nts

P=0.012

P=0.004140

120

100

80

60

40

20

0

RFA AAD

SAEs RFA AAD

Death 3 4

Stroke 1 0

TIA 1 1

PV stenosis 1 0

Tamponade 3 0

Pericardial

effusion0 1

?perforation 1 0

Atrial flutter, 1:1 0 2

Afl/AT 3 3

CHF 0 2

Total 25 22

No AFSymptomatic Any AFNielsen JC et al AHA 2010

294 pts randomized; 1.6 RFAs/pt194 pts followed for 24 months; 7D Holter

RAAFT-2Radiofrequency Ablation versus AADs for

paroxysmal AF first-line Therapy

• 127 treatment-naïvepatients

• Follow-up for up to 24 months

• Recurrence of AF was less frequent in patients treated with radiofrequency ablation compared with AADs

Morillo CA, et al. JAMA 2014;311(7):692–700

Time to first recurrence of symptomatic atrial tach yarrhythmias

15


9/25/2014 3:38 PM

Recommendations for left atrial ablation

Recommendations Class Level

Catheter ablation of symptomatic paroxysmal AF is recommended in patients who have symptomatic recurrencesof AF on antiarrhythmic drug therapy (amiodarone, dronedarone,

flecainide, propafenone, sotalol) and who prefer further rhythm control therapy, when performed by an electrophysiologist who has received appropriate training and is performing the procedure in an experienced centre.

I A

Catheter ablation of AF should be considered as first-linetherapy in selected patients with symptomatic, paroxysmalAF as an alternative to antiarrhythmic drug therapy,considering patient choice, benefit, and risk.

IIa B

Left Atrial Ablation


Left Atrial Ablation (and AAD)

No or minimal structural heart disease

Paroxysmal Persistent

amiodarone

dronedarone,

flecainide,

propafenone,

sotalol

Catheter ablation

Patient choice

‡

*

Patient choice

Relevant structural heart disease

HF

dronedarone**

/ sotalol ‡ ‡amiodarone

Catheter abla-on ‡

NoYes

Due to AFYes

No

Patient choice* usually pulmonary vein isolation is appropriate

‡ = more extensive left atrial ablation may be needed

** = caution with coronary heart disease ‡ ‡ = contraindicated with LVH


16


9/25/2014 3:38 PM

Consensus Indications for Catheter Ablation for Atrial Fibrillation

RecommendationsSymptomatic AF refractory or intolerant to at least one Class 1 or 3 antiarrhythmic medication

Class Level

Paroxysmal: Catheter ablation is recommended*

I A

Persistent: Catheter ablation is reasonable IIa BLongstanding Persistent:

Catheter ablation may be considered

IIb B

Symptomatic AF prior to initiation of antiarrhythmic drug therapy with a Class 1 or 3 antiarrhythmic agent

Class LevelParoxysmal: Catheter ablation is reasonable IIa B

Persistent: Catheter ablation may be considered

IIb C

Longstanding Persistent:

Catheter ablation may be considered

IIB C

HRS/EHRA/ECAS Consensus Document 2012 Europace, He art Rhythm and JICE

Calkins H,… Camm AJ…

2014 AHA/ACC/HRSGuideline for the Management of Patients With AF

5.6. AF Catheter Ablation to Maintain Sinus Rhythm: Recommendations

Class IAF catheter ablation is useful for symptomatic paro xysmal AF refractory or intolerant to at least 1 class I or III antiarrhyth mic medication when a rhythm control strategy is desired (155-161). (Level of Evidence: A)

Class IIaIn patients with recurrent symptomatic paroxysmal AF , catheter ablation is a reasonable initial rhythm control strategy prior to therapeuti c trials of antiarrhythmic drug therapy , after weighing risks and outcomes of drug and ablation therapy. (Level of Evidence: B)

Class III: HarmAF catheter ablation should not be performed in pat ients who cannot be treated with anticoagulant therapy during and following the procedure. (Level of Evidence: C)

AF catheter ablation to restore sinus rhythm should not be performed with the sole intent of obviating the need for anticoagulation . (Level of Evidence: C)

17


9/25/2014 3:38 PM

On-going AF Ablation TrialsMajor CV Outcomes

Acronym Study Title PI N Endpoint

CASTLE-AF

Catheter Ablation versus Standard conventional Treatment in patients with LEft ventricular dysfunction and Atrial Fibrillation

Brachmann 400All-cause death + heart failure hospitalisations

CABANA

Catheter ABlation versus ANtiarrhythmic drug therapy for Atrial fibrillation

Packer 2000

Composite of total mortality, disabling stroke, serious bleeding, or cardiac arrest

EAST Early Atrial fibrillation Stroke Prevention Trial Kirchhof 3000

All cause mortality + cardiovascular hospitalisations

1° ablation• PVI• WACA• CFEGM• GP

Drug Rx• Rate• Rhythm• w/ antico-

agulation

R

2000 patients: ≥≥≥≥65 yr of age<65 yr w/ ≥≥≥≥1 CVA risk factor2000 patients: ≥≥≥≥65 yr of age<65 yr w/ ≥≥≥≥1 CVA risk factor

Secondary analyses1) NSR vs AF2) ± underlying

heart disease3) AF type

(parox, pers, perm)4) D/C anticoagulation

Recent onset AFEligible for ablation

and drug Rx

Recent onset AFEligible for ablation

and drug Rx

Catheter Ablation vs Antiarrhythmic Drug Therapy for Atrial Fibrillation

CABANA Trial Design

10 Endpoint: total mortality and CV hospitalisations

After Douglas Packer

18


9/25/2014 3:38 PM

Composite primary endpoint:CV death, stroke / TIA,

CHF or ACS hospitalization

Early rhythm controlAntiarrhythmic drug therapy; pulmonary vein isolation (PVI)

In case of AF recurrence:Re-PVI, adaptation of antiarrhythmic

drug therapy

Usual careRate control, supplemented by

rhythm control only in symptomatic patients despite optimal rate control therapy, as mandated by the 2010

ESC guidelines for AF

Study procedures

Outpatient follow-up at months 12, 24, 36 (both study groups)

Antithrombotic therapyTherapy of underlying heart disease (both study groups)

Pre-study screening

RPatients without known AF but

positive on ECG screening

Patients with recent-onset AF

(≤ 1 year)

Patients at risk for cardiovascular events

e.g., recruited in cardiology offices, medicine offices,

emergency departments, cardiology departments, neurology

departments, hypertension clinics,

pacemaker clinics, and others

ECG monitoring of therapy

Early treatment of Atrial fibrillation for Stroke and cardiovascular complications prevention Trial

EAST:

Kirchhof P, et al.

Rhythm Control and Mortality in AFLong term benefit

• Population-based administrative databases, Quebec

• 26,130 patients

• 1999 to 2007

• > 65 years

• AF hospitalization

• No AF-related drug prescriptions < 1year < admission (first documented AF)

• AAD < 7 days > discharge

Ionescu-Ittu R, et al. Arch Intern Med. 2012;172:99 7-1004.

HR

for

rhyt

hm v

s ra

te (

95%

CI)

Years since initiation of AF treatment

0.8

1.0

1.2

1.4

0.6

Lower mortality with rate control

Treatmentinitiation

1 2 3 4 5 6 7 8

Lower mortality with rhythm control

No difference

19


9/25/2014 3:38 PM

AF: Rhythm vs. Rate (drug scripts)Risk of Stroke/TIA

Unadjusted Adjusted

HR 95% CI HR 95% CI

All patients0.72 0.67, 0.78 0.80 0.74, 0.87

CHADS2 = 0n = 4,876

0.86 0.65, 1.13 0.93 0.70, 1.24

CHADS2 = 1N = 15,551

0.71 0.61, 0.83 0.80 0.68, 0.93

CHADS2 ≥ 2N= 37,091

0.77 0.70, 0.84 0.84 0.77, 0.93

Propensity matched

0.75 0.67, 0.85 0.77 0.68, 0.87

Adjusted for sex, co-morbidities, type of AF, treating physician, age, antithrombotic treatments0.5 1.0 1.5 0.5 1.0 1.5

●

●

●

●

●

●

●

●

●

●

Tsadok MA et al Circulation 2012 epub

Population-based observational study of Quebec pts ≥ 65 ys with a diagnosis of AF during the period 1999 – 2007. 16,325 rhythm control, 41,193 rate control. 16,325 matched pairs of pts.

rhythm rate

AF Ablation - Long-term Stroke Rates

Bunch JT, et al. Heart Rhythm 2013;10:1272-77

● 4212 consecutive patients - AF ablation● 16,848 age-/sex-matched controls with AF (no ablation)● 16,848 age-/sex-matched controls without AF

CHADS2 Categories: 0-1, 2-3, `≥ 4

0.5 1.0 1.5 2.0 2.5Hazard Ratio

AF, no ablationvs

no AF

AF, ablationvs

no AF

1.83

1.81

1.83

0.86

0.84

0.87

Increased risk vs. no AF

● Intermountain AF Study● Followed for at least 3 years● Mean age was 65.0 ±13 years

Eve

nt-F

ree

Sur

viva

l

0 2000 4000 6000 8000 10000 12000

Days to CVA

0-1 no AF0-1 AF no ablation0-1 AF ablation2-3 no AF2-3 AF no ablation2-3 AF ablation≥ 4 no AF≥ 4 AF no ablation≥ 4 AF ablation

1.00

0.95

0.90

0.85

0.80

0.75

0.70

20


9/25/2014 3:38 PM

Clinical evaluation

Appropriate antithrombotic therapy

Rhythm control Rate control

Paroxysmal Persistent Permanent

Remains symptomatic

Failure of rhythm control

Choice of Rate and Rhythm Control

Long-standing persistent

Adapted from the ESC AF Guidelines Camm AJ, et al. Europace 2010

Antiarrhythmic Drugs or Ablation?

21


9/25/2014 3:38 PM

Thank you for your attention

What’s the premise for AADs?

• Less invasive approach� highly beneficial for younger patients

� this is often preferential for patients compared to ablation

• Lower risk of complications than for ablation

• AF progression can be halted and sinus rhythm achieved

• The Belgian Health Care Knowledge Centre� Retrospective data from 830 AF ablation patients (2007-2008)

� Ablation has high associated costs (€9600) but may be cost-effective

� Real-world effectiveness of ablation, in Belgium, is disappointing

� Raised serious questions about the evidence that underpins current European guidelines

Van Brabandt H, et al. Europace 2013;15:618–19

22


9/25/2014 3:38 PM

AHA/ACC/HRS Guidelines AADs vs. LA Ablation

• Guidelines recommend AADs as first-line therapy in paroxysmal and persistent AF patients depending on comorbidities such as SHD

Drugs are listed alphabetically. *Catheter ablation is only recommended as first-line therapy for patients with paroxysmal AF, and depends on patient preference when performed in experienced centres §Not recommended with severe LVH ||Should be used with caution in patients at risk for torsades de pointes ventricular tachycardia ¶Should be combined with AV nodal blocking agents. CAD, coronary heart disease; HF, heart failure; LVH, left ventricular hypertrophy

January CT, et al. Circulation 2014;129

**

New data and experience - RCTs

• RAAFT-2 (radiofrequency ablation versus AADs for paroxysmal AF first-line therapy)1

� 127 treatment-naïve patients

� Follow-up for up to 24 months

� Recurrence of AF was less frequent in patients treated with radiofrequency ablation compared with AADs

• SARA (Catheter ablation vs. AADs in treatment of persistent AF)2

� 146 patients� Catheter ablation is superior to

medical therapy for the maintenance of sinus rhythm in patients with persistent AF at 12-month follow-up

1Morillo CA, et al. JAMA 2014;311(7):692–700; 2Mont L, et al. Eur Heart J 2014;35(8):501–7.

Time to first recurrence of symptomatic atrial tachyarrhythmias (RAAFT-2)

Survival curves for patients free of sustained AF episodes at 12 months (SARA)

Cum

ulat

ive

haza

rd r

ate

Follow-up since randomisation, d

Antiarrhythmic drug

Radiofrequency catheter ablation

Sur

viva

l pro

babi

lity

free

of

prim

ary

endp

oint

Follow-up (months after blanking period)

surrey cardiology conference 2014 - st peter's hospital · surrey cardiology conference 2014...

Documents