Differences in Clinical Outcomes with Rhythm and Rate Control Therapies for Atrial Fibrillation in the RecordAF Registry

A. John Camm

REgistry on Cardiac rhythm disORDers:an international, observational, prospective survey assessing the control ofAtrial Fibrillation

Scientific Committee

Prof. Günter BREITHARDT (Münster, GERMANY)

Prof. John CAMM (London, UK) Prof. Harry CRIJNS (Maastricht, The

NETHERLANDS) Prof. Paul DORIAN (Toronto, CANADA) Prof. Peter KOWEY (Wynnewood, PA , USA)

Prof. Jean-Yves LE HEUZEY (Paris, FRANCE)

Prof. Eric PRYSTOWSKY (Indianapolis, IN, USA) Prof. Peter SCHWARTZ (Pavia, ITALY) Prof. Christian TORP-PEDERSEN (Kobenhavn, DENMARK)

Prof. William WEINTRAUB (Newark, DE, USA)

Presenter Disclosure Information

A. John Camm– Differences in Clinical Outcomes with Rhythm and Rate

Control Therapies for Atrial Fibrillation in the RecordAF Registry

FINANCIAL DISCLOSURE:– Consultant/Advisor and Member of the Speakers’ Bureau

for sanofi aventis– This study was sponsored by sanofi aventis

UNLABELED/UNAPPROVED USES DISCLOSURE:– None

Background

The results of AFFIRM, and other rate versus rhythm trials suggest that there is no advantage of rhythm control over rate control for the treatment of atrial fibrillation with respect to major cardiovascular outcomes

However, randomized controlled trials often do not fully represent real life situations

Registry data may be of value to complement information derived from randomized controlled trials

The RecordAF Registry was established to trace the influence of the physician’s choice of a rate versus rhythm control strategy for consecutive patients with first onset or recent recurrent atrial fibrillation

RecordAF Registry – Enrolment Real-life International, observational, prospective, longitudinal cohort

study from 2007 to 2009 Evaluate management and clinical outcomes in recently diagnosed AF

patients over 1 year

21 countries, 532 randomly chosen general cardiologists sitesn=5604 eligible pts included from May 2007 to April 2008

France

30 Sites

Spain

20 Sites

Portugal

21 Sites

UK

20 Sites

Denmark

10 Sites

Greece

50 Sites

Austria

25 Sites

Poland

20 Sites

Hungary

30 Sites

Russia

50 SitesBelarus

50 Sites

Thailand

10 Sites

Italy

10 Sites

Korea

35 Sites

Philippines

5 Sites

Brazil

10 Sites

Colombia

15 Sites

Mexico

15 Sites

US

100 Sites

Germany

40 Sites

Sweden

22 Sites

RecordAF Registry – Design

Main Inclusion criteria– Age ≥ 18 years – History of atrial fibrillation <1 year– In sinus rhythm or in atrial fibrillation– Eligible for pharmacological treatment of AF

V0Baseline

V16 months

V212 months

Two endpoints at 12 months Rate of therapeutic success of AF management

(SR or at rate control target, + no major CV event + no strategy switch) Rate of major CV events (CV death, myocardial Infarction, stroke, TIA

leading to hospitalization, hospitalization or prolongation of hospitalization (arrhythmic or proarrhythmic events, other CV events, major complications of ablative procedure)

Main Exclusion criteria:– “Permanent” AF– AF due to a transient cause– Post-operative AF

Choice of Strategy at Baseline by Cardiologists

Rhythm control strategy

Rate control strategy

n=5604

0 10 20 30 40 50 60

45.1%

54.9%

n=2528

n=3076

%

Baseline Demographics and AF Status

VariableRhythm control

strategy n=3076

Rate control strategy n=2528

p-value

Age (years), mean (SD) 64 (12.0) 67 (11.6) <0.001

Gender

Male 57% 58% 0.75Body mass index (kg/m2),mean (SD) 28.6 (5.3) 28.3 (5.7) 0.008

Seated systolic blood pressure (mm Hg),mean (SD) 133.5 (18.9) 132.3 (20.0) 0.02

Seated diastolic blood pressure (mm Hg),mean (SD) 79.7 (10.9) 79.5 (11.5) 0.51

Resting heart rate (bpm),mean (SD) 76.6 (20.9) 80.6 (19.1) <0.001

1 year follow-up5171* (92.3%)

Baselinen=5604

RecordAF Registry – Follow-up

* 44 patients (0.8%) had a 6 months F-U only but had a change in strategy or a clinical event by 6 months

No follow up at 1 year

433 (7.7%)

21

18

7

20

41

24

20

9

20

69

17

9

24

3023

7

15

68

8

21

16

43

13

16

0 10 20 30 40 50 60 70 80

Baseline Demographics and Co-morbidities

p<0.001

p<0.001

*p value compares the percentage of the condition between rhythm control vs. rate control

%

n=5604 History Heart Failure

History Dyslipidemia

History Diabetes

Valvular Heart disease

LVEF <40%

History of Myocardial Infarction

Fam. hist. Premature CV Disease

History CAD

History Stroke/TIA

History HTN

Lone AF

HF NYHA I + II

Rhythm control

Rate controlp<0.001

p<0.001

p=0.006

p<0.001

Clinical Presentation of AF at Baselinen=5604

85

39

30

63

6

76

81

63

32

5

0 20 40 60 80 100

Paroxysmal AF

Persistent AF

Symptomatic AF *

Atrial Fibrillation at inclusion

AF first diagnosis

%

* Recorded at the time of baseline visit or during the previous year

Rhythm control

Rate control

Baseline Medication

*p value <0.001 for all comparisons

p<0.001*Rhythm control strategy selected

Rate control strategy selected

n patients

9

45

18

2

2

<1

0 10 20 30 40 50

Class III

Class Ic

Class Ia

%

42

1062

271

178

0 200 400 600 800 1000 1200 1400

Other Class III

drugs

Sotalol

n=5604

51

6

9

72

15

34

0 10 20 30 40 50 60 70 80

Beta-blockers except sotalol

HR lowering calcium-channel

blockers

Cardiac glycosides

%

AF Status at 1 Year

Rhythm StatusRhythm control

n=2879%

Rate controln=2292

%Sinus rhythm at the visit 81 33

Paroxysmal AF 70 30

Persistent AF 17 16

Permanent AF 13 54

Symptoms at the time of the visit 21 20

%

Strategies and Treatment Modifications between Baseline and 1 year

2

12

10

22

55

2

5

9

23

47

5

<1

2

5

1

3

0 10 20 30 40 50 60

Pharmacological conversion

Electrical cardioversion

Change in AF Strategy

Change in Pharmacological AF treatment

Catheter Ablation

Pacemaker Implantation

Surgical AF treatment

New diagnosis other arrhythmias

Rhythm control strategy selected

Rate control strategy selected

n=5171

1st Primary EndpointTherapeutic Success at 1 year

Therapeutic SuccessRhythm controln=2879

%

Rate controln=2292

%p-value

Therapeutic success 60 47 p<0.001Control of AF

81 74

No change in strategy between baseline and 1 year 78 77

No clinical outcome between baseline and 1 year

83 82

Parameters Odds ratio

95% Confidence

Intervalp-value

Strategy (rhythm vs. rate) 1.67 1.45-1.91 <0.0001

CAD 0.79 0.67-0.94 0.0068

Heart failure:

I+II vs. No HF 0.68 0.57-0.80 <0.0001

III+IV vs. No HF  0.64 0.45-0.90 0.0100

Age >75 0.82 0.70-0.96 0.0152

Prior stroke/TIA 0.74 0.58-0.93 0.0115

0.1 1 10

Multivariate Analysis of Baseline Prognostic Factors for Therapeutic Success

Favors therapeutic successDecreases therapeutic success

2nd Primary EndpointClinical Outcomes at 1 year

Clinical EventsRhythm control

n=2879 %

Rate controln=2292

%

Any clinical event 17 18

CV death 1 3

Stroke or TIA 2 3

Myocardial infarction 1 1Hospitalization or prolongation of hospitalization for arrhythmia or pro-arrhythmia 11 7Hospitalization or prolongation of hospitalization for other CV events or interventions: 7 9

Congestive heart failure 2 5

Unstable angina 1 2

Other 4 4Hospitalization or prolongation of hospitalization for major complications of ablative procedure 1 1Hospitalization for CV event

Yes 17 17

p- value = 0.35

Multivariate Analysis of Baseline Prognostic Factors for Clinical Outcomes

Parameters Odds ratio

95% Confidence

Intervalp-value

Heart rate (for 1 bpm increase) 1.009 1.004-1.01 0.0002

CAD 1.69 1.37-2.08 <0.0001

Renal disease 2.11 1.54-2.89 <0.0001Duration of AF ( 3 months vs. <3 months) 0.82 0.69-0.97 0.0239

Symptoms 1.68 1.27-2.24 0.0003

Heart failure:

I+II vs. No HF 1.49 1.20-1.85 0.0003

III+IV vs. No HF  2.03 1.38-2.99 0.0003

Age >75 1.26 1.02-1.55 0.0359

Prior stroke/TIA 1.63 1.22-2.17 0.0009

0.1 1 10Increases clinical outcomesDecreases clinical outcomes

RecordAF Registry - Conclusions

In a cardiology setting rhythm control was preferred (55%) AF progressed more rapidly to a permanent status at

1 year with rate control (54%) than with rhythm control (13%) Therapeutic success was achieved more frequently in patients

treated by rhythm control (60% vs. 47%), driven by 81% in SR in the rhythm control group and 74% at HR target of ≤ 80 bpm at1 year in the rate control group

The high occurrence of CV clinical events was dependent on co-morbidity rather than the choice of strategy

In real life, the better success of AF management with rhythm control did not translate into better outcomes

These results confirm and complement results from previous controlled randomized trials