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

1. Differences in Clinical Outcomes with Rhythm and Rate Control Therapies for Atrial Fibrillation in the RecordAF Registry A. John Camm REgistryonCardiacrhythmdisORDers:an international, observational, prospective survey assessing the control ofAtrialFibrillation

2. 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)

3. 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

4. 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

5. Russia Sweden Belarus 50 Sites 22 Sites 50 Sites US Germany Hungary 100 Sites Portugal UK France Denmark 40 Sites 30 Sites 10 Sites 21 Sites 20 Sites 30 Sites Korea Poland Greece Austria Mexico Colombia Brazil Spain 20 Sites 10 Sites 15 Sites 25 Sites 20 Sites 35 Sites 15 Sites 50 Sites Italy 10 Sites Thailand Philippines 10 Sites 5 Sites 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 sites n=5604 eligible pts included from May 2007 to April 2008

6. 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 • Main Exclusion criteria: • “Permanent” AF • AF due to a transient cause • Post-operativeAF V0 Baseline V1 6 months V2 12 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)

7. Choice of Strategy at Baseline by Cardiologists n=5604 Rate control strategy Rhythm control strategy n=2528 45.1% n=3076 54.9% %

8. Baseline Demographics and AF Status

9. RecordAF Registry – Follow-up Baseline n=5604 1 year follow-up 5171* (92.3%) No follow up at 1 year 433 (7.7%) * 44 patients (0.8%) had a 6 months F-U only but had a change in strategy or a clinical event by 6 months

10. Rate control Rhythm control Baseline Demographics and Co-morbidities n=5604 p<0.001 History Heart Failure p<0.001 HF NYHA I + II LVEF <40% p<0.001 History Stroke/TIA p=0.006 History Diabetes History HTN History CAD History of Myocardial Infarction Fam. hist. Premature CV Disease p<0.001 Valvular Heart disease History Dyslipidemia % p<0.001 Lone AF *p value compares the percentage of the condition between rhythm control vs. rate control

11. Clinical Presentation of AF at Baseline Rate control Rhythm control n=5604 AF first diagnosis Paroxysmal AF Persistent AF Atrial Fibrillation at inclusion Symptomatic AF * % * Recorded at the time of baseline visit or during the previous year

12. Rate control strategy selected Rhythm control strategy selected Baseline Medication n=5604 p<0.001* Other Class III drugs Sotalol % n patients Cardiac glycosides *p value <0.001 for all comparisons HR lowering calcium-channel blockers Beta-blockers except sotalol %

13. AF Status at 1 Year

14. Rate control strategy selected Rhythm control strategy selected Strategies and Treatment Modifications between Baseline and 1 year n=5171 Change in Pharmacological AF treatment Change in AF Strategy Electrical cardioversion Pharmacological conversion Catheter Ablation Pacemaker Implantation Surgical AF treatment New diagnosis other arrhythmias %

15. 1st Primary EndpointTherapeutic Success at 1 year

16. Multivariate Analysis of Baseline Prognostic Factors for Therapeutic Success 0.1 1 10 Decreases therapeutic success Favors therapeutic success

17. 2nd Primary EndpointClinical Outcomes at 1 year p- value = 0.35

18. Multivariate Analysis of Baseline Prognostic Factors for Clinical Outcomes 0.1 1 10 Decreases clinical outcomes Increases clinical outcomes

19. RecordAF Registry - Conclusions • In a cardiology setting rhythm control was preferred (55%) • AF progressed more rapidly to a permanent status at1 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