Increasing Prevalence of Atrial Fibrillation andFlutter in the United States

The present retrospective study estimated the current and projected prevalence of AF and atrial flutter (AFL) in the United States using a large national database. Of the 21,648,681 patients in the databases, 242,903 (1.12%) had nontransient AF and/or AFL (222,605 AF only, 5,376 AFL only, and 14,922 AF and AFL).

Nacarelli GV et al. Am J Cardiol 2009;104:1534–1539.

Increasing Prevalence of Atrial Fibrillation andFlutter in the United States

The present retrospective study estimated the current and projected prevalence of AF and atrial flutter (AFL) in the United States using a large national database. Of the 21,648,681 patients in the databases, 242,903 (1.12%) had nontransient AF and/or AFL (222,605 AF only, 5,376 AFL only, and 14,922 AF and AFL).

Nacarelli GV et al. Am J Cardiol 2009;104:1534–1539.

Increasing Prevalence of Atrial Fibrillation andFlutter in the United States

Co-morbid conditions in patients with AF and/or AFL and in matched controls

Nacarelli GV et al. Am J Cardiol 2009;104:1534–1539.

Development of a risk score for atrial fibrillation(Framingham Heart Study): a community-based cohort study

We assessed 4764 participants in the Framingham Heart Study from 8044 examinations (55% women,45–95 years of age) undertaken between June, 1968, and September, 1987. Thereafter, participants were monitored for the first event of atrial fibrillation for a maximum of 10 years. Multivariable Cox regression identified clinical risk factors associated with development of atrial fibrillation in 10 years.

Schnabel RB et al. Lancet 2009; 373: 739–745.

Estimated ORs and Corresponding SEs and 95% Cis for Prevalence of AF/AFL during follow-up

Atrial Fibrillation at Baseline and DuringFollow-Up in ALLHAT (Antihypertensive and

Lipid-Lowering Treatment to Prevent Heart Attack Trial)

Haywood LJ et al. JACC 2009; 54: 2023-2031.

Haywood LJ et al. JACC 2009; 54: 2023-2031.

Kaplan-Meier event curves for all-cause mortality, coronary heart disease (CHD), stroke, and heart failure (HF) among chlorthalidone, amiodipine, and lisinopril participants with atrial fibrillation (AF) or atrial flutter (AFL) at trialentry (n 334) compared with those without AF/AFL (n 30,370).

Haywood LJ et al. JACC 2009; 54: 2023-2031.

Kaplan-Meier cumulative event curves for all-cause mortality in chlorthalidone, amiodipine, and lisinopril participants with AF/AFL at trial entry or occurring during follow-up (n 821) compared with mortality in thosewithout AF/AFL (n 27,247).

Risk of atrial fibrillation in dipper and nondipper sustainedhypertensive patients

Goto S et al. Am Heart J 2008;156:855-863.

The occurrence of AF was evaluated in 1141 patients aged >=40 years with sustained hypertension (clinic BP >=140 and/or 90mmHg and daytime BP >=135 and/or 85 mmHg). During the follow-up (6.1 ±3.2, range 0.5–12.9 years), AF occurred in 43 patients. The AF rate per 100patient-years in dippers and nondippers was 0.38 and 1.13, respectively. AF free survival was significantly different between the groups (P = 0.0002).

Prevalence, clinical profile, and cardiovascularoutcomes of atrial fibrillation in patients with atherothrombosis

Goto S et al. Am Heart J 2008;156:855-863.

The REduction of Atherothrombosis for Continued Health (REACH) Registry is a large, contemporary, representative, andgeographically diverse cohort of stable outpatients with or at high risk of atherothrombosis. A total of 68,236 patients witheither established atherothrombotic disease (coronary artery disease [CAD], peripheral artery disease [PAD], cerebrovascular disease [CVD]) or at least 3 risk factors [RFO] for athrothrombosis were enrolled.

FA prevalence 6,2 % 12,5 % 13.7 % 11,5 %

Prevalence, clinical profile, and cardiovascularoutcomes of atrial fibrillation in patients with atherothrombosis

Event rates for CV death/MI and stroke of patients with versus without history of AF (adjusted for age, sex, smoking, diabetes, hypertension, hypercholesterolemia).

Goto S et al. Am Heart J 2008;156:855-863.

Relation of Kidney Function and Albuminuria With AtrialFibrillation (from the Heart and Soul Study)

Vagaonescu TD et al. Hypertension. 2008;51:1552-1556.

The Heart and Soul Study is a prospective cohort study designed to examine the impact of psychosocial factors on CAD progression.

Relation of Kidney Function and Albuminuria With Atrial

Fibrillation (from the Heart and Soul Study)

Vagaonescu TD et al. Hypertension. 2008;51:1552-1556.

Dabigatran versus Warfarin in Patients with Atrial Fibrillation

Stuart J. Connolly, M.D., Michael D. Ezekowitz, M.B., Ch.B., D.Phil., SalimYusuf, F.R.C.P.C., D.Phil., John Eikelboom, M.D., Jonas Oldgren, M.D., Ph.D., Amit Parekh, M.D., Janice Pogue, M.Sc., Paul A. Reilly, Ph.D.,

Ellison Themeles, B.A., Jeanne Varrone, M.D., Susan Wang, Ph.D., Marco Alings, M.D., Ph.D., Denis Xavier, M.D., Jun Zhu, M.D., Rafael Diaz, M.D., Basil S. Lewis, M.D., Harald Darius, M.D., Hans-Christoph Diener, M.D.,

Ph.D., Campbell D. Joyner, M.D., Lars Wallentin, M.D., Ph.D., and the RE-LY Steering Committee and Investigators*

The New England Journal of MedicineSeptember 17, 2009 vol. 361 no. 12

16

RE-LY TRIAL UNITED STATES SITES

17

RE-LY TrialParticipating Countries Worldwide

18

RE-LYDabigatran for Stroke Prevention in Atrial Fibrillation

Non-valvular atrial fibrillation at moderateto high risk of stroke or systemic embolism

(at least one high risk factor)

Dabigatran Etexilate150 mg b.i.d. PO

N=6000

Warfarin1 mg, 3 mg, 5 mg PO

(INR 2.0-3.0)N=6000

Dabigatran Etexilate110 mg b.i.d. PO

N=6000

• Primary objective: Noninferiority to warfarin

• Minimum 1 year of follow-up, maximum of 3 years and mean of 2 years of follow-up

• Primary end point: Stroke + systemic embolism

Ezekowitz MD …Wallentin l et al. Am Heart J. 2009;157:805-810.

19

Dabigatran 110vs. warfarin

AC experience

AC naïve

Dabigatran 150vs. warfarin

AC experienceAC naïve

Non-inferiority P

< 0.001

< 0.001

0.003

< 0.001

< 0.001

< 0.001

SuperiorityP

0.34

< 0.001

0.50 0.75 1.00 1.25 1.50M

argi

n =

1.46

HR (95% CI)

RE–LY: 1° EndpointDabigatrannoninferior

Dabigatransuperior

Ezekowitz MD. ESC 2009; Connolly SJ, Ezekowitz MD, et al. N Engl J Med. 2009;361:1139-1151.

21

Atrial Fibrillation Phase 3 Study Estimated Timelines

2009 2010 2011 2012

ROCKETEstimated completion June 2010

Rivaroxaban

RELYComplete

Dabigatran

AVERROES Estimated completion April 2010

ARISTOTLEEstimated completion

November 2010

BOREALISEstimated completion

2011

ENGAGE-AFEstimated completion

2011

Idraparinux Edoxaban

November 2009

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