Global Variations in the 1-year Rates of Death and Stroke in Patients Presenting to the Emergency

Department with Atrial Fibrillation

Results from the RE-LY AF Registry

Background

AF is a major global disease; however, our understanding of AF is based largely on European and N. American studies

Baseline results from the RE-LY AF registry (ESC 2011) demonstrated important regional variations in risk factors and treatment of AF

The RE-LY AF registry followed patients for 1 year to document:

Cause-specific mortality

Clinical outcomes including stroke, embolism, heart failure, major bleeding and hospitalization

47 countries; 164 sites; 15,408 patients

Region Sites Patients Middle East 8 896 North America 18 1817 Africa 21 1137 Latin America 23 1134 India 22 2536 Western Europe 19 1982 China 20 2023 Eastern Europe 22 2542 SE Asia 11 1341

= Participating country

Study Methods

Prospective registry

Atrial fibrillation or atrial flutterPrimary or secondary diagnosis

Presenting to an emergency department

Enrolled between January 2008 and April 2011

Follow-up completed May 2012Occurred 1 year ± 4 weeks after enrolment

Complete FU in 99.4%

Complete reporting of ALL data in 97.7%

Patient Characteristics

Arrhythmia Atrial fibrillation: 98%; Atrial flutter: 2%

Reason for ER visitAF primary diagnosis: 44%; Secondary: 56%

History of AFFirst episode: 21%; Prior history: 79%

Pattern of AFParoxysmal AF: 34%

Persistent AF: 26%

Permanent AF: 40%

Age

N. Am S. Am W. Eur E. Eur Middle E.

Africa India China SE Asia45

50

55

60

65

70

75

80

85

Median; IQR (years)

N. Am S. Am W. Eur E. Eur Middle E.

Africa India China SE Asia

0.0

0.5

1.0

1.5

2.0

2.5

Mean CHADS2 Score

Mortality at 1-year in regional cohorts

N. Am S. Am W. Eur E. Europe

Middle E.

Africa India China SE Asia

0%

5%

10%

15%

20%

25%

- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Crude Mortality

Adjusted Mortality: (for age, sex, heart failure, coronary artery disease, hypertension, diabetes, rheumatic heart disease and reason for emergency department presentation

Global Ave.

Mortality: by Reason for ED Visit

N. Am S. Am W. Eur E. Europe

Middle E.

Africa India China SE Asia

0%

5%

10%

15%

20%

25%

30%

- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Other Primary Diagnosis

Primary Diagnosis of AF

Global Ave.

Heart Failure

Infection Stroke Resp. Failure

Cancer Sudden Death

MI0%

5%

10%

15%

20%

25%

30%

35%

40%

Cause of Death: Global

Proportion of all Deaths

Proportion of Causes of Death by Region

N. Am L. Am W. Eur E. Eur M. East

Africa India China SE Asia

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

StrokeHeart Failure

Stroke rates in the regional cohorts

N. Am S. Am W. Eur E. Europe

Middle E.

Africa India China SE Asia

0%

1%

2%

3%

4%

5%

6%

7%

8%

9%

- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Crude Stroke Rate

Adjusted Stroke Rate: (for age, stroke/TIA, heart failure, hypertension and diabetes). NOT ADJUSTED FOR VKA USE

Global Ave.(Crude)

Stroke rates in the regional cohorts

N. Am S. Am W. Eur E. Europe

Middle E.

Africa India China SE Asia

0%

1%

2%

3%

4%

5%

6%

7%

8%

9%

- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Crude Stroke Rate

Adjusted Stroke Rate: (for age, stroke/TIA, heart failure, hypertension, diabetes and VITAMIN K ANTAGONIST USE)

Global Ave.(Crude)

Stroke Risk: Overall Global by RHD

Crude *Adjusted0.0%0.5%1.0%1.5%2.0%2.5%3.0%3.5%4.0%4.5%

No History of Rheumatic Heart Disease History of Rheumatic Heart Disease

No Rheumatic Heart DiseaseN=13,507

Rheumatic Heart DiseaseN=1788

Age 66.2 years 49.5 years

Female sex 45.4% 64.9%

Coronary Disease

34.3% 5.5%

Hypertension 60.3% 19.6%

Heart Failure 33.0% 34.7%

Warfarin Use 32.0% 68.7%

*Adjusted for age, history of stroke/TIA, heart failure, diabetes, hypertension, region and VKA use

N=1788 patients with RHD

Global CHADS2-Specific Stroke Rate (1-yr.)

0 1 2 3 > 30%2%4%6%8%

10%12%14%

Proportion of Patients with Stroke at 1 year, without RHD

CHADS2: Congestive Heart Failure, Hypertension, Age ≥ 75, Diabetes Mellitus, Prior Stroke or TIA (2)

Proportion of Patients with Stroke at 1 year, with RHD, but no valve surgery

Conclusions

In a global setting more than 10% of patients presenting to an emergency department with AF are dead within 1 year

The rate appears highly variable between different countriesHowever; may be unmeasured bias in types of patients recruited

Mortality is 2-3 times higher when AF is a secondary diagnosis

Despite the availability of modern medical therapy, more than 4% of AF patients experience stroke within one year

Globally, CHADS2 score has a greater influence on stroke risk than the presence of rheumatic heart disease

Most of the difference in stroke rate between regions can be explained on the basis of VKA use

Conclusions II

In a global setting the RELY AF registry

shows very large unmet medical needs

and large opportunities for improvement

by applying currently generally available

modalities for diagnosis, risk stratification

and treatment of patients presenting with

atrial fibrillation

Acknowledgements

Steering committeeJ. Healey*, S. Connolly, S. Yusuf (Canada); J. Oldgren*, L. Wallentin (Sweden); M. Ezekowitz, A. Parekh (USA); A. Avezum (Brazil); P. Jansky (Czech Republic); P. Commerford (South Africa); J. Zhu, Lisheng Liu (China); P. Pais, A. Sigamani (India); A. Damasceno (Mozambique). * co-chairs

Study CoordinationA. Grinvalds, E. Themeles (Canada)

Population Health Research Institute (Canada); Dante Pazzanese Institute Research Division(Brazil); St. John’s Research Institute (India); Fuwai Hospital (China)

Study SponsorBoehringer-Ingelheim: P. Reilly, J. Varrone