1. Results of the 1 st Phase of the International GLORIA-AF Registry Program: Regional Treatment Differences Before the Era of Novel Anticoagulants MV Huisman, CS Ma, HC Diener, SJ Dubner, JL Halperin, KJ Rothman, C Teutsch, A Clemens, K Zint, E Kleine, DB Bartels, GYH Lip for the GLORIA-AF Investigators

2. Background 2 Atrial fibrillation (AF) is the most common cardiac arrhythmia, and confers an increased mortality and morbidity from stroke and thromboembolism. Until recently, Vitamin K antagonists (VKA) were the gold standard treatment for stroke prevention Non-VKA oral anticoagulants (NOACs), like dabigatran, are changing treatment patterns of AF patients Information from registries would increase our understanding of ‘real world’ management of AF and related outcomes GLORIA-AF is a large, international, observational registry program of patients with newly diagnosed AF at risk of stroke

3. Am Heart J 2014;167:329-34.

4. up to 56,000 patients 2,200 sites up to 50 countries GLORIA-AF Registry Program – All Phases GLORIA -AF General practices Specialist offices Community hospitals University hospitals Outpatient care centres Anticoagulation clinics

5. Region 2 Europe Denmark, France, Germany, Ireland, Italy, Greece, Switzerland, Norway, Netherlands, Portugal, Spain, Sweden, UK, Austria, Czech Republic, Croatia, Romania, Bulgaria, Estonia, Latvia, Lithuania, Slovakia, Slovenia) Region 2 Europe Denmark, France, Germany, Ireland, Italy, Greece, Switzerland, Norway, Netherlands, Portugal, Spain, Sweden, UK, Austria, Czech Republic, Croatia, Romania, Bulgaria, Estonia, Latvia, Lithuania, Slovakia, Slovenia) Region 1 Asia China, Korea, Russia, Hong Kong, Singapore, Taiwan, India Region 1 Asia China, Korea, Russia, Hong Kong, Singapore, Taiwan, India Region 3 North America USA, Canada Region 3 North America USA, Canada Region 4 Latin America Argentina, Brazil, Ecuador, Mexico, Peru, Venezuela, Colombia, Chile Region 4 Latin America Argentina, Brazil, Ecuador, Mexico, Peru, Venezuela, Colombia, Chile Region 5 Africa / Middle East Lebanon, UAE, KSA, Egypt, Turkey, South Africa Region 5 Africa / Middle East Lebanon, UAE, KSA, Egypt, Turkey, South Africa To date 11,661 patients enrolled word wide in Phase II of the registry ~ 1000 sites activated GLORIA-AF Worldwide

6. GLORIA-AF Phase I Objectives To characterize the newly diagnosed non-valvular AF patient population at risk for stroke and the selection of antithrombotic treatment for stroke prevention in a real-life setting Before NOACs are approved for the prevention of strokes and systemic emboli in different regions of the world (May 2011 – Jan 2013) 6 Last country to approve NOACs (=dabigatran etexilate as the first) in our dataset was China in January 2013

7. 7 (N=291) (N=59) (N=713) Patient Disposition by Region Total patient numbers = 1063

8. Categorization of AF (All Patients) 8 33,8 % persistent 3,7 % permanent

9. Patient Demographics & Medical history 9 DemographicsAsia N=713 Europe N=291 Middle East N=59 Age (years) Median (IQR)69.0 (59.0-77.0) 71.0 (64.0-79.0)65.0 (57.0-74.0) Female N(%)305 (42.8) 147 (50.5)34 (57.6) BMI Median (IQR)23.9 (21.5-26.1) 28.1 (25.4-31.2)27.3 (24.2-33.3)

10. Patient Demographics & Medical history 10 Medical HistoryAsia N=713 (100%) Europe N=291 (100%) Middle East N=59 (100%) Previous stroke 73 (10.2) 31 (10.7)6 (10.2) Myocardial infarction (MI) 59 (8.3) 32 (11.0)8 (13.6) Coronary artery disease (CAD) 181 (25.4) 59 (20.3)16 (27.1) Congestive heart failure 176 (24.7) 65 (22.3)15 (25.4) History of hypertension 500 (70.1) 248 (85.2)47 (79.7) Diabetes mellitus139 (19.5) 79 (27.1)22 (37.3) Chronic gastrointestinal diseases61 (8.6) 9 (3.1)3 (5.1)

11. Stroke and bleeding risk scores 11 Asia N=713 (100%) Europe N=291 (100%) Middle East N=59 (100%) CHADS 2 score class Low (score=0) Moderate (score=1) High (score ≥2) 84 (11.8) 270 (37.9) 359 (50.4) 16 (5.5) 95 (32.6) 180 (61.9) 2 (3.4) 21 (35.6) 36 (61.0) CHA 2 DS 2 VAS C score class Low (score=0) Moderate (score=1) High (score ≥2) 0 184 (25.8) 529 (74.2) 0 (0.0) 36 (12.4) 255 (87.6) 0 (0.0) 6 (10.2) 53 (89.8) HAS-BLED score class Low (score <3) High (score ≥3) Missing 596 (83.6) 88 (12.3) 29 (4.1) 224 (77.0) 23 (7.9) 44 (15.1) 40 (67.8) 10 (16.9) 9 (15.3)

12. Antithrombotic treatment choice at baseline by region all eligible 12 * 19 patients from Middle East and 1 patient from Europe are/is excluded from this table as they received NOACs 49.6 % 4.1 % 20.3 % 63.9 % 25.4 % Antiplt. 25.4 % None 8.6 % Antiplt. 3.4 % ASA 25.4 %

13. Conclusions Data collection from the time prior to NOACs entering the market (Phase I) included1063 patients with 67% of the patients from China 1 st Phase of GLORIA-AF shows lower VKA use in those with paroxysmal AF, and in those with low stroke risk. Geographical differences exists in the use of VKA therapy in the era before the availability of NOACs - notably lower use of VKA in Asia. In Asia, most patients are treated with antiplatelet agents or do not get any antithrombotic treatment. The shift to more VKA use in patients with AF can be seen when “going West”. 13

14. Acknowledgements Scientific Steering Committee MV Huisman, Leiden University Medical Center, Netherlands (Chair) GYH Lip, University of Birmingham, UK (Co-Chair) HC Diener, Universitätsklinikum Essen, Germany SJ Dubner, Clinica y Maternidad Suizo, Argentina JL Halperin, Mount Sinai School of Medicine, USA CS Ma, Beijing An Zhen Hospital, China KJ Rothman, Harvard School of Public Health, USA 14 Boehringer Ingelheim Study Team DB Bartels A Clemens E Kleine Liz Nacar M Paquette C Teutsch K Zint