Hamon M 1, Nienaber C 2, Galli S 3, Huber K 4, Gulba D 5, Hill J 6, Lafont A 7, Cequier A 8, Bernstein D 9, Deliargyris E 9 Institutions: 1. Centre Hospitalier Universitaire de Caen, France. 2. Department of Cardiology and Angiology, University Hospital Rostock, Rostock School of Medicine, Rostock, Germany. 3. Department of Cardiovascular Sciences, University of Milan, Centro Cardiologico Monzino, IRCCS, Milan, Italy. 4. Third Department of Medicine, Cardiology and Emergency Medicine, Wilhelminen hospital, Vienna, Austria. 5. Department of Cardiology, Krankenhaus Düren, Düren, Germany. 6. King's College Hospital, King's College, London, UK. 7. Cardiology Department, University Paris-Descartes; AP-HP; European Georges Pompidou Hospital, Paris, France. 8. Hospital de Bellvitge, Barcelona, Spain. 9. The Medicines Company, Parsippany NJ, USA. In hospital and 30 day outcomes in all-comer PCI with bivalirudin: Initial report of the prospective EUROVISION Registry 1

Purpose and Methods ● Eurovision was a prospective observational study conducted in 58 European sites to track utilization patterns of bivalirudin in PCI. ● Outcomes were collected for ischemic events (death, MI, stroke and urgent revascularization), and bleeding in hospital and at 30 days ● Major bleeding, ACUITY definition (any one of the following): Intracranial, retroperitoneal, or intraocular bleeding, access site hemorrhage requiring radiological or surgical intervention, ≥5 centimeter(cm) diameter hematoma at puncture site, decrease in hemoglobin (Hgb) concentration of ≥4 g/dl without an overt source of bleeding, decrease Hgb concentration of ≥3 g/dl with an overt source of bleeding, re-operation for bleeding, any blood product transfusion ● Minor bleeding was any bleeding not included in the definition of major bleeding 2

Methods ● A total of 2018 consecutive bivalirudin-treated patients were included from 58 sites in 5 countries ● Germany (31.1%) ● France (28.9%) ● Italy (19.0%) ● Austria (17.0%) ● United Kingdom (4.0%) ● In-hospital and 30-day outcomes were collected and included: Death, MI, stroke, revascularization, major and minor bleeding, stent thrombosis and thrombocytopenia 3

Baseline characteristics 4 n/N Bivalirudin (N=2018) Age (yrs), mean ± SD65.5 ± 11.9 Age >65 yr1122 / % Female499 / % Weight (kg) mean ± SD79.8 ± 14.9 Prior MI486 / % Dyslipidemia1215 / % Prior PCI636 / % Hypertension1385 / % Previous CABG145 / % Congestive Heart Failure130 / % Current Smoker588 / % Family history of PVD405 / % Diabetes482 / %

Procedural characteristics 5 n/N Bivalirudin (N=2018) # diseased vessels >11086 / % Actual treatment PCI1933 / % Actual treatment CABG13 / % Medical management70 / % Femoral access1353 / % Radial access580 / % Intervention Type: Balloon Angioplasty883 / % Drug-Eluting Stent1219 / % Non drug-Eluting Stent626 / % Procedure duration, mean ±SD36.0 ± 43.6 GP IIb/IIIa use85 / %

Distribution of study population Overall, 58% of patients were cardiac marker -positive 6 N=523 N=315 N=499 N=678

Results ● Overall, P2Y 12 inhibitor preloading occurred in 95% of patients ● 91% clopidogrel (65% with 600 mg, 33% with 300 mg) ● 9% prasugrel ● 45% of patients received other antithrombin therapy prior to PCI and were then switched to bivalirudin ● Activated clotting time was checked in only 2.8% suggesting operator familiarity with bivalirudin predictable mode of action and treatment effect 7

Outcomes 8 D/ MI/ UrR/ Stroke/ Major bleed Major bleed Stroke Death MI Urgent revasc

Independent predictors of ischemic events and major bleeding Odds Ratio (95% CI) P- value Ischemic events (D/MI/Urgent revasc/Stroke) Congestive heart failure 2.37 [ ]0.011 Major bleeding (ACUITY) Renal impairment3.99 [ ]<0.001

Stent thrombosis by diagnosis ● Overall rate of stent thrombosis 0.3% (6/2018)

Outcomes by post-PCI infusion Bivalirudin post-PCI infusion n=916 Bivalirudin no post-PCI infusion n=1017 Death/ MI/ Stroke/ Revasc2.4%3.3% Death/ MI/ Revasc/ Stroke/ Major Bleed 3.4%5.1% Death0.9%1.2% Stent thrombosis0.4%0.2% Acute0.1% Sub-acute0.3%0.1% Major bleed1.1%2.0% Among STEMI patients, 62% received a post-procedural bivalirudin infusion for a median duration of 122 minutes 11

Conclusion ● Adaptation of bivalirudin as the foundation for all- comer PCI (including high percentage of STEMI and NSTEMI patients) is associated with excellent ischemic protection and safety, ● The rates observed in EUROVISION compare favorably to other large existing registry datasets. 12