APPRAISE-2: Phase III Acute Coronary Syndrome

• Sponsor: Bristol-Myers Squibb (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00831441
• Collaborator: Pfizer (Industry), Duke Clinical Research Institute (Other)
• Enrollment: 7,484
• Locations: 1014
• Arms: 2
• Duration (Months): 24
• Patients Per Site: 7.4
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose of this study is to determine if apixaban is superior to placebo for preventing cardiovascular death, non-fatal myocardial infarction, or ischemic stroke in subjects with a recent acute coronary syndrome

Condition or Disease	Intervention/Treatment	Phase
Acute Coronary Syndrome	Drug: Apixaban; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 7484 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Prevention
• Official Title: Apixaban for Prevention of Acute Ischemic Events - 2 A Phase 3, Randomized, Double-Blind, Evaluation of the Safety and Efficacy of Apixaban In Subjects With a Recent Acute Coronary Syndrome
• Study Start Date: Mar 1, 2009
• Actual Primary Completion Date: Mar 1, 2011
• Actual Study Completion Date: Mar 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Apixaban	Drug: Apixaban; Tablets, Oral, 5 mg, twice daily, until study end; Other Names: BSM-562247
Placebo Comparator: Placebo	Drug: Placebo; Tablets, Oral, 0 mg, twice daily, until study end

Outcome Measures

Primary Outcome Measures

1. Event Rate of Cardiovascular Death, Myocardial Infarction, or Ischemic Stroke During the Intended Treatment Period - Randomized Participants [Randomization (Day 1) to first event (CV death, MI, ischemic stroke), up to March 2011, approximately 2 years]

   Event rate was percent of participants with an event of cardiovascular (CV) death, myocardial infarction (MI), or ischemic stroke (number of participants with event/number randomized) per 100 patient (100-pt) years. Study was terminated early and last patient, last visit was in Year 2. Only events confirmed by the adjudication committee were included in the analyses. CV death included deaths due to CV causes (eg, cardiogenic shock, heart failure, arrhythmia/sudden death, cardiac rupture, ischemic stroke, pulmonary embolism, venous/arterial thrombotic events) and other sudden deaths for which an alternative cause was not identified. Intended Treatment Period: the period that started on the day of randomization and ended at the efficacy cut-off date (cut-off date: the date all sites were informed that study drug should be discontinued for all participants, 18 November 2010).

2. Event Rate of Confirmed Major Bleeding Using Thrombolysis in Myocardial Infarction (TIMI) Criteria During the Treatment Period - Treated Participants [From first dose to first occurrence of event (TIMI major bleeding) during Treatment Period (first dose to last dose + 2 days), up to March 2011, approximately 2 years]

   TIMI Major Bleed Criteria: Fatal bleeding, intracranial hemorrhage, and clinically overt bleeding with a hemoglobin (Hgb) drop of ≥ 5 grams per deciliter (g/dL), or ≥15% absolute decrease in hematocrit. To account for transfusions, Hgb measurements were adjusted for transfusions. A transfusion of 1 unit of blood was assumed to result in an increase by 1 g/dL in Hgb or 3% in hematocrit. Event rate was percent of participants with an event of Major Bleed as per TIMI (number of participants with event/number randomized) per 100 patient (100-pt) years. Only events confirmed by the adjudication committee were included in the analyses. Treatment Period=events with onset from first dose to last dose plus 2 days.

Secondary Outcome Measures

1. Event Rate of Unstable Angina (UA) During the Intended Treatment Period - Randomized Participants [Randomization (Day 1) to first event of UA, up to March 2011, approximately 2 years]

   Unstable Angina (UA) defined as worsening or recurrent severe or repetitive angina symptoms at rest lasting at least 10 minutes with at least 2 of the following: New and dynamic electrocardiogram (ECG) changes; angina symptoms leading to inpatient hospitalization; angina symptoms leading to an unplanned or urgent cardiac catheterization, with or without revascularization, that showed evidence of hemodynamically and clinically significant stenosis. Event rate was percent of participants with an event of unstable angina (number of participants with event/number randomized) per 100 patient (100-pt) years. Only events confirmed by the adjudication committee were included in the analyses. Intended Treatment Period: the period that started on the day of randomization and ended at the efficacy cut-off date (cut-off date: the date all sites were informed that study drug should be discontinued for all participants, 18 November 2010).

2. Event Rate of Stroke During the Intended Treatment Period - Randomized Participants [Randomization (Day 1) to first event (stroke), up to March 2011, approximately 2 years]

   Event rate was percent of participants with an event of stroke (number of participants with event/number randomized) per 100 patient (100-pt) years. Only events confirmed by the adjudication committee were included in the analyses. Diagnosis of stroke required a new, non-traumatic, focal neurological deficit of sudden onset, lasting at least 24 hours that was not due to a readily identifiable non-vascular cause (ie, brain tumor). All strokes were classified as hemorrhagic (documentation on imaging (eg computed tomography scan or magnetic resonance imaging) of hemorrhage in the cerebral parenchyma, or a subdural or subarachnoid hemorrhage), non-hemorrhagic/ischemic stroke, ischemic stroke with hemorrhagic conversion, or type unknown. Intended Treatment Period: the period that started on the day of randomization (Day 1) and ended at the efficacy cut-off date (notification of study termination).

3. Event Rate of Myocardial Infarction (MI) During the Intended Treatment Period - Randomized Participants [Randomization (Day 1) to first event (MI), up to March 2011, approximately 2 years]

   MI took into account whether the participant had a recent percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery. Selected key criteria: Elevation of cardiac biomarkers (eg, Creatine Kinase MB fraction (CKMB), Troponin T, Troponin I) above the upper reference limit (URL) plus ischemic symptoms, ECG changes, or imaging evidence of new loss of viable myocardium or new regional wall motion abnormality; Death of CV etiology with new ST-segment elevation or left bundle branch block (LBBB) or fresh intracoronary thrombus by angiography or at autopsy occurring before biomarkers could be obtained or before their appearance in the blood; Following a PCI, elevation of cardiac biomarkers more than 3*URL; Following CABG surgery, elevation of cardiac biomarkers more than 5*URL; New, significant (≥0.04 s) Q waves in ≥2 contiguous leads; Pathologic findings of acute MI. Intended Treatment Period: Day of randomization (Day 1) to efficacy cut-off notice.

4. Event Rate of Stent Thrombosis During the Intended Treatment Period - Randomized Participants [Randomization (Day 1) to first event (stent thrombosis), up to March 2011, approximately 2 years]

   Stent thrombosis: Definite stent thrombosis considered to have occurred by either angiographic or pathological confirmation; Probable stent thrombosis considered to have occurred in the following cases: any unexplained death within the first 30 days after stent implantation; irrespective of the time after the procedure, any MI that was related to documented acute ischemia in the territory of the implanted stent without angiographic confirmation of stent thrombosis and in the absence of any other obvious cause; Possible stent thrombosis considered to have occurred with any unexplained death from 30 days after intracoronary stenting until end of study (in Year 2). Event rate was percent of participants with an event of stent thrombosis (number with event/number randomized) per 100-pt years. Only events confirmed by the adjudication committee were included in the analyses. Intended Treatment Period: Day of randomization (Day 1) to efficacy cut-off notice of study termination.

5. Event Rate of Composite of Cardiovascular Death, Myocardial Infarction, Unstable Angina, or Ischemic Stroke During the Intended Treatment Period - Randomized Participants [Randomization (Day 1) to first event (CV death, MI, UA, Ischemic Stroke, up to March 2011, approximately 2 years]

   Event rate was percent of participants with an event of CV death, MI, unstable angina (UA), or ischemic stroke (number of participants with event/number randomized) per 100-pt years. Only events confirmed by the adjudication committee were included in the analyses. Each type of event was counted once per participant, but participants could have been counted in multiple categories. Intended Treatment Period: Day of randomization (Day 1) to efficacy cut-off date (notification of study termination).

6. Event Rate of Composite of Cardiovascular Death, Fatal Bleed, Myocardial Infarction, or Stroke During the Intended Treatment Period - Randomized Participants [Randomization (Day 1) to first event (CV death, Fatal Bleed, MI, or stroke), up to March 2011, approximately 2 years]

   Event rate was percent of participants with an event of CV death, fatal bleed, MI, or stroke (number of participants with event/number randomized) per 100 patient (100-pt) years. Only events confirmed by the adjudication committee were included in the analyses. CV death included deaths due to CV causes; Diagnosis of stroke required a new, non-traumatic, focal neurological deficit of sudden onset, lasting at least 24 hours that was not due to a readily identifiable non-vascular cause; Fatal bleeding defined as bleeding that Adjudication Committee determined was the primary cause of death or contributed directly to death; MI took into account whether the participant had a recent PCI or CABG surgery. Intended Treatment Period: Day of randomization (Day 1) to efficacy cut-off date (notification of study termination).

7. Event Rate of Composite of All-Cause Death, Myocardial Infarction, or Stroke During the Intended Treatment Period - Randomized Participants [Randomization (Day 1) to first event (All Cause Death, MI, or Stroke), up to March 2011, approximately 2 years]

   Cause of death was determined by the principal condition that caused the death, not the immediate mode of death. CV death: included deaths due to CV causes. Non-CV death: included non-CV deaths caused primarily by a malignancy, infection, bleeding, trauma, non-CV system organ failure, or non-CV surgery. Unknown: included deaths that were not attributable to one of the above categories of CV death or to a non-CV cause. MI accounted whether the participant had a recent PCI or CABG surgery. Diagnosis of stroke required a new, non-traumatic, focal neurological deficit of sudden onset, lasting at least 24 hours that was not due to a readily identifiable non-vascular cause. Only events confirmed by the adjudication committee were included in analyses. Intended Treatment Period: Day of randomization (Day 1) to efficacy cut-off date (notification of study termination).

8. Event Rate of Confirmed Major Bleeding Using International Society on Thrombosis and Hemostasis (ISTH) Criteria During the Treatment Period - Treated Participants [From first dose to first occurrence of event (ISTH major bleed) during Treatment Period (first dose to last dose + 2 days), up to March 2011, approximately 2 years]

   ISTH Criteria: Acute clinically overt bleeding defined as new onset, visible bleeding or signs or symptoms suggestive of bleeding confirmed by imaging techniques, which can detect the presence of blood (eg, ultrasound, CT, MRI). Major bleeding: acute clinically overt bleeding accompanied by one or more of the following: A decrease in Hgb of 2 g/dL or more over 24 hours; A transfusion of 2 or more units of packed red blood cells (RBCs); Bleeding that occurs in at least one of the following sites: intracranial, intraspinal, intraocular (within the corpus of the eye; thus, a conjunctival bleed is not an intraocular bleed), pericardial, intra-articular, intramuscular with compartment syndrome, retroperitoneal; Bleeding that was fatal. Bleeding events were adjudicated by the Adjudication Committee. Event rate was percent of participants with an event (number with event/number randomized) per 100-pt years. Treatment Period=events with onset from first dose to last dose plus 2 days.

9. Event Rate of Confirmed Major Bleeding or Clinically Relevant Non-Major Bleeding (CRNM) Using ISTH Criteria During the Treatment Period - Treated Participants [From first dose to first occurrence of event (ISTH major or CRNM bleed) during Treatment Period (first dose to last dose + 2 days), up to March 2011, approximately 2 years]

   ISTH Major bleed: acute clinically overt bleeding accompanied by one or more of the following: A decrease in Hgb of 2 g/dL or more over 24 hours; A transfusion of 2 or more units of packed RBCs; Bleeding that occurs in at least one of the following critical sites: intracranial, intraspinal, intraocular (within the corpus of the eye), pericardial, intra-articular, intramuscular with compartment syndrome, retroperitoneal; Bleeding that was fatal. CRNM: acute clinically overt bleeding that did not satisfy additional criteria required for the bleeding event to be defined as a major bleeding event and meets at least one of the following: Hospital admission for bleeding; Physician guided medical or surgical treatment for bleeding; Change in anti-thrombotic treatment (anticoagulant or antiplatelet) therapy. Bleeding events were adjudicated by the Adjudication Committee. Treatment Period=events with onset from first dose to last dose plus 2 days.

10. Event Rate of All Bleeding Reported by the Investigator During the Treatment Period - Treated Participants [From first dose to first occurrence of event (Bleeding) during Treatment Period (first dose to last dose + 2 days), up to March 2011, approximately 2 years]

    Bleeding events were adjudicated by the Adjudication Committee and classified according to Thrombolysis in Myocardial Infarction (TIMI) major, minor, minimal, and International Society on Thrombosis and Hemostasis (ISTH) major and clinically relevant non-major bleeding (CRNM) criteria. The adjudicated results based on TIMI and ISTH classifications, and programmatically identified events (not adjudicated) according to Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) classification were used in the analyses of bleeding endpoints. GUSTO Bleed Criteria included Severe or life-threatening: Intracranial hemorrhage, or bleeding that causes hemodynamic compromise requiring intervention; Moderate: Bleeding that requires a blood transfusion, but does not result in hemodynamic compromise; Mild: Bleeding that does not meet criteria for either severe or moderate bleeding. Treatment Period=events with onset from first dose to last dose plus 2 days.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Acute coronary syndrome (ACS)

• Clinically stable

• Receiving standard of care for ACS

Exclusion Criteria:

• Severe hypertension

• Active bleeding or high risk for major bleeding

• Hemoglobin < 9 g/dL

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Uab Medical Center	Birmingham	Alabama	United States	35294
2	University Of Alabama At Birmingham	Birmingham	Alabama	United States	35294
3	Heart Center Research, Llc	Huntsville	Alabama	United States	35801
4	North Phoenix Heart Center	Phoenix	Arizona	United States	85020
5	Sparks Regional Medical Center	Fort Smith	Arkansas	United States	72901
6	Nea Baptist Clinic	Jonesboro	Arkansas	United States	72401
7	Phase Care, Llc	Alameda	California	United States	94501
8	Cardiology Consultants Of Orange County	Anaheim	California	United States	92801
9	Beaver Medical Group	Banning	California	United States	92220
10	Local Institution	Chula Vista	California	United States	91911
11	Escondido Cardiology Associates, Inc.	Escondido	California	United States	92025
12	William D. Bowden, D.O.	Healdsburg	California	United States	95448
13	California Heart Specialists, Inc.	Huntington Beach	California	United States	92648
14	Caring Clinical Research Corporation	Laguna Hills	California	United States	92653
15	Eisenstein, Isaac	Lakewood	California	United States	90712
16	Arvind J. Mehta, Md	Long Beach	California	United States	90806
17	Local Institution	Los Alamitos	California	United States	90720
18	Preciado Cardiology Incorporated	Los Angeles	California	United States	90033
19	East Bay Physicians Medical Group	Oakland	California	United States	94609
20	St. Joseph Heritage Medical Group	Orange	California	United States	92868
21	A.R.I. Clinical Trials, Inc.	Redondo Beach	California	United States	90277
22	Coastal Multi-Specialty Research	Santa Ana	California	United States	92704
23	Radiant Research, Inc	Santa Rosa	California	United States	95405
24	Harbbor-Ucla Medical Center	Torrance	California	United States	90509
25	Rocky Mountain Cardiology	Boulder	Colorado	United States	80304
26	South Denver Cardiology Associates Pc	Littleton	Colorado	United States	80120
27	Drogue Medical, Llc	Wheat Ridge	Colorado	United States	80033
28	Hartford Hospital	Hartford	Connecticut	United States	06102
29	Alfieri Cardiology	Newark	Delaware	United States	19713
30	Orlando Heart Specialists	Altamonte Springs	Florida	United States	32714
31	Palm Beach Heart Institute, Llc	Atlantis	Florida	United States	33462
32	Ronald L. Walsh, Do	Clearwater	Florida	United States	33756
33	The Heart And Vascular Institute Of Florida	Clearwater	Florida	United States	33756
34	Cardiovascular Specialist Of South Florida	Davie	Florida	United States	33324
35	David E. Perloff, Md	Ft. Lauderdale	Florida	United States	33316
36	Nature Coast Clinical Research	Inverness	Florida	United States	34452
37	Jacksonville Heart Center, Pa	Jacksonville	Florida	United States	32207
38	Jacksonville Center For Clinical Research	Jacksonville	Florida	United States	32216
39	East Coast Institute For Research	Jacksonville	Florida	United States	32223
40	The Cardio Vascular Center P.A.	Lake Mary	Florida	United States	32746
41	Alpha Medical Research, Llc	Melbourne	Florida	United States	32901
42	Melbourne Internal Medicine Associates (Mima)	Melbourne	Florida	United States	32901
43	Mount Sinai Medical Center	Miami Beach	Florida	United States	33140
44	Glenn J. Barquet, Md	Miami	Florida	United States	33133
45	Miami Cardiology Clinical Research, L.L.C.	Miami	Florida	United States	33156
46	Advanced Pharma Clinical Research	Miami	Florida	United States	33175
47	Mediquest Research Group Inc.	Ocala	Florida	United States	34471
48	Ocala Research Institute, Inc	Ocala	Florida	United States	34471
49	Florida Heart Group	Orlando	Florida	United States	32803
50	Orlando Heart Center	Orlando	Florida	United States	32806
51	Palm Beach Gardens Research Center Llc	Palm Beach Gardens	Florida	United States	33410
52	Local Institution	Pembroke Pines	Florida	United States	33028
53	Cardiology Consultants	Pensacola	Florida	United States	32501
54	Advent Clinical Research Centers, Inc.	Pinellas Park	Florida	United States	33781
55	Cardio-Pulmonary Associates	Plantation	Florida	United States	33317
56	Avivo Clin Clinical Services	Port Orange	Florida	United States	32127
57	Heartcare Research	Sarasota	Florida	United States	34232
58	St. Augustine Cardiology Associates	St. Augustine	Florida	United States	32086
59	Dr Kiran C Patel Research Institute At Pepin Heart Hospital	Tampa	Florida	United States	33613
60	Howard T. Tee, M.D., F.A.C.P., F.A.C.C.	Vero Beach	Florida	United States	32960
61	Indian River Cardiovascular Associates, Inc	Vero Beach	Florida	United States	32960
62	Cardiology Partners Clinical Research Institute	Wellington	Florida	United States	33449
63	Cardiovascular Physicians Of North Atlanta	Atlanta	Georgia	United States	30342
64	Medical College Of Georgia	Augusta	Georgia	United States	30912
65	Columbus Cardiology Associates Pc	Columbus	Georgia	United States	31909
66	Georgia Heart Specialists	Covington	Georgia	United States	30014
67	Atlanta Institute For Medical Research, Inc	Decatur	Georgia	United States	30030
68	In-Quest Medical Research, Llc	Duluth	Georgia	United States	30096
69	Alta Pharmaceutical Research Center, Inc.	Dunwoody	Georgia	United States	30338
70	North Georgia Medical Research	Ellijay	Georgia	United States	30540
71	Northeast Georgia Heart Cntr, Pc	Gainesville	Georgia	United States	30501
72	Mercer University School Of Medicine	Macon	Georgia	United States	31201
73	Well Star Cardiovascular Medicine, Pc	Marietta	Georgia	United States	30060
74	Southern Heart Research Institute, Llc	Riverdale	Georgia	United States	30274
75	Memorial Hospital Of Carbondale	Carbondale	Illinois	United States	62901
76	Northwestern University	Chicago	Illinois	United States	60611
77	Rush University Medical Center	Chicago	Illinois	United States	60612
78	University Of Chicago Hospitals	Chicago	Illinois	United States	60637
79	Clinical Investigation Specialists, Inc	Gurnee	Illinois	United States	60031
80	Gateway Cardiology. P.C	Jerseyville	Illinois	United States	62052
81	Midwest Heart Foundation	Lombard	Illinois	United States	60148
82	Local Institution	Moline	Illinois	United States	61265
83	Illinois Heart & Lung Research	Normal	Illinois	United States	61761
84	Heartcare Midwest	Peoria	Illinois	United States	61614
85	Elkhart Clinic, Llc	Elkhart	Indiana	United States	46514
86	St Margaret Mercy Healthcare Centers	Hammond	Indiana	United States	46320
87	Krannertt Institute Of Cardiology	Indianapolis	Indiana	United States	46202
88	R. L.Roudebush Va Medical Center	Indianapolis	Indiana	United States	46202
89	The Care Group, Llc	Indianapolis	Indiana	United States	46260
90	Medical Consultants, Pc	Muncie	Indiana	United States	47303
91	Local Institution	Valparaiso	Indiana	United States	46383
92	Mcfarland Clinic Pc	Ames	Iowa	United States	50010
93	Iowa Heart Center	West Des Moines	Iowa	United States	50266
94	Midwest Cardiology Associates , P.C.	Overland Park	Kansas	United States	66209
95	Kentucky Heart & Vascular Physicians	Ashland	Kentucky	United States	41101
96	Local Institution	Hazard	Kentucky	United States	41701
97	Cardiovascular Associates, Psc	Louisville	Kentucky	United States	40205
98	Research Integrity, Llc	Owensboro	Kentucky	United States	42303
99	Alexandria Cardiology Clinic	Alexandria	Louisiana	United States	71301
100	Clinical Research Network	Alexandria	Louisiana	United States	71301
101	Tulane University Hospital And Clinic	New Orleans	Louisiana	United States	70112
102	Overton Brooks V.A.M.C.	Shreveport	Louisiana	United States	71101
103	Louisiana State University Health Sciences Center-Shreveport	Shreveport	Louisiana	United States	71103
104	Louisiana Heart Center	Slidell	Louisiana	United States	70458
105	Local Institution	Annapolis	Maryland	United States	21401
106	Delmarva Heart Research Foundation	Salisbury	Maryland	United States	21804
107	Peninsula Cardiology Associates, P.A.	Salisbury	Maryland	United States	21804
108	Endeavor Medical Research, Plc	Alpena	Michigan	United States	49707
109	Henry Ford Hospital	Detroit	Michigan	United States	48202
110	Local Institution	Detroit	Michigan	United States	48236
111	Genesys Regional Medical Center	Grand Blanc	Michigan	United States	48439
112	Thoracic And Cardiovascular Healthcare Foundation	Lansing	Michigan	United States	48910
113	Local Institution	Mt. Pleasant	Michigan	United States	48858
114	Covenant Medical Center, Inc	Saginaw	Michigan	United States	48602
115	Great Lakes Heart & Vascular Institute, Pc	St. Joseph	Michigan	United States	49085
116	William Beaumont Hospital-Troy	Troy	Michigan	United States	48098
117	Hennepin County Medical Center	Minneapolis	Minnesota	United States	55415
118	Va Medical Center	Minneapolis	Minnesota	United States	55417
119	University Of Minnesota, Medical School	Minneapolis	Minnesota	United States	55455
120	St Cloud Hospital	St. Cloud	Minnesota	United States	56303
121	University Of Mississippi Medical Center	Jackson	Mississippi	United States	39216
122	Local Institution	Jackson	Mississippi	United States	49201
123	Missouri Cardiovascular Specialists	Columbia	Missouri	United States	65201
124	Washington University School Of Medicine	St. Louis	Missouri	United States	63110
125	Gateway Cardiology, P.C.	St. Louis	Missouri	United States	63128
126	Bryanlgh Heart Institute	Lincoln	Nebraska	United States	68506
127	Heart Consultants	Omaha	Nebraska	United States	68114
128	Alegent Health Clinic Heart & Vascular Specialists	Omaha	Nebraska	United States	68124
129	Local Institution	Brick	New Jersey	United States	08723
130	Central Jersey Medical Research Center	Elizabeth	New Jersey	United States	07202
131	Hamilton Cardiology Associates	Hamilton	New Jersey	United States	08690
132	Local Institution	Linden	New Jersey	United States	07036
133	The Valley Hospital	Ridgewood	New Jersey	United States	07450
134	Central New Jersey Cardiology	South Plainfield	New Jersey	United States	07080
135	New York Methodist Hospital	Brooklyn	New York	United States	11215
136	Buffalo General Hospital	Buffalo	New York	United States	14203
137	Dr. Michael Sacher	Massapequa	New York	United States	11758
138	Hudson Valley Heart Center	Poughkeepsie	New York	United States	12601
139	Asheville Cardiology Associates	Asheville	North Carolina	United States	28803
140	The University Of North Carolina At Chapel Hill	Chapel Hill	North Carolina	United States	27599
141	Duke University Medical Center	Durham	North Carolina	United States	27710
142	East Carolina Heart Institute At East Carolina University	Greenville	North Carolina	United States	27834
143	Wake Med Heart Center	Raleigh	North Carolina	United States	27610
144	Wilmington Medical Research	Wilmington	North Carolina	United States	28401
145	Azalea Research Center	Wilmington	North Carolina	United States	28403
146	Local Institution	Fargo	North Dakota	United States	58122
147	Otfried N. Niedermaier, Md	Akron	Ohio	United States	44304
148	City Cardiology Associates	Barberton	Ohio	United States	44203
149	Cincinnati Veterans Affairs Medical Center	Cincinnati	Ohio	United States	45220
150	Fairfield Cardiac Cath Lab, Llc	Fairfield	Ohio	United States	45014
151	Genoa Medical Center	Genoa	Ohio	United States	43430
152	Middletown Cardiovascular Associates	Middletown	Ohio	United States	45044
153	Toledo Cardiology Consultants	Toledo	Ohio	United States	43608
154	Local Institution	Youngstown	Ohio	United States	44501
155	Cardiology Associates Of Southeastern Ohio	Zanesville	Ohio	United States	43701
156	Blue Stem Cardiology	Bartlesville	Oklahoma	United States	74006
157	Cor Clinical Research, Llc	Oklahoma City	Oklahoma	United States	73103
158	University Of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
159	Oklahoma Cardiovascular Associates	Oklahoma City	Oklahoma	United States	73109
160	St. Charles Health System, Inc.	Bend	Oregon	United States	97701
161	Portland Preventive Cardiology, L.L.C.	Portland	Oregon	United States	97225
162	Blair Medical Associates, Inc.	Altoona	Pennsylvania	United States	16602
163	St. Lukes Cardiology Associates	Bethlehem	Pennsylvania	United States	18018
164	Consultants In Cardiovascular Diseases, Inc.	Erie	Pennsylvania	United States	16502
165	Hamot Medical Center	Erie	Pennsylvania	United States	16507
166	Richard M. Kastelic M.D. & Associates, P.C.	Johnstown	Pennsylvania	United States	15905
167	The Heart Group	Lancaster	Pennsylvania	United States	17603
168	Drexel University College Of Medicine	Philadelphia	Pennsylvania	United States	19102
169	Penn Presbyterian Medical Center	Philadelphia	Pennsylvania	United States	19104
170	Pennsylvania Cardiology Associates	Philadelphia	Pennsylvania	United States	19106
171	Va Pittsburgh Healthcare System	Pittsburgh	Pennsylvania	United States	15240
172	Pottstown Medical Specialists, Inc	Pottstown	Pennsylvania	United States	19464
173	Local Institution	Scranton	Pennsylvania	United States	18508
174	Buxmont Cardiology Associates, Pc	Sellersville	Pennsylvania	United States	18960
175	Moffit Heart & Vascular Group	Wormleysburg	Pennsylvania	United States	17043
176	The Miriam Hospital	Providence	Rhode Island	United States	02906
177	Anmed Health	Anderson	South Carolina	United States	29621
178	Carl Wilson Sofley, Jr., Md	Anderson	South Carolina	United States	29621
179	Lowcountry Medical Group	Beaufort	South Carolina	United States	29906
180	Columbia Cardiology	Columbia	South Carolina	United States	29204
181	Cardiology Assoicates, Pc/Black Hills Clinical Research Ctr	Rapid City	South Dakota	United States	57701
182	North Central Heart Institute	Sioux Falls	South Dakota	United States	57108
183	The Chattanooga Heart Institute	Chattanooga	Tennessee	United States	37404
184	The Stern Cardiovascular Center, Pa	Germantown	Tennessee	United States	38138
185	Research Associates Of Jackson	Jackson	Tennessee	United States	38301
186	Mountain State Health Alliance	Johnson City	Tennessee	United States	37604
187	Knoxville Heart Group	Knoxville	Tennessee	United States	37916
188	Access Clinical Trials	Nashville	Tennessee	United States	37203
189	Parkway Cardiology Associates, Pc	Oak Ridge	Tennessee	United States	37830
190	Amarillo Heart Clinical Research Institute Inc.	Amarillo	Texas	United States	79106
191	Dallas Va Medical Center	Dallas	Texas	United States	75216
192	Cardiovascular Research Institute Of Dallas	Dallas	Texas	United States	75231
193	Heart Consultants Of North Texas	Dallas	Texas	United States	75231
194	Texas Health Research & Education Institute	Fort Worth	Texas	United States	76104
195	T&R Clinic	Fort Worth	Texas	United States	76117
196	Med Tech, Inc.	Houston	Texas	United States	77024
197	Methodist Debakey Heart & Vascular Center	Houston	Texas	United States	77030
198	Centex Research, Pineloch Medical Clinic	Houston	Texas	United States	77062
199	Heart Care Center	Houston	Texas	United States	77070
200	Northwest Houston Cardiology, Pa	Houston	Texas	United States	77070
201	Texas Cardiac Center	Lubbock	Texas	United States	79410
202	Central Cardiovascular Institute Of San Antonio	San Antonio	Texas	United States	78201
203	Jose A. Perez, M.D.	San Antonio	Texas	United States	78201
204	S.A.M. Clinical Research Center	San Antonio	Texas	United States	78229
205	Sugarland Cardiology Associates	Sugarland	Texas	United States	77479
206	Scott&White Memorial Hospital	Temple	Texas	United States	76508
207	Northwest Heart Center	Tomball	Texas	United States	77375
208	Tyler Cardiovascular Consultants	Tyler	Texas	United States	75701
209	Utah Cardiology P.C	Layton	Utah	United States	84041
210	Bermisa Family Practice & Research Center	Chesapeake	Virginia	United States	23321
211	Zakhary, Bosh	Danville	Virginia	United States	24541
212	Heart Care Associates P.C.	Hopewell	Virginia	United States	23860
213	The Cardiology Group Centra.	Lynchburg	Virginia	United States	24501
214	Virginia Cardiolovascular Associates	Manassas	Virginia	United States	20109
215	Local Institution	Midlothian	Virginia	United States	23114
216	Sendara Cardiovasular Research Institute	Norfolk	Virginia	United States	23507
217	Virgina Commonwealth Universitymedical Center	Richmond	Virginia	United States	23298
218	Inland Cardiology Associates	Spokane	Washington	United States	99204
219	Franciscan Research Center	Tacoma	Washington	United States	98405
220	Dean And St. Mary'S Outpatient Center	Madison	Wisconsin	United States	53715
221	Wheaton Franciscan Healthcare St. Joseph	Milwaukee	Wisconsin	United States	53210
222	Local Institution	Berazategui	Buenos Aires	Argentina	B1884KZB
223	Local Institution	Capital Federal	Buenos Aires	Argentina	1155
224	Local Institution	Ciudad Autonoma Buenos Aires	Buenos Aires	Argentina	1180
225	Local Institution	Ciudad Autonoma De Beunos Aire	Buenos Aires	Argentina	1431
226	Local Institution	Coronel Suarez	Buenos Aires	Argentina	7540
227	Local Institution	Gaba	Buenos Aires	Argentina	1437
228	Local Institution	Haedo	Buenos Aires	Argentina	B1706AJU
229	Local Institution	Junin	Buenos Aires	Argentina	6000
230	Local Institution	La Plata	Buenos Aires	Argentina	B1902COS
231	Local Institution	Lanus Oeste	Buenos Aires	Argentina	1824
232	Local Institution	Moron	Buenos Aires	Argentina	1708
233	Local Institution	Quilmes	Buenos Aires	Argentina	B1878DKF
234	Local Institution	Ramos Mejia	Buenos Aires	Argentina	B1704ETD
235	Local Institution	San Isidro	Buenos Aires	Argentina	1642
236	Local Institution	San Martin	Buenos Aires	Argentina	B1650CSQ
237	Local Institution	Resistencia	Chaco	Argentina	3500
238	Local Institution	Villa Cabrera	Cordoba	Argentina	5009
239	Local Institution	Villa Carlos Paz	Cordoba	Argentina	5152
240	Local Institution	Villa Maria	Cordoba	Argentina	5900
241	Local Institution	Corrientes Capital	Corrientes	Argentina	3400
242	Local Institution	San Salvador De Jujuy	Jujuy	Argentina	Y4600ABF
243	Local Institution	Capital	Mendoza	Argentina	5500
244	Local Institution	Posadas	Misiones	Argentina	3300
245	Local Institution	Cipolletti	Rio Negro	Argentina	8324
246	Local Institution	Rosario	Santa Fe	Argentina	2000
247	Local Institution	Rosario	Santa Fe	Argentina	2002
248	Local Institution	San Miguel De Tucuman	Tucuman	Argentina	4000
249	Local Institution	San Miguel De Tucuman	Tucuman	Argentina	T4000ICL
250	Local Institution	Buenos Aires		Argentina	1039
251	Local Institution	Buenos Aires		Argentina	1119
252	Local Institution	Buenos Aires		Argentina	1122
253	Local Institution	Buenos Aires		Argentina	1280
254	Local Institution	Buenos Aires		Argentina	1428
255	Local Institution	Cordoba		Argentina	5000
256	Local Institution	Cordoba		Argentina	5002
257	Local Institution	Cordoba		Argentina	5006
258	Local Institution	Cordoba		Argentina	X5004CDT
259	Local Institution	Corrientes		Argentina	3400
260	Local Institution	Salta		Argentina	A4400ANG
261	Local Institution	San Luis		Argentina	D5702JRS
262	Local Institution	Santa Fe		Argentina	3000
263	Local Institution	Santa Fe		Argentina	S3000AZG
264	Local Institution	Bruce	Australian Capital Territory	Australia	2617
265	Local Institution	Broken Hill	New South Wales	Australia	2880
266	Local Institution	Kogarah	New South Wales	Australia	2217
267	Local Institution	Lismore	New South Wales	Australia	2480
268	Local Institution	Cairns	Queensland	Australia	4870
269	Local Institution	Herston	Queensland	Australia	4031
270	Local Institution	Milton	Queensland	Australia	4064
271	Local Institution	Ashford	South Australia	Australia	5035
272	Local Institution	Elizabeth Vale	South Australia	Australia	5112
273	Local Institution	Woodville	South Australia	Australia	5011
274	Local Institution	Fitzroy	Victoria	Australia	3065
275	Local Institution	Geelong	Victoria	Australia	3220
276	Local Institution	Richmond	Victoria	Australia	3121
277	Local Institution	Feldkirch		Austria	6800
278	Local Institution	Graz		Austria	8036
279	Local Institution	Linz		Austria	4020
280	Local Institution	Oberpullendorf		Austria	7350
281	Local Institution	Vienna		Austria	1030
282	Local Institution	Vienna		Austria	1090
283	Local Institution	Wien		Austria	1090
284	Local Institution	Wien		Austria	1160
285	Local Institution	Wien		Austria	1220
286	Local Institution	Aalst		Belgium	9300
287	Local Institution	Anderlecht		Belgium	1070
288	Local Institution	Antwerpen		Belgium	2060
289	Local Institution	Bonheiden		Belgium	2820
290	Local Institution	Brasschaat		Belgium	2930
291	Local Institution	Brugge		Belgium	8000
292	Local Institution	Gent		Belgium	9000
293	Local Institution	Huy		Belgium	4500
294	Local Institution	Ieper		Belgium	8900
295	Local Institution	Mechelen		Belgium	2800
296	Local Institution	Mol		Belgium	2400
297	Local Institution	Yvoir		Belgium	5530
298	Local Institution	Maceio	Alagoas	Brazil	57051
299	Local Institution	Salvador	Bahia	Brazil	40144
300	Local Institution	Salvador	Bahia	Brazil	40323
301	Local Institution	Salvador	Bahia	Brazil	41148
302	Local Institution	Salvador	Bahia	Brazil	41810
303	Local Institution	Sobral	Ceara	Brazil	62041
304	Local Institution	Brasilia	Distrito Federal	Brazil	70335
305	Local Institution	Brasilia	Distrito Federal	Brazil	70390
306	Local Institution	Brasilia	Distrito Federal	Brazil	70658
307	Local Institution	Brasilia	Distrito Federal	Brazil	72115
308	Local Institution	Goiania	Goias	Brazil	74809
309	Local Institution	Goiania	Goias	Brazil	74823
310	Local Institution	Juiz De Fora	Mato Grosso	Brazil	36021
311	Local Institution	Belo Horizonte	Minas Gerais	Brazil	30110
312	Local Institution	Belo Horzonte	Minas Gerais	Brazil	30150
313	Local Institution	Uberlandia	Minas Gerais	Brazil	384000-368
314	Local Institution	Uberlandia	Minas Gerais	Brazil	38400
315	Local Institution	Curitiba	Parana	Brazil	80010
316	Local Institution	Curitiba	Parana	Brazil	80320
317	Local Institution	Curitiba	Parana	Brazil	80730
318	Local Institution	Londrina	Parana	Brazil	86010
319	Local Institution	Belem	Para	Brazil	66087
320	Local Institution	Recife	Pernambuco	Brazil	50100
321	Local Institution	Rio Janeiro	Rio De Janeiro	Brazil	22280
322	Local Institution	Natal	Rio Grande Do Norte	Brazil	59020
323	Local Institution	Passo Fundo	Rio Grande Do Sul	Brazil	99010
324	Local Institution	Porto Alegre	Rio Grande Do Sul	Brazil	90020
325	Local Institution	Porto Alegre	Rio Grande Do Sul	Brazil	90035
326	Local Institution	Porto Alegre	Rio Grande Do Sul	Brazil	90110
327	Local Institution	Porto Alegre	Rio Grande Do Sul	Brazil	90610
328	Local Institution	Porto Alegre	Rio Grande Do Sul	Brazil	90620
329	Local Institution	Porto Alegre	Rio Grande Do Sul	Brazil	91350
330	Local Institution	Blumenau	Santa Catarina	Brazil	89010
331	Local Institution	Sao Jose	Santa Catarina	Brazil	88103
332	Local Institution	Campinas	Sao Paulo	Brazil	13059
333	Local Institution	Limeira	Sao Paulo	Brazil	13480
334	Local Institution	Marilia	Sao Paulo	Brazil	17515
335	Local Institution	Marilia	Sao Paulo	Brazil	17519
336	Local Institution	Santo Andre	Sao Paulo	Brazil	09020
337	Local Institution	Santo Andre	Sao Paulo	Brazil	09190
338	Local Institution	Sao Caetano Do Sul	Sao Paulo	Brazil	09540
339	Local Institution	Sao Jose Do Rio Preto	Sao Paulo	Brazil	15015
340	Local Institution	Sao Jose Do Rio Preto	Sao Paulo	Brazil	15090
341	Local Institution	Rio De Janeiro		Brazil	22031
342	Local Institution	Rio De Janeiro		Brazil	22240
343	Local Institution	Rio De Janeiro		Brazil	22261
344	Local Institution	Sao Paulo		Brazil	01323
345	Local Institution	Sao Paulo		Brazil	01506
346	Local Institution	Sao Paulo		Brazil	02276
347	Local Institution	Sao Paulo		Brazil	04012
348	Local Institution	Sao Paulo		Brazil	04023
349	Local Institution	Sao Paulo		Brazil	05403
350	Local Institution	Sao Paulo		Brazil	05508
351	Local Institution	Burgas		Bulgaria	8000
352	Local Institution	Dimitrovgrad		Bulgaria	6400
353	Local Institution	Pazardzhik		Bulgaria	4400
354	Local Institution	Pleven		Bulgaria	5800
355	Local Institution	Plovdiv		Bulgaria	4000
356	Local Institution	Plovdiv		Bulgaria	4002
357	Local Institution	Sofia		Bulgaria	1142
358	Local Institution	Sofia		Bulgaria	1202
359	Local Institution	Sofia		Bulgaria	1233
360	Local Institution	Sofia		Bulgaria	1309
361	Local Institution	Sofia		Bulgaria	1407
362	Local Institution	Sofia		Bulgaria	1431
363	Local Institution	Sofia		Bulgaria	1527
364	Local Institution	Sofia		Bulgaria	1606
365	Local Institution	Sofia		Bulgaria	1618
366	Local Institution	Stara Zagora		Bulgaria	6003
367	Local Institution	Varna		Bulgaria	9010
368	Local Institution	Edmonton	Alberta	Canada	T5H 3V9
369	Local Institution	Edmonton	Alberta	Canada	T6G 2B7
370	Local Institution	Edmonton	Alberta	Canada	T6K 4C1
371	Local Institution	New Westminster	British Columbia	Canada	V3L 3W5
372	Local Institution	Penticton	British Columbia	Canada	V2A 3G6
373	Local Institution	Victoria	British Columbia	Canada	V8R 4R2
374	Local Institution	Winnipeg	Manitoba	Canada	R3K 0Y8
375	Local Institution	St-John	Newfoundland and Labrador	Canada	A1B 3V6
376	Local Institution	Halifax	Nova Scotia	Canada	B3H 3A7
377	Local Institution	Sydney	Nova Scotia	Canada	B1P 1P3
378	Local Institution	Cambridge	Ontario	Canada	N1R 6V6
379	Local Institution	Cambridge	Ontario	Canada	N1R 7R1
380	Local Institution	Grimsby	Ontario	Canada	L3M 1P3
381	Local Institution	Kitchener	Ontario	Canada	N2M 1B2
382	Local Institution	London	Ontario	Canada	N6A 5A5
383	Local Institution	Oshawa	Ontario	Canada	L1H 1B9
384	Local Institution	Oshawa	Ontario	Canada	L1H 7K4
385	Local Institution	Oshawa	Ontario	Canada	L1J2K1
386	Local Institution	Parry Sound	Ontario	Canada	P2A 3A4
387	Local Institution	Sarnia	Ontario	Canada	N7T 4R9
388	Local Institution	Scarborough	Ontario	Canada	M1E 4B9
389	Local Institution	Scarborough	Ontario	Canada	M1P 2T7
390	Local Institution	Sudbury	Ontario	Canada	P3C 5K7
391	Local Institution	Sudbury	Ontario	Canada	P3E 2N8
392	Local Institution	Sudbury	Ontario	Canada	P3E 3B8
393	Local Institution	Toronto	Ontario	Canada	M4C 3E7
394	Local Institution	Toronto	Ontario	Canada	M5B 1W8
395	Local Institution	Toronto	Ontario	Canada	M5G 2C4
396	Local Institution	Windsor	Ontario	Canada	N8X 1L9
397	Local Institution	Chiccutimi	Quebec	Canada	G7H 5H6
398	Local Institution	Levis	Quebec	Canada	G6V 3Z1
399	Local Institution	Montreal	Quebec	Canada	H3A 1A1
400	Local Institution	Sorel-Tracy	Quebec	Canada	J3P1N5
401	Local Institution	St-Foy	Quebec	Canada	G1V 4G5
402	Local Institution	St. Charles Borromee	Quebec	Canada	J6E 6J2
403	Local Institution	St. Jerome	Quebec	Canada	J7Z 5T3
404	Local Institution	Terrebonne	Quebec	Canada	J6V 2H2
405	Local Institution	Temuco	Araucania	Chile	4781176
406	Local Institution	Concepcion	Biobio	Chile	4070038
407	Local Institution	Talcahuano	Biobio	Chile	4270918
408	Local Institution	Osorno	Los Lagos	Chile	5311089
409	Local Institution	Punta Arenas	Magallanes Antartica	Chile	6212296
410	Local Institution	Santiago	Metropolitana	Chile	6510031
411	Local Institution	Santiago	Metropolitana	Chile	7650018
412	Local Institution	Santiago	Metropolitana	Chile	8053095
413	Local Institution	Santiago	Metropolitana	Chile	8380000
414	Local Institution	Santiago	Metropolitana	Chile
415	Local Institution	Vina Del Mar	Valparaiso	Chile	2570017
416	Local Institution	Puerto Montt		Chile
417	Local Institution	Beijing	Beijing	China	100020
418	Local Institution	Beijing	Beijing	China	100029
419	Local Institution	Beijing	Beijing	China	100034
420	Local Institution	Beijing	Beijing	China	100038
421	Local Institution	Beijing	Beijing	China	100044
422	Local Institution	Beijing	Beijing	China	100088
423	Local Institution	Beijing	Beijing	China	100176
424	Local Institution	Beijing	Beijing	China	100730
425	Local Institution	Chongqing	Chongqing	China	400042
426	Local Institution	Lanzhou	Gansu	China	730030
427	Local Institution	Guangzhou	Guangdong	China	510010
428	Local Institution	Guangzhou	Guangdong	China	510080
429	Local Institution	Guangzhou	Guangdong	China	510120
430	Local Institution	Guangzhou	Guangdong	China	510180
431	Local Institution	Nanning	Guangxi	China	530021
432	Local Institution	Shijiazhuang	Hebei	China	710061
433	Local Institution	Harbin	Heilongjiang	China	150001
434	Local Institution	Wuhan	Hubei	China	430060
435	Local Institution	Changsha	Hunan	China	410005
436	Local Institution	Nanjing	Jiangsu	China	210008
437	Local Institution	Nanjing	Jiangsu	China	210009
438	Local Institution	Nanjing	Jiangsu	China	210029
439	Local Institution	Suzhou	Jiangsu	China	215004
440	Local Institution	Suzhou	Jiangsu	China	215006
441	Local Institution	Nanchang	Jiangxi	China	330006
442	Local Institution	Changchun	Jilin	China	130021
443	Local Institution	Changchun	Jilin	China	130041
444	Local Institution	Dalian	Liaoning	China	116023
445	Local Institution	Shenyang	Liaoning	China	110001
446	Local Institution	Shenyang	Liaoning	China	110004
447	Local Institution	Shenyang	Liaoning	China	110016
448	Local Institution	Jinan	Shandong	China	250012
449	Local Institution	Beijing	Shanghai	China	100037
450	Local Institution	Shanghai	Shanghai	China	200003
451	Local Institution	Shanghai	Shanghai	China	200065
452	Local Institution	Shanghai	Shanghai	China	200072
453	Local Institution	Chengdu	Sichuan	China	610041
454	Local Institution	Chongqing	Sichuan	China	400010
455	Local Institution	Kunming	Yunnan	China	650101
456	Local Institution	Hangzhou	Zhejiang	China	310009
457	Local Institution	Hangzhou	Zhejiang	China	310016
458	Local Institution	Xian		China	710061
459	Local Institution	Cartagena	Bolivar	Colombia
460	Local Institution	Bogota	Cundinamaral	Colombia
461	Local Institution	Cali	Valle	Colombia
462	Local Institution	Barranquilla		Colombia
463	Local Institution	Bogota		Colombia
464	Local Institution	Floridablanca		Colombia
465	Local Institution	Manizales		Colombia
466	Local Institution	Medelin		Colombia
467	Local Institution	Medellin		Colombia
468	Local Institution	Brno		Czech Republic	625 00
469	Local Institution	Hradec Kralove		Czech Republic	500 05
470	Local Institution	Liberec		Czech Republic	460 63
471	Local Institution	Novy Jicin		Czech Republic	741 01
472	Local Institution	Olomouc		Czech Republic	77520
473	Local Institution	Ostrava		Czech Republic	728 80
474	Local Institution	Praha 10		Czech Republic	100 34
475	Local Institution	Rakovnik		Czech Republic	269 29
476	Local Institution	Usti Nad Orlici		Czech Republic	562 18
477	Local Institution	Arhus C		Denmark	8000
478	Local Institution	Copenhagen		Denmark	2100
479	Local Institution	Copenhagen		Denmark	2300
480	Local Institution	Copenhagen		Denmark	2400
481	Local Institution	Esbjerg		Denmark	6700
482	Local Institution	Haderslev		Denmark	6100
483	Local Institution	Hellerup		Denmark	2900
484	Local Institution	Hillerod		Denmark	3400
485	Local Institution	Hvidovre		Denmark	2650
486	Local Institution	Naestved		Denmark	4700
487	Local Institution	Silkeborg		Denmark	8600
488	Local Institution	Slagelse		Denmark	4200
489	Local Institution	Espoo		Finland	02740
490	Local Institution	Helsinki		Finland	00029
491	Local Institution	Rovaniemi		Finland	96101
492	Local Institution	Tampere		Finland	33520
493	Local Institution	Albi Cedex 09		France	81013
494	Local Institution	Amiens Cedex 1		France	80054
495	Local Institution	Avignon		France	84082
496	Local Institution	Cholet		France	49325
497	Local Institution	Lagny Sur Marne		France	77405
498	Local Institution	Langres Cedex		France	52206
499	Local Institution	Montpellier		France	34000
500	Local Institution	Paris Cedex 13		France	76561
501	Local Institution	Pau Universite Cedex		France	64046
502	Local Institution	Strasbourg Cedex		France	67091
503	Local Institution	Toulouse Cedex 03		France	31076
504	Local Institution	Bad Berka		Germany	99437
505	Local Institution	Bad Nauheim		Germany	61231
506	Local Institution	Berlin		Germany	12351
507	Local Institution	Berlin		Germany	12559
508	Local Institution	Berlin		Germany	13509
509	Local Institution	Berlin		Germany	13585
510	Local Institution	Bernau		Germany	16321
511	Local Institution	Bonn		Germany	53105
512	Local Institution	Bonn		Germany	53115
513	Local Institution	Chemnitz		Germany	09111
514	Local Institution	Coswig		Germany	06869
515	Local Institution	Cottbus		Germany	03048
516	Local Institution	Dachau		Germany	85221
517	Local Institution	Essen		Germany	45122
518	Local Institution	Flensburg		Germany	24939
519	Local Institution	Halle/Saale		Germany	06120
520	Local Institution	Hamburg		Germany	20099
521	Local Institution	Hamburg		Germany	21075
522	Local Institution	Hamburg		Germany	22763
523	Local Institution	Hoyerswerda		Germany	02977
524	Local Institution	Jena		Germany	07747
525	Local Institution	Leverkusen		Germany	51375
526	Local Institution	Limburg		Germany	65549
527	Local Institution	Luebeck		Germany	23538
528	Local Institution	Mainz		Germany	55131
529	Local Institution	Muenster		Germany	48149
530	Local Institution	Neuss		Germany	41464
531	Local Institution	Paderborn		Germany	33098
532	Local Institution	Pirna		Germany	01796
533	Local Institution	Regensburg		Germany	93053
534	Local Institution	Rostock		Germany	18057
535	Local Institution	Wesel		Germany	46483
536	Local Institution	Baja		Hungary	6500
537	Local Institution	Balatonfured		Hungary	8230
538	Local Institution	Budapest		Hungary	1027
539	Local Institution	Budapest		Hungary	1032
540	Local Institution	Budapest		Hungary	1041
541	Local Institution	Budapest		Hungary	1085
542	Local Institution	Budapest		Hungary	1096
543	Local Institution	Budapest		Hungary	1097
544	Local Institution	Budapest		Hungary	1106
545	Local Institution	Budapest		Hungary	1145
546	Local Institution	Budpest		Hungary	1122
547	Local Institution	Cegled		Hungary	2700
548	Local Institution	Debrecen		Hungary	4032
549	Local Institution	Dunaujvaros		Hungary	2400
550	Local Institution	Hodmezovasarhely		Hungary	6800
551	Local Institution	Kecskemet		Hungary	6000
552	Local Institution	Miskolc		Hungary	3526
553	Local Institution	Miskolc		Hungary	3529
554	Local Institution	Szekesfehervar		Hungary	8000
555	Local Institution	Szekszard		Hungary	7100
556	Local Institution	Szentes		Hungary	6600
557	Local Institution	Szombathely		Hungary	9700
558	Local Institution	Zalaegerszeg		Hungary	8900
559	Local Institution	Hyderabad	Andhra Pradesh	India	500-012
560	Local Institution	Hyderabad	Andhra Pradesh	India	500063
561	Local Institution	Vijayawada	Andhra Pradesh	India	520008
562	Local Institution	Ahmedabad	Gujarat	India	380006
563	Local Institution	Ahmedabad	Gujarat	India	380014
564	Local Institution	Ahmedabad	Gujarat	India	380015
565	Local Institution	Vadodara	Gujarat	India	390007
566	Local Institution	Gurgaon	Haryana	India	122001
567	Local Institution	Bangalore	Karnataka	India	560 099
568	Local Institution	Bangalore	Karnataka	India	560054
569	Local Institution	Mysore	Karnataka	India	570020
570	Local Institution	Shivamogga	Karnataka	India	577201
571	Local Institution	Indore	Madhya Pradesh	India	452008
572	Local Institution	Mumbai	Maharashtra	India	400007
573	Local Institution	Mumbai	Maharashtra	India	400050
574	Local Institution	Nagpur	Maharashtra	India	440010
575	Local Institution	Nagpur	Maharashtra	India	440012
576	Local Institution	Nagpur	Maharashtra	India	440033
577	Local Institution	Pune	Maharashtra	India	411001
578	Local Institution	Pune	Maharastra	India	411004
579	Local Institution	Jalandhar	Punjab	India	144008
580	Local Institution	Jaipur	Rajasthan	India	302001
581	Local Institution	Jaipur	Rajasthan	India	302004
582	Local Institution	Jaipur	Rajasthan	India	302017
583	Local Institution	Coimbatore	Tamil Nadu	India	641037
584	Local Institution	Chennai	Tamilnadu	India	600081
585	Local Institution	Lucknow	Uttar Pradesh	India	226003
586	Local Institution	Bangalore, Karnataka		India	560034
587	Local Institution	Bikaner		India	334001
588	Local Institution	Mangalore		India	575003
589	Local Institution	New Delhi		India	110025
590	Local Institution	New Delhi		India	110060
591	Local Institution	Pune		India	411004
592	Local Institution	Afula		Israel	18101
593	Local Institution	Ashkelon		Israel	78306
594	Local Institution	Hadera		Israel	38100
595	Local Institution	Haifa		Israel	31048
596	Local Institution	Haifa		Israel	31096
597	Local Institution	Haifa		Israel	34362
598	Local Institution	Jerusalem		Israel	91004
599	Local Institution	Jerusalem		Israel	91031
600	Local Institution	Jerusalem		Israel	91120
601	Local Institution	Jerusalem		Israel	91240
602	Local Institution	Kfar-Saba		Israel	44281
603	Local Institution	Nahariya		Israel	22100
604	Local Institution	Nazareth		Israel	16000
605	Local Institution	Nazareth		Israel	16100
606	Local Institution	Petach Tikva		Israel	49100
607	Local Institution	Rehovot		Israel	76100
608	Local Institution	Safed		Israel	13100
609	Local Institution	Tel Aviv		Israel	64239
610	Local Institution	Tiberias		Israel	15208
611	Local Institution	Ascoli Piceno		Italy	63100
612	Local Institution	Bergamo		Italy	24128
613	Local Institution	Chieti		Italy	66013
614	Local Institution	Foggia		Italy	71100
615	Local Institution	Gravedona (Co)		Italy	22015
616	Local Institution	Grosseto		Italy	58100
617	Local Institution	Massa		Italy	54100
618	Local Institution	Milano		Italy	20132
619	Local Institution	Milan		Italy	20138
620	Local Institution	Naples		Italy	80131
621	Local Institution	Novara		Italy	28100
622	Local Institution	Pavia		Italy	27100
623	Local Institution	Perugia		Italy	06126
624	Local Institution	Roma		Italy	00184
625	Local Institution	San Daniele Del Friuli (Udine)		Italy	33038
626	Local Institution	Saronno (Va)		Italy	21047
627	Local Institution	Verona		Italy	37126
628	Local Institution	Nagoya-Shi	Aichi	Japan	4600001
629	Local Institution	Nagoya	Aichi	Japan	4538511
630	Local Institution	Nagoya	Aichi	Japan	455-8530
631	Local Institution	Nagoya	Aichi	Japan	4668650
632	Local Institution	Seto-Shi	Aichi	Japan	4898642
633	Local Institution	Matsudo	Chiba	Japan	2710077
634	Local Institution	Kasuga	Fukuoka	Japan	816-0864
635	Local Institution	Kurume	Fukuoka	Japan	830-8577
636	Local Institution	Gifu-Shi	Gifu	Japan	5008513
637	Local Institution	Ogaki-Shi	Gifu	Japan	503-8502
638	Local Institution	Kure	Hiroshima	Japan	737-0023
639	Local Institution	Obihiro	Hokkaido	Japan	0808518
640	Local Institution	Sapporo	Hokkaido	Japan	0630005
641	Local Institution	Kasama	Ibaraki	Japan	309-1793
642	Local Institution	Tsuchiura-Shi	Ibaraki	Japan	300-0053
643	Local Institution	Tsukuba	Ibaraki	Japan	3058558
644	Local Institution	Kanazawa	Ishikawa	Japan	9200007
645	Local Institution	Kanoya	Kagoshima	Japan	8930015
646	Local Institution	Yokohama Sakae-Ku	Kanagawa	Japan	247-8581
647	Local Institution	Yokohama	Kanagawa	Japan	232-0024
648	Local Institution	Yokohama	Kanagawa	Japan	234-8503
649	Local Institution	Yokosuka	Kanagawa	Japan	2388567
650	Local Institution	Ueda	Nagano	Japan	386-8610
651	Local Institution	Beppu	Oita	Japan	874-0011
652	Local Institution	Sakai	Osaka	Japan	591-8025
653	Local Institution	Ureshino	Saga	Japan	8430393
654	Local Institution	Ageo	Saitama	Japan	362-8588
655	Local Institution	Koshigaya	Saitama	Japan	3438555
656	Local Institution	Toda	Saitama	Japan	3350023
657	Local Institution	Komatsushima	Tokushima	Japan	7738502
658	Local Institution	Chiyoda-Ku	Tokyo	Japan	101-8643
659	Local Institution	Chuo-Ku	Tokyo	Japan	1048560
660	Local Institution	Hachioji	Tokyo	Japan	1930998
661	Local Institution	Meguro-Ku	Tokyo	Japan	1528902
662	Local Institution	Meguro	Tokyo	Japan	153-8515
663	Local Institution	Iwakuni	Yamaguchi	Japan	7408510
664	Local Institution	Ube	Yamaguchi	Japan	7558505
665	Local Institution	Fukuoka		Japan	814-0180
666	Local Institution	Gifu		Japan	5008727
667	Local Institution	Kochi		Japan	7808522
668	Local Institution	Kumamoto		Japan	8600008
669	Local Institution	Kumamoto		Japan	8608556
670	Local Institution	Kumamoto		Japan	861-4193
671	Local Institution	Kumamoto		Japan	862-0965
672	Local Institution	Kyoto		Japan	6158087
673	Local Institution	Oita		Japan	870-0263
674	Local Institution	Osaka		Japan	558-8558
675	Local Institution	Saga		Japan	840-8571
676	Local Institution	Tokyo		Japan	1600023
677	Local Institution	Wonju	Gangwon-Do	Korea, Republic of	220-701
678	Local Institution	Yangsan	Gyeongangnam-Do	Korea, Republic of	626-770
679	Local Institution	Anyang	Gyeonggi-Do	Korea, Republic of	431-070
680	Local Institution	Guri-Si	Gyeonggi-Do	Korea, Republic of	471-701
681	Local Institution	Jinju	Gyeongsangam-Do	Korea, Republic of	660-702
682	Local Institution	Daegu		Korea, Republic of	705718
683	Local Institution	Goyang		Korea, Republic of	410-773
684	Local Institution	Gwangju		Korea, Republic of	501-757
685	Local Institution	Incheon		Korea, Republic of	400-711
686	Local Institution	Incheon		Korea, Republic of	405-760
687	Local Institution	Jeonbuk		Korea, Republic of	561-712
688	Local Institution	Pusan		Korea, Republic of	602-739
689	Local Institution	Seoul		Korea, Republic of	137-701
690	Local Institution	Seoul		Korea, Republic of	138-736
691	Local Institution	Seoul		Korea, Republic of	152-703
692	Local Institution	Suwon		Korea, Republic of	443-721
693	Local Institution	Cabo San Lucas	Baja Californa Sur	Mexico	23410
694	Local Institution	Tijuana	Baja California	Mexico	22500
695	Local Institution	Monclova	Coahuila	Mexico	25750
696	Local Institution	Metepec	Estado De Mexico	Mexico	52140
697	Local Institution	Tlalnepantla	Estado De Mexico	Mexico	54030
698	Local Institution	Acapulco	Guerrero	Mexico	39570
699	Local Institution	Acapulco	Guerrero	Mexico	39670
700	Local Institution	Pachuca	Hidalgo	Mexico	42070
701	Local Institution	Guadalajara	Jalisco	Mexico	44200
702	Local Institution	Guadalajara	Jalisco	Mexico	44210
703	Local Institution	Guadalajara	Jalisco	Mexico	44280
704	Local Institution	Zapopan	Jalisco	Mexico	45040
705	Local Institution	Monterrey	Nuevo Leon	Mexico	64000
706	Local Institution	Monterrey	Nuevo Leon	Mexico	64060
707	Local Institution	Monterrey	Nuevo Leon	Mexico	64460
708	Local Institution	Monterrey	Nuevo Leon	Mexico	64550
709	Local Institution	Monterrey	Nuevo Leon	Mexico	64710
710	Local Institution	Culiacan	Sinaloa	Mexico	80020
711	Local Institution	Xalapa	Veracruz	Mexico	91190
712	Local Institution	Aguascalientes		Mexico	20127
713	Local Institution	Aguascalientes		Mexico	20230
714	Local Institution	Chihuahua		Mexico	31203
715	Local Institution	Durango		Mexico	34270
716	Local Institution	Queretaro		Mexico	76000
717	Local Institution	San Luis Potosi		Mexico	78240
718	Local Institution	Veracruz		Mexico	91700
719	Local Institution	Alkmaar		Netherlands	1815 JD
720	Local Institution	Almere		Netherlands	1315 RA
721	Local Institution	Amsterdam		Netherlands	1091 AC
722	Local Institution	Beverwijk		Netherlands	1942 LE
723	Local Institution	Boxmeer		Netherlands	5831 HA
724	Local Institution	Den Haag		Netherlands	2597 AX
725	Local Institution	Dirksland		Netherlands	3247 BW
726	Local Institution	Ede		Netherlands	6916 RP
727	Local Institution	Goes		Netherlands	4462 RA
728	Local Institution	Gouda		Netherlands	2803 HH
729	Local Institution	Heerlen		Netherlands	6419 PC
730	Local Institution	Hilversum		Netherlands	1213 XZ
731	Local Institution	Maastrict		Netherlands	6229 HX
732	Local Institution	Meppel		Netherlands	7943KA
733	Local Institution	Purmerend		Netherlands	1441 RN
734	Local Institution	Sneek		Netherlands	8601 ZK
735	Local Institution	Veldhoven		Netherlands	5504 DB
736	Local Institution	Weert		Netherlands	6001 BE
737	Local Institution	Zwolle		Netherlands	8011JW
738	Local Institution	Auckland		New Zealand	1030
739	Local Institution	Auckland		New Zealand	1640
740	Local Institution	Christchurch		New Zealand	8011
741	Local Institution	Hastings		New Zealand	4120
742	Local Institution	Nelson		New Zealand	7010
743	Local Institution	Palmerston North		New Zealand	4410
744	Local Institution	Bergen		Norway	5021
745	Local Institution	Bodo		Norway	8092
746	Local Institution	Drammen		Norway	3004
747	Local Institution	Hamar		Norway	2318
748	Local Institution	Kongsvinger		Norway	2212
749	Local Institution	Kristiansund		Norway	6508
750	Local Institution	Lillehammer		Norway	2629
751	Local Institution	Oslo		Norway	0319
752	Local Institution	Oslo		Norway	0407
753	Local Institution	Oslo		Norway	0514
754	Local Institution	Stavanger		Norway	4011
755	Local Institution	Tynset		Norway	2500
756	Local Institution	Bellavista	Callao	Peru	CALLAO 2
757	Local Institution	Chiclayo	Lambayeque	Peru
758	Local Institution	Callao		Peru	CALLAO 2
759	Local Institution	Cusco		Peru
760	Local Institution	Ica		Peru
761	Local Institution	Lima		Peru	LIMA 11
762	Local Institution	Lima		Peru	LIMA 13
763	Local Institution	Lima		Peru	LIMA 18
764	Local Institution	Lima		Peru	LIMA 1
765	Local Institution	Lima		Peru	LIMA 27
766	Local Institution	Lima		Peru	LIMA 31
767	Local Institution	Lima		Peru	LIMA 33
768	Local Institution	Lima		Peru	LIMA 39
769	Local Institution	Lima		Peru	LIMA 41
770	Local Institution	Wegrow	Mazowiekie	Poland	07-100
771	Local Institution	Bialystok		Poland	15-276
772	Local Institution	Bydgoszcz		Poland	85-826
773	Local Institution	Bytom		Poland	41-902
774	Local Institution	Czestochowa		Poland	42-200
775	Local Institution	Elblag		Poland	82-300
776	Local Institution	Gdynia		Poland	81-423
777	Local Institution	Grodzisk Mazowiecki		Poland	05-825
778	Local Institution	Inowroclaw		Poland	88-100
779	Local Institution	Kielce		Poland	25-736
780	Local Institution	Koscierzyna		Poland	83-400
781	Local Institution	Krakow		Poland	31-202
782	Local Institution	Krakow		Poland	31-501
783	Local Institution	Lodz		Poland	91-347
784	Local Institution	Lodz		Poland	91-425
785	Local Institution	Lublin		Poland	20-089
786	Local Institution	Lublin		Poland	20-954
787	Local Institution	Opole		Poland	45-418
788	Local Institution	Ostrowiec Swietokrzyski		Poland	27-400
789	Local Institution	Plock		Poland	09-402
790	Local Institution	Poznan		Poland	60-479
791	Local Institution	Radom		Poland	26617
792	Local Institution	Rzeszow		Poland	35-301
793	Local Institution	Slupsk		Poland	76-200
794	Local Institution	Szczecin		Poland	70-111
795	Local Institution	Tarnow		Poland	33-100
796	Local Institution	Torun		Poland	87-100
797	Local Institution	Warsaw		Poland	02-507
798	Local Institution	Warszawa		Poland	01-809
799	Local Institution	Warszawa		Poland	04-628
800	Local Institution	Warszawa		Poland	04-749
801	Local Institution	Wloclawek		Poland	87-800
802	Local Institution	Zabrze		Poland	41-800
803	Local Institution	Zielona Gora		Poland	65-046
804	Local Institution	Cidra		Puerto Rico	00739
805	Local Institution	San Juan		Puerto Rico	00917
806	Local Institution	Arad		Romania	310158
807	Local Institution	Baia Mare		Romania	430031
808	Local Institution	Braila		Romania	810249
809	Local Institution	Bucharest		Romania	011461
810	Local Institution	Bucharest		Romania	021659
811	Local Institution	Bucharest		Romania	042122
812	Local Institution	Bucharest		Romania	050098
813	Local Institution	Craiova		Romania	200642
814	Local Institution	Oradea		Romania	410169
815	Local Institution	Pitesti		Romania	110884
816	Local Institution	Sibiu		Romania	550245
817	Local Institution	Targu Mures		Romania	540136
818	Local Institution	Timisoara		Romania	300736
819	Local Institution	Barnaul		Russian Federation	656055
820	Local Institution	Chelyabinsk		Russian Federation	454136
821	Local Institution	Ekaterinburg		Russian Federation	620109
822	Local Institution	Ekaterinburg		Russian Federation	620144
823	Local Institution	Kaluga		Russian Federation	248007
824	Local Institution	Kazan		Russian Federation	420029
825	Local Institution	Kemerovo		Russian Federation	650002
826	Local Institution	Krasnoyarsk		Russian Federation	660058
827	Local Institution	Krasnoyarsk		Russian Federation	660062
828	Local Institution	Moscow Reg. Zhekeznodorozhniy		Russian Federation	143920
829	Local Institution	Moscow		Russian Federation	105229
830	Local Institution	Moscow		Russian Federation	109240
831	Local Institution	Moscow		Russian Federation	111539
832	Local Institution	Moscow		Russian Federation	115093
833	Local Institution	Moscow		Russian Federation	115280
834	Local Institution	Moscow		Russian Federation	117292
835	Local Institution	Moscow		Russian Federation	117593
836	Local Institution	Moscow		Russian Federation	119048
837	Local Institution	Moscow		Russian Federation	119620
838	Local Institution	Moscow		Russian Federation	119991
839	Local Institution	Moscow		Russian Federation	121359
840	Local Institution	Moscow		Russian Federation	121374
841	Local Institution	Moscow		Russian Federation	121552
842	Local Institution	Moscow		Russian Federation	123182
843	Local Institution	Moscow		Russian Federation	125206
844	Local Institution	Moscow		Russian Federation	125284
845	Local Institution	Moscow		Russian Federation	125424
846	Local Institution	Moscow		Russian Federation	127018
847	Local Institution	Moscow		Russian Federation	127473
848	Local Institution	Moscow		Russian Federation	127644
849	Local Institution	Moscow		Russian Federation	129301
850	Local Institution	Moscow		Russian Federation	129327
851	Local Institution	Moscow		Russian Federation	129336
852	Local Institution	Moscow		Russian Federation	19991
853	Local Institution	Nizhni Novgorod		Russian Federation	603003
854	Local Institution	Nizhny Novgorod		Russian Federation	603005
855	Local Institution	Nizhny Novgorod		Russian Federation	603035
856	Local Institution	Novosibirsk		Russian Federation	630003
857	Local Institution	Novosibirsk		Russian Federation	630008
858	Local Institution	Novosibirsk		Russian Federation	630047
859	Local Institution	Novosibirsk		Russian Federation	630089
860	Local Institution	Odintsovo		Russian Federation	143000
861	Local Institution	Penza		Russian Federation	440026
862	Local Institution	Perm		Russian Federation	614036
863	Local Institution	Rostov-On-Don		Russian Federation	344011
864	Local Institution	Ryazan		Russian Federation	390026
865	Local Institution	Saint Petersburg		Russian Federation	191104
866	Local Institution	Saint Petersburg		Russian Federation	193144
867	Local Institution	Saint Petersburg		Russian Federation	193312
868	Local Institution	Saint Petersburg		Russian Federation	196601
869	Local Institution	Saint Petersburg		Russian Federation	197110
870	Local Institution	Saint-Petersburg		Russian Federation	192242
871	Local Institution	Saint-Petersburg		Russian Federation	194156
872	Local Institution	Saint-Petersburg		Russian Federation	195067
873	Local Institution	Saint-Petersburg		Russian Federation	198013
874	Local Institution	Saint-Petersburg		Russian Federation	198205
875	Local Institution	Saratov		Russian Federation	410028
876	Local Institution	Saratov		Russian Federation	410054
877	Local Institution	St. Petersburg		Russian Federation	190000
878	Local Institution	St. Petersburg		Russian Federation	193079
879	Local Institution	St. Petersburg		Russian Federation	194291
880	Local Institution	Tomsk		Russian Federation	634012
881	Local Institution	Tver		Russian Federation	170036
882	Local Institution	Tyumen		Russian Federation	625023
883	Local Institution	Vasilievsky Island		Russian Federation	199106
884	Local Institution	Voronezh		Russian Federation	394065
885	Local Institution	Yaroslavl		Russian Federation	150002
886	Local Institution	Yaroslavl		Russian Federation	150003
887	Local Institution	Yaroslavl		Russian Federation	150030
888	Local Institution	Yaroslavl		Russian Federation	150062
889	Local Institution	Zhukovskiy		Russian Federation	140180
890	Local Institution	Singapore		Singapore	168752
891	Local Institution	Singapore		Singapore	768828
892	Local Institution	Banska Bystrica		Slovakia	97405
893	Local Institution	Bratislava		Slovakia	833 48
894	Local Institution	Kosice		Slovakia	040 01
895	Local Institution	Kosice		Slovakia	040 11
896	Local Institution	Kosice		Slovakia	04001
897	Local Institution	Kralovsky Chlmec		Slovakia	07701
898	Local Institution	Liptovsky Hradok		Slovakia	033 80
899	Local Institution	Lucenec		Slovakia	984 01
900	Local Institution	Martin		Slovakia	03639
901	Local Institution	Nitra		Slovakia	949 01
902	Local Institution	Port Elizabeth	Eastern Cape	South Africa	6001
903	Local Institution	Port Elizabeth	Eastern Cape	South Africa	6045
904	Local Institution	Bloemfontein	Free State	South Africa	9300
905	Local Institution	Bloemfontein	Free State	South Africa	9301
906	Local Institution	Centurion	Gauteng	South Africa	0157
907	Local Institution	Wapadrand - Pretoria	Gauteng	South Africa	0049
908	Local Institution	Durban	Kwa Zulu Natal	South Africa	4001
909	Local Institution	Durban	Kwa Zulu Natal	South Africa	4091
910	Local Institution	Durban	Kwa Zulu Natal	South Africa	4092
911	Local Institution	Umhlanga	Kwa Zulu Natal	South Africa	4321
912	Local Institution	Bellville	Western Cape	South Africa	7530
913	Local Institution	Kuils River	Western Cape	South Africa	7580
914	Local Institution	Pinelands	Western Cape	South Africa	7405
915	Local Institution	Somerset West	Western Cape	South Africa	7130
916	Local Institution	Worcester	Western Cape	South Africa	6850
917	Local Institution	Johannesburg		South Africa	2013
918	Local Institution	Villajoyosa	Alicante	Spain	03570
919	Local Institution	Oviedo	Asturas	Spain	33006
920	Local Institution	Figueres	Gerona	Spain	17600
921	Local Institution	San Sebastian De Los Reyes	Madrid	Spain	28702
922	Local Institution	Almeria		Spain	04120
923	Local Institution	Barcelona		Spain	08003
924	Local Institution	Barcelona		Spain	08035
925	Local Institution	Caceres		Spain	10003
926	Local Institution	El Ejido		Spain	04700
927	Local Institution	Granada		Spain	18014
928	Local Institution	Lleida		Spain	25198
929	Local Institution	Lugo		Spain	27004
930	Local Institution	Madrid		Spain	28006
931	Local Institution	Madrid		Spain	28007
932	Local Institution	Madrid		Spain	28031
933	Local Institution	Madrid		Spain	28041
934	Local Institution	Madrid		Spain	28046
935	Local Institution	Madrid		Spain	28050
936	Local Institution	Malaga		Spain	29010
937	Local Institution	Santiago De Compostela		Spain	15706
938	Local Institution	Sevilla		Spain	41071
939	Local Institution	Tarragona		Spain	43007
940	Local Institution	Torrevieja		Spain	03186
941	Local Institution	Valencia		Spain	46014
942	Local Institution	Valladolid		Spain	47012
943	Local Institution	Zaragoza		Spain	50009
944	Local Institution	Eskilstuna		Sweden	631 88
945	Local Institution	Halmstad		Sweden	30185
946	Local Institution	Helsingborg		Sweden	251 87
947	Local Institution	Karlskoga		Sweden	691 81
948	Local Institution	Karlstad		Sweden	651 85
949	Local Institution	Koping		Sweden	731 81
950	Local Institution	Lidkoping		Sweden	531 85
951	Local Institution	Molndal		Sweden	43180
952	Local Institution	Skovde		Sweden	541 85
953	Local Institution	Stockholm		Sweden	141 86
954	Local Institution	Stockholm		Sweden	171 76
955	Local Institution	Uppsala		Sweden	751 85
956	Local Institution	Vaxjo		Sweden	351 85
957	Local Institution	Lugano	Ticino	Switzerland	6900
958	Local Institution	Geneve		Switzerland	1211
959	Local Institution	St Gallen		Switzerland	9007
960	Local Institution	Zurich		Switzerland	8063
961	Local Institution	Zurich		Switzerland	8091
962	Local Institution	Besevler	Ankara	Turkey	06500
963	Local Institution	Isanbul	Haseki	Turkey
964	Local Institution	Bornova	Izmir	Turkey	35100
965	Local Institution	Ankara		Turkey	06100
966	Local Institution	Diyarbakir		Turkey	21280
967	Local Institution	Isparta		Turkey	32100
968	Local Institution	Kirikkale		Turkey
969	Local Institution	Konya		Turkey	42080
970	Local Institution	Chernivtsy		Ukraine	58013
971	Local Institution	Dnipropetrovsk		Ukraine	49006
972	Local Institution	Dnipropetrovsk		Ukraine	49060
973	Local Institution	Donetsk		Ukraine	83003
974	Local Institution	Donetsk		Ukraine	83045
975	Local Institution	Donetsk		Ukraine	83114
976	Local Institution	Ivano-Frankivsk		Ukraine	76025
977	Local Institution	Kharkiv		Ukraine	61002
978	Local Institution	Kharkiv		Ukraine	61018
979	Local Institution	Kharkiv		Ukraine	61039
980	Local Institution	Kharkiv		Ukraine	61115
981	Local Institution	Kharkiv		Ukraine	61176
982	Local Institution	Kyiv		Ukraine	02091
983	Local Institution	Kyiv		Ukraine	02660
984	Local Institution	Kyiv		Ukraine	03115
985	Local Institution	Kyiv		Ukraine	03151
986	Local Institution	Lugansk		Ukraine	91016
987	Local Institution	Lutsk		Ukraine	43024
988	Local Institution	Lviv		Ukraine	79010
989	Local Institution	Lviv		Ukraine	79015
990	Local Institution	Mykolayiv		Ukraine	54003
991	Local Institution	Odessa		Ukraine	65014
992	Local Institution	Odessa		Ukraine	65059
993	Local Institution	Simferopol		Ukraine	95026
994	Local Institution	Vinnitsa		Ukraine	21029
995	Local Institution	Zhaporizhzhya		Ukraine	69000
996	Local Institution	Belfast	Antrim	United Kingdom	BT9 7AB
997	Local Institution	Belfast	Armagh	United Kingdom	BT12 6BA
998	Local Institution	Portadown	Armagh	United Kingdom	BT63 5QQ
999	Local Institution	Ayr	Ayrshire	United Kingdom	KA6 6DX
1000	Local Institution	Kilmarnock	Ayrshire	United Kingdom	KA2 0BE
1001	Local Institution	Cambridge	Cambridgeshire	United Kingdom	CB2 0QQ
1002	Local Institution	Chesterfield	Derbyshire	United Kingdom	S445BL
1003	Local Institution	Dumfries	Dumfriesshire	United Kingdom	DG1 4AP
1004	Local Institution	Cottingham	East Yorkshire	United Kingdom	HU16 5JQ
1005	Local Institution	Basildon	Essex	United Kingdom	SS16 5NL
1006	Local Institution	Chelmsford	Essex	United Kingdom	CM1 7ET
1007	Local Institution	Romford	Essex	United Kingdom	RM7 0AG
1008	Local Institution	Tunbridge Wells	Kent	United Kingdom	TN4 8AT
1009	Local Institution	Blackpool	Lancashire	United Kingdom	FY3 8NR
1010	Local Institution	Scunthorpe	Lincolnshire	United Kingdom	DN15 7BH
1011	Local Institution	Harrow	Middlesex	United Kingdom	HA1 3UJ
1012	Local Institution	Worksop	Nottinghamshire	United Kingdom	S18 0BD
1013	Local Institution	Doncaster	South Yorkshire	United Kingdom	DN2 5LT
1014	Local Institution	New Castle Upon Tyne	Tyne And Wear	United Kingdom	NE7 7DN

Sponsors and Collaborators

• Bristol-Myers Squibb
• Pfizer
• Duke Clinical Research Institute

Investigators

• Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT00831441
• Other Study ID Numbers: CV185-068; EUDRACT# 2008-008298-77
• First Posted: Jan 29, 2009
• Last Update Posted: Jan 27, 2016
• Last Verified: Dec 1, 2015

• Keywords provided by Bristol-Myers Squibb: NOS
• Additional relevant MeSH terms: Acute Coronary Syndrome; Syndrome; Apixaban

Study Results

Participant Flow

Pre-assignment Detail	7484 participants enrolled and 7392 were randomized. Reasons for non-randomization: 2 Adverse event (AE), 18 withdrew consent, 1 lost to follow up, 3 administrative reason by sponsor, 2 deaths, 51 no longer met criteria, 15 other.

Arm/Group Title	Placebo BID	Apixaban 5 mg BID
Arm/Group Description	Placebo: Tablets, Oral, 0 mg, twice daily. The Treatment Period was planned to be completed after at least 938 participants had a primary efficacy endpoint confirmed by adjudication. After 7392 participants had been randomized into the study, an independent Data Monitoring Committee recommended that the study be terminated early due to a clinically important increase in bleeding among participants randomized to apixaban which was not offset by meaningful reductions in ischemic events. The Study terminated in Year 2.	Apixaban: Tablets, Oral, 5 mg, twice daily. The Treatment Period was planned to be completed after at least 938 participants had a primary efficacy endpoint confirmed by adjudication. After 7392 participants had been randomized into the study, an independent Data Monitoring Committee recommended that the study be terminated early due to a clinically important increase in bleeding among participants randomized to apixaban which was not offset by meaningful reductions in ischemic events. The Study terminated in Year 2.
Period Title: Randomized
STARTED	3687	3705
Treated	3643	3672
COMPLETED	0	0
NOT COMPLETED	3687	3705
Period Title: Randomized
STARTED	3508	3529
COMPLETED	3375	3355
NOT COMPLETED	133	174

Baseline Characteristics

Arm/Group Title	Placebo	Apixaban 5 mg BID	Total
Arm/Group Description	Placebo: Tablets, Oral, 0 mg, twice daily.	Apixaban: Tablets, Oral, 5 mg, twice daily.	Total of all reporting groups
Overall Participants	3687	3705	7392
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	65.4 (11.05)	65.3 (10.89)	65.4 (10.97)
Age, Customized (participants) [Number]
< 65 years	1512 41%	1526 41.2%	3038 41.1%
≥ 65 and < 75 years	1420 38.5%	1440 38.9%	2860 38.7%
≥ 75 years	755 20.5%	739 19.9%	1494 20.2%
Sex: Female, Male (Count of Participants)
Female	1169 31.7%	1209 32.6%	2378 32.2%
Male	2518 68.3%	2496 67.4%	5014 67.8%
Region of Enrollment (participants) [Number]
Russian Federation	540 14.6%	542 14.6%	1082 14.6%
Puerto Rico	13 0.4%	17 0.5%	30 0.4%
Singapore	11 0.3%	14 0.4%	25 0.3%
United States	450 12.2%	455 12.3%	905 12.2%
Austria	58 1.6%	56 1.5%	114 1.5%
Sweden	50 1.4%	55 1.5%	105 1.4%
Netherlands	45 1.2%	52 1.4%	97 1.3%
China	36 1%	39 1.1%	75 1%
Poland	176 4.8%	177 4.8%	353 4.8%
Korea, Republic of	88 2.4%	89 2.4%	177 2.4%
Brazil	125 3.4%	125 3.4%	250 3.4%
Slovakia	30 0.8%	29 0.8%	59 0.8%
France	22 0.6%	18 0.5%	40 0.5%
Bulgaria	100 2.7%	102 2.8%	202 2.7%
Chile	30 0.8%	26 0.7%	56 0.8%
Colombia	45 1.2%	43 1.2%	88 1.2%
Argentina	131 3.6%	125 3.4%	256 3.5%
Romania	78 2.1%	80 2.2%	158 2.1%
Hungary	121 3.3%	120 3.2%	241 3.3%
Japan	91 2.5%	95 2.6%	186 2.5%
Ukraine	128 3.5%	130 3.5%	258 3.5%
United Kingdom	24 0.7%	21 0.6%	45 0.6%
Switzerland	18 0.5%	20 0.5%	38 0.5%
India	396 10.7%	398 10.7%	794 10.7%
Spain	81 2.2%	79 2.1%	160 2.2%
New Zealand	13 0.4%	9 0.2%	22 0.3%
Canada	126 3.4%	128 3.5%	254 3.4%
Czech Republic	54 1.5%	54 1.5%	108 1.5%
Turkey	9 0.2%	11 0.3%	20 0.3%
Belgium	47 1.3%	50 1.3%	97 1.3%
Norway	26 0.7%	25 0.7%	51 0.7%
Finland	4 0.1%	3 0.1%	7 0.1%
Denmark	37 1%	34 0.9%	71 1%
Italy	23 0.6%	21 0.6%	44 0.6%
South Africa	66 1.8%	67 1.8%	133 1.8%
Mexico	161 4.4%	161 4.3%	322 4.4%
Israel	73 2%	66 1.8%	139 1.9%
Australia	15 0.4%	23 0.6%	38 0.5%
Peru	66 1.8%	66 1.8%	132 1.8%
Germany	80 2.2%	80 2.2%	160 2.2%
Antiplatelet Therapy (participants) [Number]
Dual Antiplatelet Therapy	2965 80.4%	2968 80.1%	5933 80.3%
Single Antiplatelet Therapy	722 19.6%	737 19.9%	1459 19.7%
ACS Index Event (participants) [Number]
STEMI	1412 38.3%	1426 38.5%	2838 38.4%
non-STEMI	1582 42.9%	1581 42.7%	3163 42.8%
Unstable angina	693 18.8%	698 18.8%	1391 18.8%

Outcome Measures

1. Primary Outcome

Title	Event Rate of Cardiovascular Death, Myocardial Infarction, or Ischemic Stroke During the Intended Treatment Period - Randomized Participants
Description	Event rate was percent of participants with an event of cardiovascular (CV) death, myocardial infarction (MI), or ischemic stroke (number of participants with event/number randomized) per 100 patient (100-pt) years. Study was terminated early and last patient, last visit was in Year 2. Only events confirmed by the adjudication committee were included in the analyses. CV death included deaths due to CV causes (eg, cardiogenic shock, heart failure, arrhythmia/sudden death, cardiac rupture, ischemic stroke, pulmonary embolism, venous/arterial thrombotic events) and other sudden deaths for which an alternative cause was not identified. Intended Treatment Period: the period that started on the day of randomization and ended at the efficacy cut-off date (cut-off date: the date all sites were informed that study drug should be discontinued for all participants, 18 November 2010).
Time Frame	Randomization (Day 1) to first event (CV death, MI, ischemic stroke), up to March 2011, approximately 2 years

Outcome Measure Data

Analysis Population Description

All randomized participants were analyzed.

Arm/Group Title	Placebo	Apixaban 5 mg BID
Arm/Group Description	Placebo: Tablets, Oral, 0 mg, twice daily.	Apixaban: Tablets, Oral, 5 mg, twice daily. Study was terminated in Year 2.
Measure Participants	3687	3705
Number [percentage of participants/100-pt years]	13.96 0.4%	13.20 0.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apixaban 5 mg BID
	Comments	A test of superiority at the one-sided α = 0.025 significance level for the primary efficacy outcome was performed.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5094
	Comments
	Method	Cox proportional hazard models
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.95
	Confidence Interval	(2-Sided) 95%; 0.80 to 1.11
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Event Rate of Unstable Angina (UA) During the Intended Treatment Period - Randomized Participants
Description	Unstable Angina (UA) defined as worsening or recurrent severe or repetitive angina symptoms at rest lasting at least 10 minutes with at least 2 of the following: New and dynamic electrocardiogram (ECG) changes; angina symptoms leading to inpatient hospitalization; angina symptoms leading to an unplanned or urgent cardiac catheterization, with or without revascularization, that showed evidence of hemodynamically and clinically significant stenosis. Event rate was percent of participants with an event of unstable angina (number of participants with event/number randomized) per 100 patient (100-pt) years. Only events confirmed by the adjudication committee were included in the analyses. Intended Treatment Period: the period that started on the day of randomization and ended at the efficacy cut-off date (cut-off date: the date all sites were informed that study drug should be discontinued for all participants, 18 November 2010).
Time Frame	Randomization (Day 1) to first event of UA, up to March 2011, approximately 2 years

Outcome Measure Data

Analysis Population Description

All randomized participants were analyzed.

Arm/Group Title	Placebo	Apixaban 5 mg BID
Arm/Group Description	Placebo: Tablets, Oral, 0 mg, twice daily.	Apixaban: Tablets, Oral, 5 mg, twice daily. Study was terminated at Year 2.
Measure Participants	3687	3705
Number [percentage of participants/100-pt years]	4.21 0.1%	3.95 0.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apixaban 5 mg BID
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6702
	Comments
	Method	Cox proportional hazard models
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.94
	Confidence Interval	(2-Sided) 95%; 0.70 to 1.26
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Event Rate of Stroke During the Intended Treatment Period - Randomized Participants
Description	Event rate was percent of participants with an event of stroke (number of participants with event/number randomized) per 100 patient (100-pt) years. Only events confirmed by the adjudication committee were included in the analyses. Diagnosis of stroke required a new, non-traumatic, focal neurological deficit of sudden onset, lasting at least 24 hours that was not due to a readily identifiable non-vascular cause (ie, brain tumor). All strokes were classified as hemorrhagic (documentation on imaging (eg computed tomography scan or magnetic resonance imaging) of hemorrhage in the cerebral parenchyma, or a subdural or subarachnoid hemorrhage), non-hemorrhagic/ischemic stroke, ischemic stroke with hemorrhagic conversion, or type unknown. Intended Treatment Period: the period that started on the day of randomization (Day 1) and ended at the efficacy cut-off date (notification of study termination).
Time Frame	Randomization (Day 1) to first event (stroke), up to March 2011, approximately 2 years

Outcome Measure Data

Analysis Population Description

All randomized participants were analyzed.

Arm/Group Title	Placebo	Apixaban 5 mg BID
Arm/Group Description	Placebo: Tablets, Oral, 0 mg, twice daily.	Apixaban: Tablets, Oral, 5 mg, twice daily. Study was terminated at Year 2.
Measure Participants	3687	3705
Number [percentage of participants/100-pt years]	1.85 0.1%	1.65 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apixaban 5 mg BID
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6311
	Comments
	Method	Cox proportional hazard models
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.90
	Confidence Interval	(2-Sided) 95%; 0.57 to 1.40
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Event Rate of Myocardial Infarction (MI) During the Intended Treatment Period - Randomized Participants
Description	MI took into account whether the participant had a recent percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery. Selected key criteria: Elevation of cardiac biomarkers (eg, Creatine Kinase MB fraction (CKMB), Troponin T, Troponin I) above the upper reference limit (URL) plus ischemic symptoms, ECG changes, or imaging evidence of new loss of viable myocardium or new regional wall motion abnormality; Death of CV etiology with new ST-segment elevation or left bundle branch block (LBBB) or fresh intracoronary thrombus by angiography or at autopsy occurring before biomarkers could be obtained or before their appearance in the blood; Following a PCI, elevation of cardiac biomarkers more than 3*URL; Following CABG surgery, elevation of cardiac biomarkers more than 5*URL; New, significant (≥0.04 s) Q waves in ≥2 contiguous leads; Pathologic findings of acute MI. Intended Treatment Period: Day of randomization (Day 1) to efficacy cut-off notice.
Time Frame	Randomization (Day 1) to first event (MI), up to March 2011, approximately 2 years

Outcome Measure Data

Analysis Population Description

All randomized participants were analyzed.

Arm/Group Title	Placebo	Apixaban 5 mg BID
Arm/Group Description	Placebo: Tablets, Oral, 0 mg, twice daily.	Apixaban: Tablets, Oral, 5 mg, twice daily. Study was terminated at Year 2.
Measure Participants	3687	3705
Number [percentage of participants/100-pt years]	9.20 0.2%	8.59 0.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apixaban 5 mg BID
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5086
	Comments
	Method	Cox proportional hazard models
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.93
	Confidence Interval	(2-Sided) 95%; 0.76 to 1.14
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Event Rate of Stent Thrombosis During the Intended Treatment Period - Randomized Participants
Description	Stent thrombosis: Definite stent thrombosis considered to have occurred by either angiographic or pathological confirmation; Probable stent thrombosis considered to have occurred in the following cases: any unexplained death within the first 30 days after stent implantation; irrespective of the time after the procedure, any MI that was related to documented acute ischemia in the territory of the implanted stent without angiographic confirmation of stent thrombosis and in the absence of any other obvious cause; Possible stent thrombosis considered to have occurred with any unexplained death from 30 days after intracoronary stenting until end of study (in Year 2). Event rate was percent of participants with an event of stent thrombosis (number with event/number randomized) per 100-pt years. Only events confirmed by the adjudication committee were included in the analyses. Intended Treatment Period: Day of randomization (Day 1) to efficacy cut-off notice of study termination.
Time Frame	Randomization (Day 1) to first event (stent thrombosis), up to March 2011, approximately 2 years

Outcome Measure Data

Analysis Population Description

All randomized participants were analyzed.

Arm/Group Title	Placebo	Apixaban 5 mg BID
Arm/Group Description	Placebo: Tablets, Oral, 0 mg, twice daily.	Apixaban: Tablets, Oral, 5 mg, twice daily. Study was terminated at Year 2.
Measure Participants	3687	3705
Number [percentage of participants/100-pt years]	2.21 0.1%	1.61 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apixaban 5 mg BID
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1502
	Comments
	Method	Cox proportional hazard models
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.73
	Confidence Interval	(2-Sided) 95%; 0.47 to 1.12
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Event Rate of Composite of Cardiovascular Death, Myocardial Infarction, Unstable Angina, or Ischemic Stroke During the Intended Treatment Period - Randomized Participants
Description	Event rate was percent of participants with an event of CV death, MI, unstable angina (UA), or ischemic stroke (number of participants with event/number randomized) per 100-pt years. Only events confirmed by the adjudication committee were included in the analyses. Each type of event was counted once per participant, but participants could have been counted in multiple categories. Intended Treatment Period: Day of randomization (Day 1) to efficacy cut-off date (notification of study termination).
Time Frame	Randomization (Day 1) to first event (CV death, MI, UA, Ischemic Stroke, up to March 2011, approximately 2 years

Outcome Measure Data

Analysis Population Description

All randomized participants were analyzed.

Arm/Group Title	Placebo	Apixaban 5 mg BID
Arm/Group Description	Placebo: Tablets, Oral, 0 mg, twice daily.	Apixaban: Tablets, Oral, 5 mg, twice daily. Study was terminated at Year 2.
Measure Participants	3687	3705
Number [percentage of participants/100-pt years]	17.95 0.5%	16.92 0.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apixaban 5 mg BID
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4317
	Comments
	Method	Cox proportional hazard models
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.94
	Confidence Interval	(2-Sided) 95%; 0.82 to 1.09
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Event Rate of Composite of Cardiovascular Death, Fatal Bleed, Myocardial Infarction, or Stroke During the Intended Treatment Period - Randomized Participants
Description	Event rate was percent of participants with an event of CV death, fatal bleed, MI, or stroke (number of participants with event/number randomized) per 100 patient (100-pt) years. Only events confirmed by the adjudication committee were included in the analyses. CV death included deaths due to CV causes; Diagnosis of stroke required a new, non-traumatic, focal neurological deficit of sudden onset, lasting at least 24 hours that was not due to a readily identifiable non-vascular cause; Fatal bleeding defined as bleeding that Adjudication Committee determined was the primary cause of death or contributed directly to death; MI took into account whether the participant had a recent PCI or CABG surgery. Intended Treatment Period: Day of randomization (Day 1) to efficacy cut-off date (notification of study termination).
Time Frame	Randomization (Day 1) to first event (CV death, Fatal Bleed, MI, or stroke), up to March 2011, approximately 2 years

Outcome Measure Data

Analysis Population Description

All randomized participants were analyzed.

Arm/Group Title	Placebo	Apixaban 5 mg BID
Arm/Group Description	Placebo: Tablets, Oral, 0 mg, twice daily.	Apixaban: Tablets, Oral, 5 mg, twice daily. Study was terminated at Year 2.
Measure Participants	3687	3705
Number [percentage of participants/100-pt years]	14.27 0.4%	13.97 0.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apixaban 5 mg BID
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8015
	Comments
	Method	Cox proportional hazard models
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.98
	Confidence Interval	(2-Sided) 95%; 0.83 to 1.15
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Event Rate of Composite of All-Cause Death, Myocardial Infarction, or Stroke During the Intended Treatment Period - Randomized Participants
Description	Cause of death was determined by the principal condition that caused the death, not the immediate mode of death. CV death: included deaths due to CV causes. Non-CV death: included non-CV deaths caused primarily by a malignancy, infection, bleeding, trauma, non-CV system organ failure, or non-CV surgery. Unknown: included deaths that were not attributable to one of the above categories of CV death or to a non-CV cause. MI accounted whether the participant had a recent PCI or CABG surgery. Diagnosis of stroke required a new, non-traumatic, focal neurological deficit of sudden onset, lasting at least 24 hours that was not due to a readily identifiable non-vascular cause. Only events confirmed by the adjudication committee were included in analyses. Intended Treatment Period: Day of randomization (Day 1) to efficacy cut-off date (notification of study termination).
Time Frame	Randomization (Day 1) to first event (All Cause Death, MI, or Stroke), up to March 2011, approximately 2 years

Outcome Measure Data

Analysis Population Description

All randomized participants were analyzed.

Arm/Group Title	Placebo	Apixaban 5 mg BID
Arm/Group Description	Placebo: Tablets, Oral, 0 mg, twice daily.	Apixaban: Tablets, Oral, 5 mg, twice daily. Study was terminated at Year 2.
Measure Participants	3687	3705
Number [percentage of participants/100-pt years]	15.65 0.4%	15.48 0.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apixaban 5 mg BID
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8948
	Comments
	Method	Cox proportional hazard models
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.99
	Confidence Interval	(2-Sided) 95%; 0.85 to 1.15
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Primary Outcome

Title	Event Rate of Confirmed Major Bleeding Using Thrombolysis in Myocardial Infarction (TIMI) Criteria During the Treatment Period - Treated Participants
Description	TIMI Major Bleed Criteria: Fatal bleeding, intracranial hemorrhage, and clinically overt bleeding with a hemoglobin (Hgb) drop of ≥ 5 grams per deciliter (g/dL), or ≥15% absolute decrease in hematocrit. To account for transfusions, Hgb measurements were adjusted for transfusions. A transfusion of 1 unit of blood was assumed to result in an increase by 1 g/dL in Hgb or 3% in hematocrit. Event rate was percent of participants with an event of Major Bleed as per TIMI (number of participants with event/number randomized) per 100 patient (100-pt) years. Only events confirmed by the adjudication committee were included in the analyses. Treatment Period=events with onset from first dose to last dose plus 2 days.
Time Frame	From first dose to first occurrence of event (TIMI major bleeding) during Treatment Period (first dose to last dose + 2 days), up to March 2011, approximately 2 years

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of blinded study drug and signed informed consent were analyzed.

Arm/Group Title	Placebo	Apixaban 5 mg BID
Arm/Group Description	Placebo: Tablets, Oral, 0 mg, twice daily.	Apixaban: Tablets, Oral, 5 mg, twice daily. Study was terminated at Year 2.
Measure Participants	3643	3672
Number [percentage of participants/100-pt years]	0.91 0%	2.40 0.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apixaban 5 mg BID
	Comments	A point estimate and two-sided 95% confidence interval (CI) for relative risk, as measured by the hazard ratio and a p-value for the test of equality of rates (HR = 1) was calculated.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0006
	Comments
	Method	Cox Proportional Hazard model
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	2.59
	Confidence Interval	(2-Sided) 95%; 1.50 to 4.46
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Event Rate of Confirmed Major Bleeding Using International Society on Thrombosis and Hemostasis (ISTH) Criteria During the Treatment Period - Treated Participants
Description	ISTH Criteria: Acute clinically overt bleeding defined as new onset, visible bleeding or signs or symptoms suggestive of bleeding confirmed by imaging techniques, which can detect the presence of blood (eg, ultrasound, CT, MRI). Major bleeding: acute clinically overt bleeding accompanied by one or more of the following: A decrease in Hgb of 2 g/dL or more over 24 hours; A transfusion of 2 or more units of packed red blood cells (RBCs); Bleeding that occurs in at least one of the following sites: intracranial, intraspinal, intraocular (within the corpus of the eye; thus, a conjunctival bleed is not an intraocular bleed), pericardial, intra-articular, intramuscular with compartment syndrome, retroperitoneal; Bleeding that was fatal. Bleeding events were adjudicated by the Adjudication Committee. Event rate was percent of participants with an event (number with event/number randomized) per 100-pt years. Treatment Period=events with onset from first dose to last dose plus 2 days.
Time Frame	From first dose to first occurrence of event (ISTH major bleed) during Treatment Period (first dose to last dose + 2 days), up to March 2011, approximately 2 years

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of blinded study drug and signed informed consent were analyzed.

Arm/Group Title	Placebo	Apixaban 5 mg BID
Arm/Group Description	Placebo: Tablets, Oral, 0 mg, twice daily.	Apixaban: Tablets, Oral, 5 mg, twice daily. Study was terminated at Year 2.
Measure Participants	3643	3672
Number [percentage of participants/100-pt years]	2.04 0.1%	5.13 0.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apixaban 5 mg BID
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cox Proportional Hazard model
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	2.48
	Confidence Interval	(2-Sided) 95%; 1.72 to 3.58
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	Event Rate of Confirmed Major Bleeding or Clinically Relevant Non-Major Bleeding (CRNM) Using ISTH Criteria During the Treatment Period - Treated Participants
Description	ISTH Major bleed: acute clinically overt bleeding accompanied by one or more of the following: A decrease in Hgb of 2 g/dL or more over 24 hours; A transfusion of 2 or more units of packed RBCs; Bleeding that occurs in at least one of the following critical sites: intracranial, intraspinal, intraocular (within the corpus of the eye), pericardial, intra-articular, intramuscular with compartment syndrome, retroperitoneal; Bleeding that was fatal. CRNM: acute clinically overt bleeding that did not satisfy additional criteria required for the bleeding event to be defined as a major bleeding event and meets at least one of the following: Hospital admission for bleeding; Physician guided medical or surgical treatment for bleeding; Change in anti-thrombotic treatment (anticoagulant or antiplatelet) therapy. Bleeding events were adjudicated by the Adjudication Committee. Treatment Period=events with onset from first dose to last dose plus 2 days.
Time Frame	From first dose to first occurrence of event (ISTH major or CRNM bleed) during Treatment Period (first dose to last dose + 2 days), up to March 2011, approximately 2 years

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of blinded study drug and signed informed consent were analyzed.

Arm/Group Title	Placebo	Apixaban 5 mg BID
Arm/Group Description	Placebo: Tablets, Oral, 0 mg, twice daily.	Apixaban: Tablets, Oral, 5 mg, twice daily. Study was terminated at Year 2.
Measure Participants	3643	3672
Number [percentage of participants/100-pt years]	2.29 0.1%	6.15 0.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apixaban 5 mg BID
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cox Proportional Hazard model
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	2.64
	Confidence Interval	(2-Sided) 95%; 1.87 to 3.72
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

Title	Event Rate of All Bleeding Reported by the Investigator During the Treatment Period - Treated Participants
Description	Bleeding events were adjudicated by the Adjudication Committee and classified according to Thrombolysis in Myocardial Infarction (TIMI) major, minor, minimal, and International Society on Thrombosis and Hemostasis (ISTH) major and clinically relevant non-major bleeding (CRNM) criteria. The adjudicated results based on TIMI and ISTH classifications, and programmatically identified events (not adjudicated) according to Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) classification were used in the analyses of bleeding endpoints. GUSTO Bleed Criteria included Severe or life-threatening: Intracranial hemorrhage, or bleeding that causes hemodynamic compromise requiring intervention; Moderate: Bleeding that requires a blood transfusion, but does not result in hemodynamic compromise; Mild: Bleeding that does not meet criteria for either severe or moderate bleeding. Treatment Period=events with onset from first dose to last dose plus 2 days.
Time Frame	From first dose to first occurrence of event (Bleeding) during Treatment Period (first dose to last dose + 2 days), up to March 2011, approximately 2 years

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of blinded study drug and signed informed consent were analyzed.

Arm/Group Title	Placebo	Apixaban 5 mg BID
Arm/Group Description	Placebo: Tablets, Oral, 0 mg, twice daily.	Apixaban: Tablets, Oral, 5 mg, twice daily. Study was terminated at Year 2.
Measure Participants	3643	3672
Number [percentage of participants/100-pt years]	16.33 0.4%	39.98 1.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apixaban 5 mg BID
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cox Proportional Hazard model
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	2.36
	Confidence Interval	(2-Sided) 95%; 2.06 to 2.70
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Arm/Group Title	Apixaban 5 mg BID		Placebo BID
Arm/Group Description	Apixaban: Tablets, Oral, 5 mg, twice daily. The Treatment Period was planned to be completed after at least 938 participants had a primary efficacy endpoint confirmed by adjudication. After 7392 participants had been randomized into the study, an independent Data Monitoring Committee recommended that the study be terminated early due to a clinically important increase in bleeding among participants randomized to apixaban which was not offset by meaningful reductions in ischemic events. The Study terminated in Year 2.		Placebo: Tablets, Oral, 0 mg, twice daily. The Treatment Period was planned to be completed after at least 938 participants had a primary efficacy endpoint confirmed by adjudication. After 7392 participants had been randomized into the study, an independent Data Monitoring Committee recommended that the study be terminated early due to a clinically important increase in bleeding among participants randomized to apixaban which was not offset by meaningful reductions in ischemic events. The Study terminated in Year 2.
All Cause Mortality
	Apixaban 5 mg BID		Placebo BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Apixaban 5 mg BID		Placebo BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	894/3672 (24.3%)		884/3643 (24.3%)
Blood and lymphatic system disorders
Iron deficiency anaemia	0/3672 (0%)		2/3643 (0.1%)
Thrombocytopenia	1/3672 (0%)		1/3643 (0%)
Eosinophilia	1/3672 (0%)		0/3643 (0%)
Leukocytosis	0/3672 (0%)		1/3643 (0%)
Haemorrhagic anaemia	0/3672 (0%)		1/3643 (0%)
Anaemia	16/3672 (0.4%)		8/3643 (0.2%)
Nephrogenic anaemia	0/3672 (0%)		2/3643 (0.1%)
Lymphadenopathy	1/3672 (0%)		0/3643 (0%)
Cardiac disorders
Arteriospasm coronary	1/3672 (0%)		0/3643 (0%)
Atrial flutter	2/3672 (0.1%)		2/3643 (0.1%)
Cardiac failure acute	6/3672 (0.2%)		3/3643 (0.1%)
Cardiac failure congestive	16/3672 (0.4%)		17/3643 (0.5%)
Cardiomyopathy	2/3672 (0.1%)		1/3643 (0%)
Interventricular septum rupture	1/3672 (0%)		0/3643 (0%)
Supraventricular extrasystoles	1/3672 (0%)		0/3643 (0%)
Angina pectoris	37/3672 (1%)		41/3643 (1.1%)
Atrioventricular block	1/3672 (0%)		1/3643 (0%)
Bundle branch block left	0/3672 (0%)		1/3643 (0%)
Cardiac arrest	4/3672 (0.1%)		4/3643 (0.1%)
Cardiac failure chronic	1/3672 (0%)		3/3643 (0.1%)
Ventricular asystole	0/3672 (0%)		1/3643 (0%)
Ventricular tachycardia	8/3672 (0.2%)		11/3643 (0.3%)
Acute coronary syndrome	1/3672 (0%)		1/3643 (0%)
Cardiopulmonary failure	1/3672 (0%)		0/3643 (0%)
Coronary artery insufficiency	1/3672 (0%)		1/3643 (0%)
Coronary artery occlusion	3/3672 (0.1%)		4/3643 (0.1%)
Coronary artery stenosis	20/3672 (0.5%)		16/3643 (0.4%)
Ischaemic cardiomyopathy	1/3672 (0%)		3/3643 (0.1%)
Left ventricular failure	1/3672 (0%)		3/3643 (0.1%)
Atrioventricular block second degree	0/3672 (0%)		1/3643 (0%)
Cardiac failure	94/3672 (2.6%)		82/3643 (2.3%)
Cardio-respiratory arrest	1/3672 (0%)		3/3643 (0.1%)
Dressler's syndrome	1/3672 (0%)		0/3643 (0%)
Myocardial ischaemia	1/3672 (0%)		4/3643 (0.1%)
Sick sinus syndrome	0/3672 (0%)		3/3643 (0.1%)
Sinus bradycardia	0/3672 (0%)		1/3643 (0%)
Aortic valve incompetence	2/3672 (0.1%)		0/3643 (0%)
Arrhythmia	4/3672 (0.1%)		1/3643 (0%)
Atrioventricular block complete	0/3672 (0%)		5/3643 (0.1%)
Cardiogenic shock	2/3672 (0.1%)		7/3643 (0.2%)
Prinzmetal angina	1/3672 (0%)		0/3643 (0%)
Tachycardia	0/3672 (0%)		1/3643 (0%)
Ventricular fibrillation	8/3672 (0.2%)		5/3643 (0.1%)
Acute left ventricular failure	1/3672 (0%)		1/3643 (0%)
Atrial fibrillation	26/3672 (0.7%)		29/3643 (0.8%)
Cardiac disorder	1/3672 (0%)		0/3643 (0%)
Cardiac perforation	0/3672 (0%)		1/3643 (0%)
Cardiac tamponade	1/3672 (0%)		0/3643 (0%)
Congestive cardiomyopathy	1/3672 (0%)		0/3643 (0%)
Mitral valve incompetence	0/3672 (0%)		1/3643 (0%)
Myocardial infarction	150/3672 (4.1%)		158/3643 (4.3%)
Parasystole	1/3672 (0%)		0/3643 (0%)
Pericarditis	0/3672 (0%)		1/3643 (0%)
Sinus tachycardia	1/3672 (0%)		0/3643 (0%)
Ventricle rupture	1/3672 (0%)		0/3643 (0%)
Angina unstable	157/3672 (4.3%)		157/3643 (4.3%)
Coronary artery dissection	0/3672 (0%)		1/3643 (0%)
Pericardial effusion	4/3672 (0.1%)		0/3643 (0%)
Pericardial haemorrhage	3/3672 (0.1%)		4/3643 (0.1%)
Ventricular arrhythmia	2/3672 (0.1%)		1/3643 (0%)
Arteriosclerosis coronary artery	6/3672 (0.2%)		3/3643 (0.1%)
Bradycardia	9/3672 (0.2%)		3/3643 (0.1%)
Cardiovascular insufficiency	0/3672 (0%)		1/3643 (0%)
Coronary artery disease	22/3672 (0.6%)		18/3643 (0.5%)
Intracardiac thrombus	0/3672 (0%)		2/3643 (0.1%)
Left ventricular dysfunction	2/3672 (0.1%)		1/3643 (0%)
Myocardial rupture	1/3672 (0%)		1/3643 (0%)
Sinus arrhythmia	0/3672 (0%)		1/3643 (0%)
Ventricular extrasystoles	1/3672 (0%)		0/3643 (0%)
Ear and labyrinth disorders
Vertigo	2/3672 (0.1%)		4/3643 (0.1%)
Vertigo positional	1/3672 (0%)		0/3643 (0%)
Endocrine disorders
Hyperthyroidism	2/3672 (0.1%)		0/3643 (0%)
Eye disorders
Cataract	1/3672 (0%)		4/3643 (0.1%)
Eye haemorrhage	2/3672 (0.1%)		0/3643 (0%)
Maculopathy	0/3672 (0%)		1/3643 (0%)
Retinal detachment	1/3672 (0%)		1/3643 (0%)
Gastrointestinal disorders
Oesophageal ulcer	0/3672 (0%)		1/3643 (0%)
Oesophagitis	1/3672 (0%)		0/3643 (0%)
Thrombosis mesenteric vessel	0/3672 (0%)		1/3643 (0%)
Duodenal ulcer	2/3672 (0.1%)		0/3643 (0%)
Impaired gastric emptying	1/3672 (0%)		0/3643 (0%)
Irritable bowel syndrome	0/3672 (0%)		1/3643 (0%)
Pancreatitis acute	1/3672 (0%)		1/3643 (0%)
Pancreatitis chronic	1/3672 (0%)		1/3643 (0%)
Periproctitis	1/3672 (0%)		0/3643 (0%)
Subileus	0/3672 (0%)		1/3643 (0%)
Gastroduodenitis	0/3672 (0%)		1/3643 (0%)
Gastrointestinal haemorrhage	69/3672 (1.9%)		23/3643 (0.6%)
Ischaemic gastritis	0/3672 (0%)		1/3643 (0%)
Pharyngoesophageal diverticulum	1/3672 (0%)		0/3643 (0%)
Ascites	0/3672 (0%)		1/3643 (0%)
Diabetic gastroparesis	1/3672 (0%)		0/3643 (0%)
Duodenitis	1/3672 (0%)		0/3643 (0%)
Gastric ulcer	4/3672 (0.1%)		2/3643 (0.1%)
Gastritis erosive	1/3672 (0%)		1/3643 (0%)
Gastroduodenal ulcer	0/3672 (0%)		1/3643 (0%)
Haematochezia	1/3672 (0%)		2/3643 (0.1%)
Haemorrhoids	1/3672 (0%)		0/3643 (0%)
Mouth haemorrhage	3/3672 (0.1%)		0/3643 (0%)
Pancreatitis	2/3672 (0.1%)		1/3643 (0%)
Retroperitoneal haemorrhage	2/3672 (0.1%)		2/3643 (0.1%)
Abdominal pain	5/3672 (0.1%)		2/3643 (0.1%)
Colonic polyp	1/3672 (0%)		0/3643 (0%)
Faeces discoloured	0/3672 (0%)		1/3643 (0%)
Gastritis	12/3672 (0.3%)		6/3643 (0.2%)
Haematemesis	5/3672 (0.1%)		4/3643 (0.1%)
Intestinal haemorrhage	0/3672 (0%)		1/3643 (0%)
Nausea	0/3672 (0%)		2/3643 (0.1%)
Rectal fissure	1/3672 (0%)		0/3643 (0%)
Diverticulum	2/3672 (0.1%)		1/3643 (0%)
Gastric polyps	0/3672 (0%)		1/3643 (0%)
Intestinal obstruction	1/3672 (0%)		1/3643 (0%)
Abdominal hernia	1/3672 (0%)		1/3643 (0%)
Constipation	1/3672 (0%)		1/3643 (0%)
Diarrhoea	1/3672 (0%)		1/3643 (0%)
Dysphagia	0/3672 (0%)		1/3643 (0%)
Gastrooesophageal reflux disease	2/3672 (0.1%)		1/3643 (0%)
Mechanical ileus	0/3672 (0%)		1/3643 (0%)
Melaena	4/3672 (0.1%)		1/3643 (0%)
Periodontitis	1/3672 (0%)		0/3643 (0%)
Vomiting	0/3672 (0%)		2/3643 (0.1%)
Abdominal pain upper	2/3672 (0.1%)		0/3643 (0%)
Colitis	1/3672 (0%)		0/3643 (0%)
Duodenal ulcer perforation	0/3672 (0%)		1/3643 (0%)
Gastric varices haemorrhage	1/3672 (0%)		0/3643 (0%)
Ileus	2/3672 (0.1%)		0/3643 (0%)
Inguinal hernia	1/3672 (0%)		0/3643 (0%)
Intestinal ischaemia	2/3672 (0.1%)		0/3643 (0%)
Reflux oesophagitis	0/3672 (0%)		1/3643 (0%)
General disorders
General physical health deterioration	0/3672 (0%)		1/3643 (0%)
Influenza like illness	0/3672 (0%)		1/3643 (0%)
Sudden death	19/3672 (0.5%)		13/3643 (0.4%)
Cardiac death	1/3672 (0%)		1/3643 (0%)
Discomfort	1/3672 (0%)		0/3643 (0%)
Generalised oedema	0/3672 (0%)		1/3643 (0%)
Oedema peripheral	1/3672 (0%)		0/3643 (0%)
Drug withdrawal syndrome	1/3672 (0%)		1/3643 (0%)
Ischaemic ulcer	1/3672 (0%)		0/3643 (0%)
Non-cardiac chest pain	38/3672 (1%)		46/3643 (1.3%)
Fatigue	0/3672 (0%)		1/3643 (0%)
Vessel puncture site haemorrhage	0/3672 (0%)		1/3643 (0%)
Asthenia	0/3672 (0%)		6/3643 (0.2%)
Death	11/3672 (0.3%)		8/3643 (0.2%)
Device dislocation	1/3672 (0%)		3/3643 (0.1%)
Chest pain	11/3672 (0.3%)		7/3643 (0.2%)
Pain	1/3672 (0%)		0/3643 (0%)
Pyrexia	3/3672 (0.1%)		1/3643 (0%)
Sudden cardiac death	10/3672 (0.3%)		11/3643 (0.3%)
Multi-organ failure	4/3672 (0.1%)		1/3643 (0%)
Hepatobiliary disorders
Hepatic steatosis	1/3672 (0%)		0/3643 (0%)
Cholangitis acute	1/3672 (0%)		0/3643 (0%)
Cholecystitis acute	5/3672 (0.1%)		1/3643 (0%)
Cholelithiasis	3/3672 (0.1%)		3/3643 (0.1%)
Bile duct stone	1/3672 (0%)		1/3643 (0%)
Biliary colic	0/3672 (0%)		1/3643 (0%)
Hepatic failure	0/3672 (0%)		1/3643 (0%)
Hepatic function abnormal	1/3672 (0%)		0/3643 (0%)
Hepatitis acute	0/3672 (0%)		1/3643 (0%)
Cholecystitis	6/3672 (0.2%)		3/3643 (0.1%)
Cholestasis	0/3672 (0%)		1/3643 (0%)
Immune system disorders
Sarcoidosis	2/3672 (0.1%)		0/3643 (0%)
Anaphylactic shock	1/3672 (0%)		0/3643 (0%)
Contrast media allergy	1/3672 (0%)		0/3643 (0%)
Drug hypersensitivity	0/3672 (0%)		1/3643 (0%)
Infections and infestations
Bacterial tracheitis	1/3672 (0%)		0/3643 (0%)
Erysipelas	0/3672 (0%)		1/3643 (0%)
Gastroenteritis viral	1/3672 (0%)		1/3643 (0%)
Mediastinitis	2/3672 (0.1%)		0/3643 (0%)
Pneumonia	35/3672 (1%)		35/3643 (1%)
Pneumonia bacterial	0/3672 (0%)		1/3643 (0%)
Post procedural infection	0/3672 (0%)		1/3643 (0%)
Upper respiratory tract infection	1/3672 (0%)		1/3643 (0%)
Viral infection	0/3672 (0%)		1/3643 (0%)
Arthritis infective	1/3672 (0%)		0/3643 (0%)
Cellulitis	4/3672 (0.1%)		6/3643 (0.2%)
Gangrene	1/3672 (0%)		4/3643 (0.1%)
Herpes zoster	0/3672 (0%)		1/3643 (0%)
Postoperative wound infection	2/3672 (0.1%)		5/3643 (0.1%)
Respiratory tract infection	1/3672 (0%)		0/3643 (0%)
Urinary tract infection	8/3672 (0.2%)		9/3643 (0.2%)
Bacteraemia	1/3672 (0%)		1/3643 (0%)
Cholecystitis infective	1/3672 (0%)		0/3643 (0%)
Diverticulitis	0/3672 (0%)		1/3643 (0%)
Respiratory tract infection viral	1/3672 (0%)		0/3643 (0%)
Sepsis	5/3672 (0.1%)		7/3643 (0.2%)
Staphylococcal infection	1/3672 (0%)		0/3643 (0%)
Chronic sinusitis	0/3672 (0%)		1/3643 (0%)
Endocarditis	1/3672 (0%)		2/3643 (0.1%)
Infective exacerbation of chronic obstructive airways disease	1/3672 (0%)		0/3643 (0%)
Intervertebral discitis	0/3672 (0%)		1/3643 (0%)
Osteomyelitis	1/3672 (0%)		0/3643 (0%)
Appendicitis	4/3672 (0.1%)		0/3643 (0%)
Epiglottitis	0/3672 (0%)		1/3643 (0%)
Lower respiratory tract infection	1/3672 (0%)		0/3643 (0%)
Pulmonary tuberculosis	0/3672 (0%)		1/3643 (0%)
Septic shock	4/3672 (0.1%)		2/3643 (0.1%)
Wound infection	1/3672 (0%)		0/3643 (0%)
Abscess limb	1/3672 (0%)		0/3643 (0%)
Device related sepsis	0/3672 (0%)		1/3643 (0%)
Encephalitis herpes	1/3672 (0%)		0/3643 (0%)
Gastroenteritis	3/3672 (0.1%)		5/3643 (0.1%)
Gastrointestinal infection	2/3672 (0.1%)		0/3643 (0%)
Injection site infection	0/3672 (0%)		1/3643 (0%)
Laryngitis	0/3672 (0%)		2/3643 (0.1%)
Skin infection	0/3672 (0%)		1/3643 (0%)
Bronchitis	6/3672 (0.2%)		1/3643 (0%)
Bronchopneumonia	0/3672 (0%)		2/3643 (0.1%)
Gallbladder empyema	1/3672 (0%)		0/3643 (0%)
Lobar pneumonia	1/3672 (0%)		0/3643 (0%)
Localised infection	0/3672 (0%)		3/3643 (0.1%)
Necrotising fasciitis	0/3672 (0%)		1/3643 (0%)
Pyelonephritis	2/3672 (0.1%)		1/3643 (0%)
Rectal abscess	0/3672 (0%)		1/3643 (0%)
Soft tissue infection	0/3672 (0%)		1/3643 (0%)
Staphylococcal bacteraemia	2/3672 (0.1%)		0/3643 (0%)
Tracheobronchitis	1/3672 (0%)		1/3643 (0%)
Urosepsis	3/3672 (0.1%)		0/3643 (0%)
Bacterial sepsis	1/3672 (0%)		0/3643 (0%)
Fungal skin infection	1/3672 (0%)		0/3643 (0%)
Infected bites	0/3672 (0%)		1/3643 (0%)
Sinusitis	0/3672 (0%)		1/3643 (0%)
Subcutaneous abscess	1/3672 (0%)		0/3643 (0%)
Injury, poisoning and procedural complications
Fall	5/3672 (0.1%)		4/3643 (0.1%)
Hip fracture	3/3672 (0.1%)		3/3643 (0.1%)
Incision site haemorrhage	1/3672 (0%)		0/3643 (0%)
Joint dislocation	1/3672 (0%)		0/3643 (0%)
Lumbar vertebral fracture	0/3672 (0%)		1/3643 (0%)
Overdose	2/3672 (0.1%)		0/3643 (0%)
Road traffic accident	0/3672 (0%)		1/3643 (0%)
Skull fractured base	1/3672 (0%)		0/3643 (0%)
Clavicle fracture	0/3672 (0%)		1/3643 (0%)
Procedural pain	1/3672 (0%)		0/3643 (0%)
Pubis fracture	1/3672 (0%)		0/3643 (0%)
Skin injury	1/3672 (0%)		0/3643 (0%)
Subdural haematoma	3/3672 (0.1%)		2/3643 (0.1%)
Tibia fracture	1/3672 (0%)		0/3643 (0%)
Ankle fracture	3/3672 (0.1%)		0/3643 (0%)
Postoperative thoracic procedure complication	1/3672 (0%)		0/3643 (0%)
Silicosis	0/3672 (0%)		1/3643 (0%)
Therapeutic agent toxicity	1/3672 (0%)		1/3643 (0%)
Incisional hernia, obstructive	2/3672 (0.1%)		0/3643 (0%)
Rib fracture	0/3672 (0%)		4/3643 (0.1%)
Animal bite	1/3672 (0%)		0/3643 (0%)
Coronary artery restenosis	2/3672 (0.1%)		1/3643 (0%)
Extradural haematoma	0/3672 (0%)		1/3643 (0%)
Fat embolism	1/3672 (0%)		0/3643 (0%)
Multiple fractures	0/3672 (0%)		1/3643 (0%)
Post procedural haemorrhage	2/3672 (0.1%)		0/3643 (0%)
Wound secretion	0/3672 (0%)		1/3643 (0%)
Brain contusion	0/3672 (0%)		1/3643 (0%)
Femoral neck fracture	0/3672 (0%)		2/3643 (0.1%)
Femur fracture	2/3672 (0.1%)		2/3643 (0.1%)
Foot fracture	1/3672 (0%)		0/3643 (0%)
Head injury	0/3672 (0%)		2/3643 (0.1%)
Incisional hernia	0/3672 (0%)		1/3643 (0%)
Joint injury	1/3672 (0%)		0/3643 (0%)
Soft tissue injury	0/3672 (0%)		1/3643 (0%)
Accidental overdose	5/3672 (0.1%)		2/3643 (0.1%)
Chest injury	1/3672 (0%)		0/3643 (0%)
Contusion	6/3672 (0.2%)		3/3643 (0.1%)
Drug toxicity	0/3672 (0%)		2/3643 (0.1%)
Facial bones fracture	0/3672 (0%)		1/3643 (0%)
Operative haemorrhage	1/3672 (0%)		1/3643 (0%)
Radius fracture	0/3672 (0%)		1/3643 (0%)
Vascular pseudoaneurysm	3/3672 (0.1%)		1/3643 (0%)
Wound	1/3672 (0%)		1/3643 (0%)
Arterial injury	1/3672 (0%)		0/3643 (0%)
In-stent coronary artery restenosis	7/3672 (0.2%)		7/3643 (0.2%)
Patella fracture	1/3672 (0%)		0/3643 (0%)
Investigations
Electrocardiogram QRS complex prolonged	1/3672 (0%)		0/3643 (0%)
Hepatic enzyme increased	2/3672 (0.1%)		2/3643 (0.1%)
Aspartate aminotransferase increased	0/3672 (0%)		2/3643 (0.1%)
Weight decreased	0/3672 (0%)		1/3643 (0%)
Clostridium test positive	0/3672 (0%)		1/3643 (0%)
Haemoglobin decreased	4/3672 (0.1%)		0/3643 (0%)
Occult blood positive	2/3672 (0.1%)		0/3643 (0%)
Alanine aminotransferase increased	0/3672 (0%)		2/3643 (0.1%)
Haematocrit decreased	1/3672 (0%)		0/3643 (0%)
Liver function test abnormal	1/3672 (0%)		1/3643 (0%)
Blood creatinine increased	0/3672 (0%)		1/3643 (0%)
Drug screen positive	1/3672 (0%)		0/3643 (0%)
Electrocardiogram QT prolonged	1/3672 (0%)		0/3643 (0%)
Metabolism and nutrition disorders
Diabetes mellitus	1/3672 (0%)		5/3643 (0.1%)
Gout	0/3672 (0%)		1/3643 (0%)
Metabolic acidosis	1/3672 (0%)		1/3643 (0%)
Vitamin B12 deficiency	1/3672 (0%)		1/3643 (0%)
Hyperglycaemia	3/3672 (0.1%)		3/3643 (0.1%)
Failure to thrive	1/3672 (0%)		0/3643 (0%)
Hypoglycaemia	5/3672 (0.1%)		8/3643 (0.2%)
Hyperkalaemia	2/3672 (0.1%)		4/3643 (0.1%)
Decreased appetite	1/3672 (0%)		0/3643 (0%)
Diabetic foot	2/3672 (0.1%)		0/3643 (0%)
Hypervolaemia	1/3672 (0%)		0/3643 (0%)
Hypokalaemia	3/3672 (0.1%)		0/3643 (0%)
Diabetic ketoacidosis	4/3672 (0.1%)		2/3643 (0.1%)
Electrolyte imbalance	0/3672 (0%)		1/3643 (0%)
Hyperglycaemic hyperosmolar nonketotic syndrome	0/3672 (0%)		1/3643 (0%)
Hyponatraemia	2/3672 (0.1%)		3/3643 (0.1%)
Iron deficiency	1/3672 (0%)		0/3643 (0%)
Fluid retention	1/3672 (0%)		0/3643 (0%)
Acidosis	0/3672 (0%)		1/3643 (0%)
Dehydration	4/3672 (0.1%)		4/3643 (0.1%)
Diabetes mellitus inadequate control	1/3672 (0%)		2/3643 (0.1%)
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion	1/3672 (0%)		0/3643 (0%)
Rhabdomyolysis	1/3672 (0%)		1/3643 (0%)
Arthralgia	1/3672 (0%)		0/3643 (0%)
Arthritis	0/3672 (0%)		2/3643 (0.1%)
Costochondritis	1/3672 (0%)		0/3643 (0%)
Muscle haemorrhage	3/3672 (0.1%)		0/3643 (0%)
Rotator cuff syndrome	1/3672 (0%)		1/3643 (0%)
Connective tissue disorder	1/3672 (0%)		0/3643 (0%)
Haemarthrosis	2/3672 (0.1%)		0/3643 (0%)
Musculoskeletal chest pain	6/3672 (0.2%)		4/3643 (0.1%)
Tenosynovitis	0/3672 (0%)		1/3643 (0%)
Muscular weakness	1/3672 (0%)		0/3643 (0%)
Neck pain	0/3672 (0%)		2/3643 (0.1%)
Periarthritis	1/3672 (0%)		1/3643 (0%)
Rheumatoid arthritis	1/3672 (0%)		0/3643 (0%)
Arthropathy	1/3672 (0%)		0/3643 (0%)
Back pain	2/3672 (0.1%)		7/3643 (0.2%)
Bursitis	1/3672 (0%)		0/3643 (0%)
Pain in extremity	3/3672 (0.1%)		0/3643 (0%)
Spinal osteoarthritis	1/3672 (0%)		0/3643 (0%)
Lumbar spinal stenosis	0/3672 (0%)		1/3643 (0%)
Musculoskeletal pain	1/3672 (0%)		4/3643 (0.1%)
Osteoarthritis	0/3672 (0%)		3/3643 (0.1%)
Spinal column stenosis	1/3672 (0%)		0/3643 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	1/3672 (0%)		2/3643 (0.1%)
Bile duct cancer	1/3672 (0%)		0/3643 (0%)
Breast cancer	1/3672 (0%)		0/3643 (0%)
Gastric cancer	5/3672 (0.1%)		2/3643 (0.1%)
Ovarian cancer	1/3672 (0%)		0/3643 (0%)
Rectal cancer	1/3672 (0%)		1/3643 (0%)
Thyroid neoplasm	0/3672 (0%)		1/3643 (0%)
Bladder neoplasm	1/3672 (0%)		0/3643 (0%)
Neoplasm	1/3672 (0%)		0/3643 (0%)
Neoplasm prostate	1/3672 (0%)		0/3643 (0%)
Non-small cell lung cancer stage IV	1/3672 (0%)		0/3643 (0%)
Tumour haemorrhage	1/3672 (0%)		0/3643 (0%)
Anal cancer stage IV	0/3672 (0%)		1/3643 (0%)
Pituitary tumour benign	1/3672 (0%)		0/3643 (0%)
Gastrointestinal carcinoma	1/3672 (0%)		0/3643 (0%)
Metastases to liver	1/3672 (0%)		0/3643 (0%)
Oesophageal adenocarcinoma	1/3672 (0%)		0/3643 (0%)
Pancreatic carcinoma	1/3672 (0%)		0/3643 (0%)
Prostate cancer	1/3672 (0%)		2/3643 (0.1%)
Lip neoplasm malignant stage unspecified	0/3672 (0%)		1/3643 (0%)
Small cell lung cancer stage unspecified	1/3672 (0%)		0/3643 (0%)
Glioblastoma	1/3672 (0%)		1/3643 (0%)
Renal cell carcinoma	1/3672 (0%)		0/3643 (0%)
Testis cancer recurrent	1/3672 (0%)		0/3643 (0%)
Bladder cancer	2/3672 (0.1%)		0/3643 (0%)
Bowen's disease	0/3672 (0%)		1/3643 (0%)
Endometrial cancer	1/3672 (0%)		0/3643 (0%)
Non-small cell lung cancer stage I	0/3672 (0%)		1/3643 (0%)
Adenocarcinoma pancreas	0/3672 (0%)		1/3643 (0%)
Bladder cancer stage II	1/3672 (0%)		0/3643 (0%)
Colon cancer	3/3672 (0.1%)		4/3643 (0.1%)
Lung neoplasm malignant	5/3672 (0.1%)		1/3643 (0%)
Lymphoma	0/3672 (0%)		1/3643 (0%)
Neoplasm malignant	0/3672 (0%)		1/3643 (0%)
Pancreatic carcinoma metastatic	2/3672 (0.1%)		0/3643 (0%)
Spinal meningioma benign	0/3672 (0%)		1/3643 (0%)
Squamous cell carcinoma of skin	1/3672 (0%)		1/3643 (0%)
Nervous system disorders
Cerebrovascular accident	20/3672 (0.5%)		39/3643 (1.1%)
Post herpetic neuralgia	0/3672 (0%)		1/3643 (0%)
Transient ischaemic attack	5/3672 (0.1%)		6/3643 (0.2%)
Carotid artery disease	1/3672 (0%)		0/3643 (0%)
Epilepsy	0/3672 (0%)		1/3643 (0%)
Headache	2/3672 (0.1%)		0/3643 (0%)
Hemiparesis	1/3672 (0%)		0/3643 (0%)
Metabolic encephalopathy	2/3672 (0.1%)		0/3643 (0%)
Polyneuropathy	1/3672 (0%)		0/3643 (0%)
Tremor	1/3672 (0%)		1/3643 (0%)
Basilar migraine	0/3672 (0%)		1/3643 (0%)
Spinal cord haemorrhage	1/3672 (0%)		0/3643 (0%)
Encephalopathy	2/3672 (0.1%)		0/3643 (0%)
Guillain-Barre syndrome	0/3672 (0%)		1/3643 (0%)
Spinal cord ischaemia	0/3672 (0%)		1/3643 (0%)
VIIth nerve paralysis	2/3672 (0.1%)		0/3643 (0%)
Carotid artery stenosis	5/3672 (0.1%)		2/3643 (0.1%)
Dizziness	4/3672 (0.1%)		6/3643 (0.2%)
Presyncope	2/3672 (0.1%)		3/3643 (0.1%)
Carotid artery occlusion	0/3672 (0%)		1/3643 (0%)
Haemorrhage intracranial	8/3672 (0.2%)		1/3643 (0%)
Syncope	13/3672 (0.4%)		14/3643 (0.4%)
Altered state of consciousness	2/3672 (0.1%)		0/3643 (0%)
Carotid arteriosclerosis	0/3672 (0%)		1/3643 (0%)
Convulsion	2/3672 (0.1%)		0/3643 (0%)
Dementia	1/3672 (0%)		0/3643 (0%)
Diabetic neuropathy	0/3672 (0%)		1/3643 (0%)
Intercostal neuralgia	1/3672 (0%)		0/3643 (0%)
Intraventricular haemorrhage	5/3672 (0.1%)		0/3643 (0%)
Mental retardation	0/3672 (0%)		1/3643 (0%)
Paraplegia	1/3672 (0%)		0/3643 (0%)
Sciatica	2/3672 (0.1%)		0/3643 (0%)
Subarachnoid haemorrhage	2/3672 (0.1%)		2/3643 (0.1%)
Psychiatric disorders
Bipolar I disorder	1/3672 (0%)		0/3643 (0%)
Anxiety	0/3672 (0%)		2/3643 (0.1%)
Psychotic disorder	0/3672 (0%)		1/3643 (0%)
Mental status changes	0/3672 (0%)		1/3643 (0%)
Suicide attempt	1/3672 (0%)		0/3643 (0%)
Major depression	0/3672 (0%)		1/3643 (0%)
Alcohol withdrawal syndrome	0/3672 (0%)		1/3643 (0%)
Confusional state	0/3672 (0%)		2/3643 (0.1%)
Completed suicide	0/3672 (0%)		1/3643 (0%)
Depression	0/3672 (0%)		4/3643 (0.1%)
Panic disorder	1/3672 (0%)		0/3643 (0%)
Renal and urinary disorders
Renal failure acute	17/3672 (0.5%)		10/3643 (0.3%)
Nephrolithiasis	2/3672 (0.1%)		1/3643 (0%)
Bladder diverticulum	0/3672 (0%)		1/3643 (0%)
Dysuria	2/3672 (0.1%)		0/3643 (0%)
Renal injury	0/3672 (0%)		1/3643 (0%)
Calculus bladder	1/3672 (0%)		0/3643 (0%)
Renal failure	8/3672 (0.2%)		5/3643 (0.1%)
Renal infarct	1/3672 (0%)		0/3643 (0%)
Haematuria	13/3672 (0.4%)		5/3643 (0.1%)
Acute prerenal failure	2/3672 (0.1%)		0/3643 (0%)
Renal impairment	5/3672 (0.1%)		6/3643 (0.2%)
Hydronephrosis	1/3672 (0%)		0/3643 (0%)
Nephropathy	0/3672 (0%)		1/3643 (0%)
Nephropathy toxic	3/3672 (0.1%)		0/3643 (0%)
Renal colic	0/3672 (0%)		1/3643 (0%)
Renal failure chronic	3/3672 (0.1%)		2/3643 (0.1%)
Urethral stenosis	0/3672 (0%)		1/3643 (0%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	0/3672 (0%)		1/3643 (0%)
Vaginal haemorrhage	1/3672 (0%)		0/3643 (0%)
Prostatomegaly	1/3672 (0%)		0/3643 (0%)
Balanoposthitis	1/3672 (0%)		0/3643 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	1/3672 (0%)		2/3643 (0.1%)
Bronchitis chronic	0/3672 (0%)		1/3643 (0%)
Pulmonary hypertension	0/3672 (0%)		1/3643 (0%)
Acute pulmonary oedema	5/3672 (0.1%)		7/3643 (0.2%)
Dyspnoea	4/3672 (0.1%)		4/3643 (0.1%)
Hypercapnia	0/3672 (0%)		1/3643 (0%)
Pulmonary embolism	3/3672 (0.1%)		6/3643 (0.2%)
Dyspnoea exertional	0/3672 (0%)		1/3643 (0%)
Haemothorax	3/3672 (0.1%)		0/3643 (0%)
Respiratory distress	1/3672 (0%)		0/3643 (0%)
Respiratory failure	2/3672 (0.1%)		3/3643 (0.1%)
Lung disorder	0/3672 (0%)		1/3643 (0%)
Pleural effusion	4/3672 (0.1%)		6/3643 (0.2%)
Pneumomediastinum	0/3672 (0%)		1/3643 (0%)
Asthma	1/3672 (0%)		2/3643 (0.1%)
Bronchospasm	0/3672 (0%)		1/3643 (0%)
Interstitial lung disease	0/3672 (0%)		1/3643 (0%)
Laryngeal hypertrophy	0/3672 (0%)		1/3643 (0%)
Pulmonary congestion	0/3672 (0%)		1/3643 (0%)
Pulmonary oedema	9/3672 (0.2%)		3/3643 (0.1%)
Chronic obstructive pulmonary disease	14/3672 (0.4%)		8/3643 (0.2%)
Cough	0/3672 (0%)		1/3643 (0%)
Haemoptysis	2/3672 (0.1%)		2/3643 (0.1%)
Hypoxia	0/3672 (0%)		1/3643 (0%)
Pulmonary artery thrombosis	1/3672 (0%)		0/3643 (0%)
Bronchial disorder	0/3672 (0%)		1/3643 (0%)
Epistaxis	5/3672 (0.1%)		5/3643 (0.1%)
Pleuritic pain	1/3672 (0%)		0/3643 (0%)
Skin and subcutaneous tissue disorders
Actinic keratosis	0/3672 (0%)		1/3643 (0%)
Rash papular	0/3672 (0%)		1/3643 (0%)
Rash pruritic	1/3672 (0%)		0/3643 (0%)
Toxic skin eruption	0/3672 (0%)		1/3643 (0%)
Skin necrosis	0/3672 (0%)		1/3643 (0%)
Urticaria	0/3672 (0%)		1/3643 (0%)
Dermatitis	0/3672 (0%)		1/3643 (0%)
Skin ulcer	2/3672 (0.1%)		0/3643 (0%)
Dermatomyositis	0/3672 (0%)		1/3643 (0%)
Vascular disorders
Embolism arterial	0/3672 (0%)		2/3643 (0.1%)
Extravasation blood	1/3672 (0%)		0/3643 (0%)
Hypertension	16/3672 (0.4%)		13/3643 (0.4%)
Peripheral ischaemia	3/3672 (0.1%)		1/3643 (0%)
Vasospasm	1/3672 (0%)		0/3643 (0%)
Aortic dissection	1/3672 (0%)		0/3643 (0%)
Aortic stenosis	1/3672 (0%)		1/3643 (0%)
Arteriosclerosis obliterans	0/3672 (0%)		1/3643 (0%)
Jugular vein thrombosis	0/3672 (0%)		1/3643 (0%)
Orthostatic hypotension	2/3672 (0.1%)		0/3643 (0%)
Thrombosis	0/3672 (0%)		1/3643 (0%)
Accelerated hypertension	0/3672 (0%)		2/3643 (0.1%)
Hypertensive crisis	5/3672 (0.1%)		4/3643 (0.1%)
Hypotension	5/3672 (0.1%)		3/3643 (0.1%)
Leriche syndrome	0/3672 (0%)		1/3643 (0%)
Thrombophlebitis	0/3672 (0%)		1/3643 (0%)
Arterial thrombosis	1/3672 (0%)		0/3643 (0%)
Arteriosclerosis	2/3672 (0.1%)		0/3643 (0%)
Artery dissection	1/3672 (0%)		0/3643 (0%)
Femoral arterial stenosis	0/3672 (0%)		1/3643 (0%)
Peripheral vascular disorder	1/3672 (0%)		9/3643 (0.2%)
Aortic aneurysm	0/3672 (0%)		1/3643 (0%)
Arterial stenosis	1/3672 (0%)		0/3643 (0%)
Femoral artery occlusion	2/3672 (0.1%)		0/3643 (0%)
Intermittent claudication	1/3672 (0%)		3/3643 (0.1%)
Peripheral embolism	0/3672 (0%)		2/3643 (0.1%)
Ischaemia	1/3672 (0%)		0/3643 (0%)
Peripheral artery aneurysm	1/3672 (0%)		0/3643 (0%)
Deep vein thrombosis	3/3672 (0.1%)		1/3643 (0%)
Femoral artery aneurysm	1/3672 (0%)		0/3643 (0%)
Haematoma	14/3672 (0.4%)		5/3643 (0.1%)
Haemorrhage	1/3672 (0%)		0/3643 (0%)
Arterial thrombosis limb	1/3672 (0%)		1/3643 (0%)
Circulatory collapse	0/3672 (0%)		1/3643 (0%)
Hypertensive emergency	1/3672 (0%)		0/3643 (0%)
Peripheral arterial occlusive disease	4/3672 (0.1%)		4/3643 (0.1%)
Other (Not Including Serious) Adverse Events
	Apixaban 5 mg BID		Placebo BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	357/3672 (9.7%)		231/3643 (6.3%)
General disorders
Chest pain	186/3672 (5.1%)		173/3643 (4.7%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	186/3672 (5.1%)		63/3643 (1.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.