Trial Outcomes & Findings for Phase III Acute Coronary Syndrome (NCT NCT00831441)
NCT ID: NCT00831441
Last Updated: 2016-01-27
Results Overview
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).
Recruitment status
TERMINATED
Study phase
PHASE3
Target enrollment
7484 participants
Primary outcome timeframe
Randomization (Day 1) to first event (CV death, MI, ischemic stroke), up to March 2011, approximately 2 years
Results posted on
2016-01-27
Participant Flow
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.
Participant milestones
| Measure |
Placebo BID
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 5 mg BID
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.
|
|---|---|---|
|
Randomized
STARTED
|
3687
|
3705
|
|
Randomized
Treated
|
3643
|
3672
|
|
Randomized
COMPLETED
|
0
|
0
|
|
Randomized
NOT COMPLETED
|
3687
|
3705
|
|
Follow Up (30 Days)
STARTED
|
3508
|
3529
|
|
Follow Up (30 Days)
COMPLETED
|
3375
|
3355
|
|
Follow Up (30 Days)
NOT COMPLETED
|
133
|
174
|
Reasons for withdrawal
| Measure |
Placebo BID
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 5 mg BID
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.
|
|---|---|---|
|
Randomized
Death
|
82
|
81
|
|
Randomized
Adverse Event
|
248
|
321
|
|
Randomized
Emergency procedure
|
2
|
2
|
|
Randomized
Elective procedure
|
26
|
25
|
|
Randomized
Physician Decision
|
26
|
35
|
|
Randomized
No longer met criteria
|
13
|
19
|
|
Randomized
Withdrawal by Subject
|
178
|
212
|
|
Randomized
Lost to Follow-up
|
26
|
35
|
|
Randomized
Administrative reason by sponsor
|
2780
|
2671
|
|
Randomized
poor/non-compliance
|
30
|
38
|
|
Randomized
non-specified
|
276
|
266
|
|
Follow Up (30 Days)
Withdrawal by Subject
|
41
|
34
|
|
Follow Up (30 Days)
Lost to Follow-up
|
13
|
27
|
|
Follow Up (30 Days)
Death
|
63
|
86
|
|
Follow Up (30 Days)
non-specified
|
16
|
26
|
|
Follow Up (30 Days)
missing end of study status
|
0
|
1
|
Baseline Characteristics
Phase III Acute Coronary Syndrome
Baseline characteristics by cohort
| Measure |
Placebo
n=3687 Participants
Placebo: Tablets, Oral, 0 mg, twice daily.
|
Apixaban 5 mg BID
n=3705 Participants
Apixaban: Tablets, Oral, 5 mg, twice daily.
|
Total
n=7392 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
65.4 years
STANDARD_DEVIATION 11.05 • n=5 Participants
|
65.3 years
STANDARD_DEVIATION 10.89 • n=7 Participants
|
65.4 years
STANDARD_DEVIATION 10.97 • n=5 Participants
|
|
Age, Customized
< 65 years
|
1512 participants
n=5 Participants
|
1526 participants
n=7 Participants
|
3038 participants
n=5 Participants
|
|
Age, Customized
≥ 65 and < 75 years
|
1420 participants
n=5 Participants
|
1440 participants
n=7 Participants
|
2860 participants
n=5 Participants
|
|
Age, Customized
≥ 75 years
|
755 participants
n=5 Participants
|
739 participants
n=7 Participants
|
1494 participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
1169 Participants
n=5 Participants
|
1209 Participants
n=7 Participants
|
2378 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
2518 Participants
n=5 Participants
|
2496 Participants
n=7 Participants
|
5014 Participants
n=5 Participants
|
|
Region of Enrollment
Russian Federation
|
540 participants
n=5 Participants
|
542 participants
n=7 Participants
|
1082 participants
n=5 Participants
|
|
Region of Enrollment
Puerto Rico
|
13 participants
n=5 Participants
|
17 participants
n=7 Participants
|
30 participants
n=5 Participants
|
|
Region of Enrollment
Singapore
|
11 participants
n=5 Participants
|
14 participants
n=7 Participants
|
25 participants
n=5 Participants
|
|
Region of Enrollment
United States
|
450 participants
n=5 Participants
|
455 participants
n=7 Participants
|
905 participants
n=5 Participants
|
|
Region of Enrollment
Austria
|
58 participants
n=5 Participants
|
56 participants
n=7 Participants
|
114 participants
n=5 Participants
|
|
Region of Enrollment
Sweden
|
50 participants
n=5 Participants
|
55 participants
n=7 Participants
|
105 participants
n=5 Participants
|
|
Region of Enrollment
Netherlands
|
45 participants
n=5 Participants
|
52 participants
n=7 Participants
|
97 participants
n=5 Participants
|
|
Region of Enrollment
China
|
36 participants
n=5 Participants
|
39 participants
n=7 Participants
|
75 participants
n=5 Participants
|
|
Region of Enrollment
Poland
|
176 participants
n=5 Participants
|
177 participants
n=7 Participants
|
353 participants
n=5 Participants
|
|
Region of Enrollment
Korea, Republic of
|
88 participants
n=5 Participants
|
89 participants
n=7 Participants
|
177 participants
n=5 Participants
|
|
Region of Enrollment
Brazil
|
125 participants
n=5 Participants
|
125 participants
n=7 Participants
|
250 participants
n=5 Participants
|
|
Region of Enrollment
Slovakia
|
30 participants
n=5 Participants
|
29 participants
n=7 Participants
|
59 participants
n=5 Participants
|
|
Region of Enrollment
France
|
22 participants
n=5 Participants
|
18 participants
n=7 Participants
|
40 participants
n=5 Participants
|
|
Region of Enrollment
Bulgaria
|
100 participants
n=5 Participants
|
102 participants
n=7 Participants
|
202 participants
n=5 Participants
|
|
Region of Enrollment
Chile
|
30 participants
n=5 Participants
|
26 participants
n=7 Participants
|
56 participants
n=5 Participants
|
|
Region of Enrollment
Colombia
|
45 participants
n=5 Participants
|
43 participants
n=7 Participants
|
88 participants
n=5 Participants
|
|
Region of Enrollment
Argentina
|
131 participants
n=5 Participants
|
125 participants
n=7 Participants
|
256 participants
n=5 Participants
|
|
Region of Enrollment
Romania
|
78 participants
n=5 Participants
|
80 participants
n=7 Participants
|
158 participants
n=5 Participants
|
|
Region of Enrollment
Hungary
|
121 participants
n=5 Participants
|
120 participants
n=7 Participants
|
241 participants
n=5 Participants
|
|
Region of Enrollment
Japan
|
91 participants
n=5 Participants
|
95 participants
n=7 Participants
|
186 participants
n=5 Participants
|
|
Region of Enrollment
Ukraine
|
128 participants
n=5 Participants
|
130 participants
n=7 Participants
|
258 participants
n=5 Participants
|
|
Region of Enrollment
United Kingdom
|
24 participants
n=5 Participants
|
21 participants
n=7 Participants
|
45 participants
n=5 Participants
|
|
Region of Enrollment
Switzerland
|
18 participants
n=5 Participants
|
20 participants
n=7 Participants
|
38 participants
n=5 Participants
|
|
Region of Enrollment
India
|
396 participants
n=5 Participants
|
398 participants
n=7 Participants
|
794 participants
n=5 Participants
|
|
Region of Enrollment
Spain
|
81 participants
n=5 Participants
|
79 participants
n=7 Participants
|
160 participants
n=5 Participants
|
|
Region of Enrollment
New Zealand
|
13 participants
n=5 Participants
|
9 participants
n=7 Participants
|
22 participants
n=5 Participants
|
|
Region of Enrollment
Canada
|
126 participants
n=5 Participants
|
128 participants
n=7 Participants
|
254 participants
n=5 Participants
|
|
Region of Enrollment
Czech Republic
|
54 participants
n=5 Participants
|
54 participants
n=7 Participants
|
108 participants
n=5 Participants
|
|
Region of Enrollment
Turkey
|
9 participants
n=5 Participants
|
11 participants
n=7 Participants
|
20 participants
n=5 Participants
|
|
Region of Enrollment
Belgium
|
47 participants
n=5 Participants
|
50 participants
n=7 Participants
|
97 participants
n=5 Participants
|
|
Region of Enrollment
Norway
|
26 participants
n=5 Participants
|
25 participants
n=7 Participants
|
51 participants
n=5 Participants
|
|
Region of Enrollment
Finland
|
4 participants
n=5 Participants
|
3 participants
n=7 Participants
|
7 participants
n=5 Participants
|
|
Region of Enrollment
Denmark
|
37 participants
n=5 Participants
|
34 participants
n=7 Participants
|
71 participants
n=5 Participants
|
|
Region of Enrollment
Italy
|
23 participants
n=5 Participants
|
21 participants
n=7 Participants
|
44 participants
n=5 Participants
|
|
Region of Enrollment
South Africa
|
66 participants
n=5 Participants
|
67 participants
n=7 Participants
|
133 participants
n=5 Participants
|
|
Region of Enrollment
Mexico
|
161 participants
n=5 Participants
|
161 participants
n=7 Participants
|
322 participants
n=5 Participants
|
|
Region of Enrollment
Israel
|
73 participants
n=5 Participants
|
66 participants
n=7 Participants
|
139 participants
n=5 Participants
|
|
Region of Enrollment
Australia
|
15 participants
n=5 Participants
|
23 participants
n=7 Participants
|
38 participants
n=5 Participants
|
|
Region of Enrollment
Peru
|
66 participants
n=5 Participants
|
66 participants
n=7 Participants
|
132 participants
n=5 Participants
|
|
Region of Enrollment
Germany
|
80 participants
n=5 Participants
|
80 participants
n=7 Participants
|
160 participants
n=5 Participants
|
|
Antiplatelet Therapy
Dual Antiplatelet Therapy
|
2965 participants
n=5 Participants
|
2968 participants
n=7 Participants
|
5933 participants
n=5 Participants
|
|
Antiplatelet Therapy
Single Antiplatelet Therapy
|
722 participants
n=5 Participants
|
737 participants
n=7 Participants
|
1459 participants
n=5 Participants
|
|
ACS Index Event
STEMI
|
1412 participants
n=5 Participants
|
1426 participants
n=7 Participants
|
2838 participants
n=5 Participants
|
|
ACS Index Event
non-STEMI
|
1582 participants
n=5 Participants
|
1581 participants
n=7 Participants
|
3163 participants
n=5 Participants
|
|
ACS Index Event
Unstable angina
|
693 participants
n=5 Participants
|
698 participants
n=7 Participants
|
1391 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Randomization (Day 1) to first event (CV death, MI, ischemic stroke), up to March 2011, approximately 2 yearsPopulation: All randomized participants were analyzed.
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).
Outcome measures
| Measure |
Placebo
n=3687 Participants
Placebo: Tablets, Oral, 0 mg, twice daily.
|
Apixaban 5 mg BID
n=3705 Participants
Apixaban: Tablets, Oral, 5 mg, twice daily. Study was terminated in Year 2.
|
|---|---|---|
|
Event Rate of Cardiovascular Death, Myocardial Infarction, or Ischemic Stroke During the Intended Treatment Period - Randomized Participants
|
13.96 percentage of participants/100-pt years
|
13.20 percentage of participants/100-pt years
|
PRIMARY outcome
Timeframe: 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 yearsPopulation: All participants who received at least one dose of blinded study drug and signed informed consent were analyzed.
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.
Outcome measures
| Measure |
Placebo
n=3643 Participants
Placebo: Tablets, Oral, 0 mg, twice daily.
|
Apixaban 5 mg BID
n=3672 Participants
Apixaban: Tablets, Oral, 5 mg, twice daily. Study was terminated in Year 2.
|
|---|---|---|
|
Event Rate of Confirmed Major Bleeding Using Thrombolysis in Myocardial Infarction (TIMI) Criteria During the Treatment Period - Treated Participants
|
0.91 percentage of participants/100-pt years
|
2.40 percentage of participants/100-pt years
|
SECONDARY outcome
Timeframe: Randomization (Day 1) to first event of UA, up to March 2011, approximately 2 yearsPopulation: All randomized participants were analyzed.
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).
Outcome measures
| Measure |
Placebo
n=3687 Participants
Placebo: Tablets, Oral, 0 mg, twice daily.
|
Apixaban 5 mg BID
n=3705 Participants
Apixaban: Tablets, Oral, 5 mg, twice daily. Study was terminated in Year 2.
|
|---|---|---|
|
Event Rate of Unstable Angina (UA) During the Intended Treatment Period - Randomized Participants
|
4.21 percentage of participants/100-pt years
|
3.95 percentage of participants/100-pt years
|
SECONDARY outcome
Timeframe: Randomization (Day 1) to first event (stroke), up to March 2011, approximately 2 yearsPopulation: All randomized participants were analyzed.
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).
Outcome measures
| Measure |
Placebo
n=3687 Participants
Placebo: Tablets, Oral, 0 mg, twice daily.
|
Apixaban 5 mg BID
n=3705 Participants
Apixaban: Tablets, Oral, 5 mg, twice daily. Study was terminated in Year 2.
|
|---|---|---|
|
Event Rate of Stroke During the Intended Treatment Period - Randomized Participants
|
1.85 percentage of participants/100-pt years
|
1.65 percentage of participants/100-pt years
|
SECONDARY outcome
Timeframe: Randomization (Day 1) to first event (MI), up to March 2011, approximately 2 yearsPopulation: All randomized participants were analyzed.
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.
Outcome measures
| Measure |
Placebo
n=3687 Participants
Placebo: Tablets, Oral, 0 mg, twice daily.
|
Apixaban 5 mg BID
n=3705 Participants
Apixaban: Tablets, Oral, 5 mg, twice daily. Study was terminated in Year 2.
|
|---|---|---|
|
Event Rate of Myocardial Infarction (MI) During the Intended Treatment Period - Randomized Participants
|
9.20 percentage of participants/100-pt years
|
8.59 percentage of participants/100-pt years
|
SECONDARY outcome
Timeframe: Randomization (Day 1) to first event (stent thrombosis), up to March 2011, approximately 2 yearsPopulation: All randomized participants were analyzed.
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.
Outcome measures
| Measure |
Placebo
n=3687 Participants
Placebo: Tablets, Oral, 0 mg, twice daily.
|
Apixaban 5 mg BID
n=3705 Participants
Apixaban: Tablets, Oral, 5 mg, twice daily. Study was terminated in Year 2.
|
|---|---|---|
|
Event Rate of Stent Thrombosis During the Intended Treatment Period - Randomized Participants
|
2.21 percentage of participants/100-pt years
|
1.61 percentage of participants/100-pt years
|
SECONDARY outcome
Timeframe: Randomization (Day 1) to first event (CV death, MI, UA, Ischemic Stroke, up to March 2011, approximately 2 yearsPopulation: All randomized participants were analyzed.
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).
Outcome measures
| Measure |
Placebo
n=3687 Participants
Placebo: Tablets, Oral, 0 mg, twice daily.
|
Apixaban 5 mg BID
n=3705 Participants
Apixaban: Tablets, Oral, 5 mg, twice daily. Study was terminated in Year 2.
|
|---|---|---|
|
Event Rate of Composite of Cardiovascular Death, Myocardial Infarction, Unstable Angina, or Ischemic Stroke During the Intended Treatment Period - Randomized Participants
|
17.95 percentage of participants/100-pt years
|
16.92 percentage of participants/100-pt years
|
SECONDARY outcome
Timeframe: Randomization (Day 1) to first event (CV death, Fatal Bleed, MI, or stroke), up to March 2011, approximately 2 yearsPopulation: All randomized participants were analyzed.
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).
Outcome measures
| Measure |
Placebo
n=3687 Participants
Placebo: Tablets, Oral, 0 mg, twice daily.
|
Apixaban 5 mg BID
n=3705 Participants
Apixaban: Tablets, Oral, 5 mg, twice daily. Study was terminated in Year 2.
|
|---|---|---|
|
Event Rate of Composite of Cardiovascular Death, Fatal Bleed, Myocardial Infarction, or Stroke During the Intended Treatment Period - Randomized Participants
|
14.27 percentage of participants/100-pt years
|
13.97 percentage of participants/100-pt years
|
SECONDARY outcome
Timeframe: Randomization (Day 1) to first event (All Cause Death, MI, or Stroke), up to March 2011, approximately 2 yearsPopulation: All randomized participants were analyzed.
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).
Outcome measures
| Measure |
Placebo
n=3687 Participants
Placebo: Tablets, Oral, 0 mg, twice daily.
|
Apixaban 5 mg BID
n=3705 Participants
Apixaban: Tablets, Oral, 5 mg, twice daily. Study was terminated in Year 2.
|
|---|---|---|
|
Event Rate of Composite of All-Cause Death, Myocardial Infarction, or Stroke During the Intended Treatment Period - Randomized Participants
|
15.65 percentage of participants/100-pt years
|
15.48 percentage of participants/100-pt years
|
SECONDARY outcome
Timeframe: 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 yearsPopulation: All participants who received at least one dose of blinded study drug and signed informed consent were analyzed.
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.
Outcome measures
| Measure |
Placebo
n=3643 Participants
Placebo: Tablets, Oral, 0 mg, twice daily.
|
Apixaban 5 mg BID
n=3672 Participants
Apixaban: Tablets, Oral, 5 mg, twice daily. Study was terminated in Year 2.
|
|---|---|---|
|
Event Rate of Confirmed Major Bleeding Using International Society on Thrombosis and Hemostasis (ISTH) Criteria During the Treatment Period - Treated Participants
|
2.04 percentage of participants/100-pt years
|
5.13 percentage of participants/100-pt years
|
SECONDARY outcome
Timeframe: 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 yearsPopulation: All participants who received at least one dose of blinded study drug and signed informed consent were analyzed.
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.
Outcome measures
| Measure |
Placebo
n=3643 Participants
Placebo: Tablets, Oral, 0 mg, twice daily.
|
Apixaban 5 mg BID
n=3672 Participants
Apixaban: Tablets, Oral, 5 mg, twice daily. Study was terminated in Year 2.
|
|---|---|---|
|
Event Rate of Confirmed Major Bleeding or Clinically Relevant Non-Major Bleeding (CRNM) Using ISTH Criteria During the Treatment Period - Treated Participants
|
2.29 percentage of participants/100-pt years
|
6.15 percentage of participants/100-pt years
|
SECONDARY outcome
Timeframe: 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 yearsPopulation: All participants who received at least one dose of blinded study drug and signed informed consent were analyzed.
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.
Outcome measures
| Measure |
Placebo
n=3643 Participants
Placebo: Tablets, Oral, 0 mg, twice daily.
|
Apixaban 5 mg BID
n=3672 Participants
Apixaban: Tablets, Oral, 5 mg, twice daily. Study was terminated in Year 2.
|
|---|---|---|
|
Event Rate of All Bleeding Reported by the Investigator During the Treatment Period - Treated Participants
|
16.33 percentage of participants/100-pt years
|
39.98 percentage of participants/100-pt years
|
Adverse Events
Apixaban 5 mg BID
Serious events: 894 serious events
Other events: 357 other events
Deaths: 0 deaths
Placebo BID
Serious events: 884 serious events
Other events: 231 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Apixaban 5 mg BID
n=3672 participants at risk
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 BID
n=3643 participants at risk
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.
|
|---|---|---|
|
Injury, poisoning and procedural complications
Subdural haematoma
|
0.08%
3/3672
|
0.05%
2/3643
|
|
Skin and subcutaneous tissue disorders
Actinic keratosis
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
0.03%
1/3672
|
0.05%
2/3643
|
|
Cardiac disorders
Arteriospasm coronary
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Cardiac disorders
Atrial flutter
|
0.05%
2/3672
|
0.05%
2/3643
|
|
Infections and infestations
Bacterial tracheitis
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
|
0.03%
1/3672
|
0.05%
2/3643
|
|
Reproductive system and breast disorders
Benign prostatic hyperplasia
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bile duct cancer
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Psychiatric disorders
Bipolar I disorder
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Respiratory, thoracic and mediastinal disorders
Bronchitis chronic
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Cardiac disorders
Cardiac failure acute
|
0.16%
6/3672
|
0.08%
3/3643
|
|
Cardiac disorders
Cardiac failure congestive
|
0.44%
16/3672
|
0.47%
17/3643
|
|
Cardiac disorders
Cardiomyopathy
|
0.05%
2/3672
|
0.03%
1/3643
|
|
Nervous system disorders
Cerebrovascular accident
|
0.54%
20/3672
|
1.1%
39/3643
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
0.03%
1/3672
|
0.14%
5/3643
|
|
Investigations
Electrocardiogram QRS complex prolonged
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Vascular disorders
Embolism arterial
|
0.00%
0/3672
|
0.05%
2/3643
|
|
Infections and infestations
Erysipelas
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Vascular disorders
Extravasation blood
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Injury, poisoning and procedural complications
Fall
|
0.14%
5/3672
|
0.11%
4/3643
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastric cancer
|
0.14%
5/3672
|
0.05%
2/3643
|
|
Infections and infestations
Gastroenteritis viral
|
0.03%
1/3672
|
0.03%
1/3643
|
|
General disorders
General physical health deterioration
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Metabolism and nutrition disorders
Gout
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Investigations
Hepatic enzyme increased
|
0.05%
2/3672
|
0.05%
2/3643
|
|
Hepatobiliary disorders
Hepatic steatosis
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Injury, poisoning and procedural complications
Hip fracture
|
0.08%
3/3672
|
0.08%
3/3643
|
|
Vascular disorders
Hypertension
|
0.44%
16/3672
|
0.36%
13/3643
|
|
Injury, poisoning and procedural complications
Incision site haemorrhage
|
0.03%
1/3672
|
0.00%
0/3643
|
|
General disorders
Influenza like illness
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Cardiac disorders
Interventricular septum rupture
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Blood and lymphatic system disorders
Iron deficiency anaemia
|
0.00%
0/3672
|
0.05%
2/3643
|
|
Injury, poisoning and procedural complications
Joint dislocation
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Injury, poisoning and procedural complications
Lumbar vertebral fracture
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Infections and infestations
Mediastinitis
|
0.05%
2/3672
|
0.00%
0/3643
|
|
Metabolism and nutrition disorders
Metabolic acidosis
|
0.03%
1/3672
|
0.03%
1/3643
|
|
Gastrointestinal disorders
Oesophageal ulcer
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Gastrointestinal disorders
Oesophagitis
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Ovarian cancer
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Injury, poisoning and procedural complications
Overdose
|
0.05%
2/3672
|
0.00%
0/3643
|
|
Vascular disorders
Peripheral ischaemia
|
0.08%
3/3672
|
0.03%
1/3643
|
|
Infections and infestations
Pneumonia
|
0.95%
35/3672
|
0.96%
35/3643
|
|
Infections and infestations
Pneumonia bacterial
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Nervous system disorders
Post herpetic neuralgia
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Infections and infestations
Post procedural infection
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary hypertension
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Skin and subcutaneous tissue disorders
Rash papular
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Rectal cancer
|
0.03%
1/3672
|
0.03%
1/3643
|
|
Musculoskeletal and connective tissue disorders
Rhabdomyolysis
|
0.03%
1/3672
|
0.03%
1/3643
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Immune system disorders
Sarcoidosis
|
0.05%
2/3672
|
0.00%
0/3643
|
|
Injury, poisoning and procedural complications
Skull fractured base
|
0.03%
1/3672
|
0.00%
0/3643
|
|
General disorders
Sudden death
|
0.52%
19/3672
|
0.36%
13/3643
|
|
Cardiac disorders
Supraventricular extrasystoles
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.03%
1/3672
|
0.03%
1/3643
|
|
Gastrointestinal disorders
Thrombosis mesenteric vessel
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Thyroid neoplasm
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Nervous system disorders
Transient ischaemic attack
|
0.14%
5/3672
|
0.16%
6/3643
|
|
Infections and infestations
Upper respiratory tract infection
|
0.03%
1/3672
|
0.03%
1/3643
|
|
Vascular disorders
Vasospasm
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Infections and infestations
Viral infection
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Metabolism and nutrition disorders
Vitamin B12 deficiency
|
0.03%
1/3672
|
0.03%
1/3643
|
|
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema
|
0.14%
5/3672
|
0.19%
7/3643
|
|
Immune system disorders
Anaphylactic shock
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Cardiac disorders
Angina pectoris
|
1.0%
37/3672
|
1.1%
41/3643
|
|
Vascular disorders
Aortic dissection
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Vascular disorders
Aortic stenosis
|
0.03%
1/3672
|
0.03%
1/3643
|
|
Vascular disorders
Arteriosclerosis obliterans
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
0.00%
0/3672
|
0.05%
2/3643
|
|
Infections and infestations
Arthritis infective
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Cardiac disorders
Atrioventricular block
|
0.03%
1/3672
|
0.03%
1/3643
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder neoplasm
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Cardiac disorders
Bundle branch block left
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Cardiac disorders
Cardiac arrest
|
0.11%
4/3672
|
0.11%
4/3643
|
|
General disorders
Cardiac death
|
0.03%
1/3672
|
0.03%
1/3643
|
|
Cardiac disorders
Cardiac failure chronic
|
0.03%
1/3672
|
0.08%
3/3643
|
|
Nervous system disorders
Carotid artery disease
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Eye disorders
Cataract
|
0.03%
1/3672
|
0.11%
4/3643
|
|
Infections and infestations
Cellulitis
|
0.11%
4/3672
|
0.16%
6/3643
|
|
Hepatobiliary disorders
Cholangitis acute
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.14%
5/3672
|
0.03%
1/3643
|
|
Injury, poisoning and procedural complications
Clavicle fracture
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Musculoskeletal and connective tissue disorders
Costochondritis
|
0.03%
1/3672
|
0.00%
0/3643
|
|
General disorders
Discomfort
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Gastrointestinal disorders
Duodenal ulcer
|
0.05%
2/3672
|
0.00%
0/3643
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.11%
4/3672
|
0.11%
4/3643
|
|
Nervous system disorders
Epilepsy
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Infections and infestations
Gangrene
|
0.03%
1/3672
|
0.11%
4/3643
|
|
General disorders
Generalised oedema
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Nervous system disorders
Headache
|
0.05%
2/3672
|
0.00%
0/3643
|
|
Nervous system disorders
Hemiparesis
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Infections and infestations
Herpes zoster
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Respiratory, thoracic and mediastinal disorders
Hypercapnia
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.08%
3/3672
|
0.08%
3/3643
|
|
Gastrointestinal disorders
Impaired gastric emptying
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Gastrointestinal disorders
Irritable bowel syndrome
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Vascular disorders
Jugular vein thrombosis
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Nervous system disorders
Metabolic encephalopathy
|
0.05%
2/3672
|
0.00%
0/3643
|
|
Musculoskeletal and connective tissue disorders
Muscle haemorrhage
|
0.08%
3/3672
|
0.00%
0/3643
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm prostate
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Non-small cell lung cancer stage IV
|
0.03%
1/3672
|
0.00%
0/3643
|
|
General disorders
Oedema peripheral
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Vascular disorders
Orthostatic hypotension
|
0.05%
2/3672
|
0.00%
0/3643
|
|
Gastrointestinal disorders
Pancreatitis acute
|
0.03%
1/3672
|
0.03%
1/3643
|
|
Gastrointestinal disorders
Pancreatitis chronic
|
0.03%
1/3672
|
0.03%
1/3643
|
|
Gastrointestinal disorders
Periproctitis
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Nervous system disorders
Polyneuropathy
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Infections and infestations
Postoperative wound infection
|
0.05%
2/3672
|
0.14%
5/3643
|
|
Injury, poisoning and procedural complications
Procedural pain
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Injury, poisoning and procedural complications
Pubis fracture
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.08%
3/3672
|
0.16%
6/3643
|
|
Skin and subcutaneous tissue disorders
Rash pruritic
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Renal and urinary disorders
Renal failure acute
|
0.46%
17/3672
|
0.27%
10/3643
|
|
Infections and infestations
Respiratory tract infection
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Musculoskeletal and connective tissue disorders
Rotator cuff syndrome
|
0.03%
1/3672
|
0.03%
1/3643
|
|
Injury, poisoning and procedural complications
Skin injury
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Gastrointestinal disorders
Subileus
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Vascular disorders
Thrombosis
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Injury, poisoning and procedural complications
Tibia fracture
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Nervous system disorders
Tremor
|
0.03%
1/3672
|
0.03%
1/3643
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour haemorrhage
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Infections and infestations
Urinary tract infection
|
0.22%
8/3672
|
0.25%
9/3643
|
|
Reproductive system and breast disorders
Vaginal haemorrhage
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Cardiac disorders
Ventricular asystole
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Cardiac disorders
Ventricular tachycardia
|
0.22%
8/3672
|
0.30%
11/3643
|
|
Vascular disorders
Accelerated hypertension
|
0.00%
0/3672
|
0.05%
2/3643
|
|
Cardiac disorders
Acute coronary syndrome
|
0.03%
1/3672
|
0.03%
1/3643
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Anal cancer stage IV
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Injury, poisoning and procedural complications
Ankle fracture
|
0.08%
3/3672
|
0.00%
0/3643
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/3672
|
0.05%
2/3643
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/3672
|
0.05%
2/3643
|
|
Infections and infestations
Bacteraemia
|
0.03%
1/3672
|
0.03%
1/3643
|
|
Nervous system disorders
Basilar migraine
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Cardiac disorders
Cardiopulmonary failure
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Infections and infestations
Cholecystitis infective
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.08%
3/3672
|
0.08%
3/3643
|
|
Musculoskeletal and connective tissue disorders
Connective tissue disorder
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Cardiac disorders
Coronary artery insufficiency
|
0.03%
1/3672
|
0.03%
1/3643
|
|
Cardiac disorders
Coronary artery occlusion
|
0.08%
3/3672
|
0.11%
4/3643
|
|
Cardiac disorders
Coronary artery stenosis
|
0.54%
20/3672
|
0.44%
16/3643
|
|
Infections and infestations
Diverticulitis
|
0.00%
0/3672
|
0.03%
1/3643
|
|
General disorders
Drug withdrawal syndrome
|
0.03%
1/3672
|
0.03%
1/3643
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Blood and lymphatic system disorders
Eosinophilia
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Metabolism and nutrition disorders
Failure to thrive
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Gastrointestinal disorders
Gastroduodenitis
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
1.9%
69/3672
|
0.63%
23/3643
|
|
Musculoskeletal and connective tissue disorders
Haemarthrosis
|
0.05%
2/3672
|
0.00%
0/3643
|
|
Respiratory, thoracic and mediastinal disorders
Haemothorax
|
0.08%
3/3672
|
0.00%
0/3643
|
|
Vascular disorders
Hypertensive crisis
|
0.14%
5/3672
|
0.11%
4/3643
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.14%
5/3672
|
0.22%
8/3643
|
|
Vascular disorders
Hypotension
|
0.14%
5/3672
|
0.08%
3/3643
|
|
Cardiac disorders
Ischaemic cardiomyopathy
|
0.03%
1/3672
|
0.08%
3/3643
|
|
Gastrointestinal disorders
Ischaemic gastritis
|
0.00%
0/3672
|
0.03%
1/3643
|
|
General disorders
Ischaemic ulcer
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Cardiac disorders
Left ventricular failure
|
0.03%
1/3672
|
0.08%
3/3643
|
|
Vascular disorders
Leriche syndrome
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Blood and lymphatic system disorders
Leukocytosis
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.16%
6/3672
|
0.11%
4/3643
|
|
Renal and urinary disorders
Nephrolithiasis
|
0.05%
2/3672
|
0.03%
1/3643
|
|
General disorders
Non-cardiac chest pain
|
1.0%
38/3672
|
1.3%
46/3643
|
|
Gastrointestinal disorders
Pharyngoesophageal diverticulum
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pituitary tumour benign
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Injury, poisoning and procedural complications
Postoperative thoracic procedure complication
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Psychiatric disorders
Psychotic disorder
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory distress
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.05%
2/3672
|
0.08%
3/3643
|
|
Infections and infestations
Respiratory tract infection viral
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Infections and infestations
Sepsis
|
0.14%
5/3672
|
0.19%
7/3643
|
|
Injury, poisoning and procedural complications
Silicosis
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Nervous system disorders
Spinal cord haemorrhage
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Infections and infestations
Staphylococcal infection
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Musculoskeletal and connective tissue disorders
Tenosynovitis
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Injury, poisoning and procedural complications
Therapeutic agent toxicity
|
0.03%
1/3672
|
0.03%
1/3643
|
|
Vascular disorders
Thrombophlebitis
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Skin and subcutaneous tissue disorders
Toxic skin eruption
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Ear and labyrinth disorders
Vertigo
|
0.05%
2/3672
|
0.11%
4/3643
|
|
Vascular disorders
Arterial thrombosis
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Vascular disorders
Arteriosclerosis
|
0.05%
2/3672
|
0.00%
0/3643
|
|
Vascular disorders
Artery dissection
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Gastrointestinal disorders
Ascites
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Cardiac disorders
Atrioventricular block second degree
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Hepatobiliary disorders
Bile duct stone
|
0.03%
1/3672
|
0.03%
1/3643
|
|
Renal and urinary disorders
Bladder diverticulum
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Cardiac disorders
Cardiac failure
|
2.6%
94/3672
|
2.3%
82/3643
|
|
Cardiac disorders
Cardio-respiratory arrest
|
0.03%
1/3672
|
0.08%
3/3643
|
|
Infections and infestations
Chronic sinusitis
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Gastrointestinal disorders
Diabetic gastroparesis
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Cardiac disorders
Dressler's syndrome
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Gastrointestinal disorders
Duodenitis
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Renal and urinary disorders
Dysuria
|
0.05%
2/3672
|
0.00%
0/3643
|
|
Nervous system disorders
Encephalopathy
|
0.05%
2/3672
|
0.00%
0/3643
|
|
Infections and infestations
Endocarditis
|
0.03%
1/3672
|
0.05%
2/3643
|
|
Eye disorders
Eye haemorrhage
|
0.05%
2/3672
|
0.00%
0/3643
|
|
General disorders
Fatigue
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Vascular disorders
Femoral arterial stenosis
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Gastrointestinal disorders
Gastric ulcer
|
0.11%
4/3672
|
0.05%
2/3643
|
|
Gastrointestinal disorders
Gastritis erosive
|
0.03%
1/3672
|
0.03%
1/3643
|
|
Gastrointestinal disorders
Gastroduodenal ulcer
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastrointestinal carcinoma
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Gastrointestinal disorders
Haematochezia
|
0.03%
1/3672
|
0.05%
2/3643
|
|
Blood and lymphatic system disorders
Haemorrhagic anaemia
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Gastrointestinal disorders
Haemorrhoids
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.05%
2/3672
|
0.11%
4/3643
|
|
Injury, poisoning and procedural complications
Incisional hernia, obstructive
|
0.05%
2/3672
|
0.00%
0/3643
|
|
Infections and infestations
Infective exacerbation of chronic obstructive airways disease
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Infections and infestations
Intervertebral discitis
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Respiratory, thoracic and mediastinal disorders
Lung disorder
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Eye disorders
Maculopathy
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Psychiatric disorders
Mental status changes
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to liver
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Gastrointestinal disorders
Mouth haemorrhage
|
0.08%
3/3672
|
0.00%
0/3643
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Cardiac disorders
Myocardial ischaemia
|
0.03%
1/3672
|
0.11%
4/3643
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.00%
0/3672
|
0.05%
2/3643
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Oesophageal adenocarcinoma
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Infections and infestations
Osteomyelitis
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pancreatic carcinoma
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Gastrointestinal disorders
Pancreatitis
|
0.05%
2/3672
|
0.03%
1/3643
|
|
Vascular disorders
Peripheral vascular disorder
|
0.03%
1/3672
|
0.25%
9/3643
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.11%
4/3672
|
0.16%
6/3643
|
|
Respiratory, thoracic and mediastinal disorders
Pneumomediastinum
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer
|
0.03%
1/3672
|
0.05%
2/3643
|
|
Reproductive system and breast disorders
Prostatomegaly
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Renal and urinary disorders
Renal injury
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Eye disorders
Retinal detachment
|
0.03%
1/3672
|
0.03%
1/3643
|
|
Gastrointestinal disorders
Retroperitoneal haemorrhage
|
0.05%
2/3672
|
0.05%
2/3643
|
|
Injury, poisoning and procedural complications
Rib fracture
|
0.00%
0/3672
|
0.11%
4/3643
|
|
Cardiac disorders
Sick sinus syndrome
|
0.00%
0/3672
|
0.08%
3/3643
|
|
Cardiac disorders
Sinus bradycardia
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Psychiatric disorders
Suicide attempt
|
0.03%
1/3672
|
0.00%
0/3643
|
|
General disorders
Vessel puncture site haemorrhage
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Investigations
Weight decreased
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Gastrointestinal disorders
Abdominal pain
|
0.14%
5/3672
|
0.05%
2/3643
|
|
Blood and lymphatic system disorders
Anaemia
|
0.44%
16/3672
|
0.22%
8/3643
|
|
Injury, poisoning and procedural complications
Animal bite
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Vascular disorders
Aortic aneurysm
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Cardiac disorders
Aortic valve incompetence
|
0.05%
2/3672
|
0.00%
0/3643
|
|
Infections and infestations
Appendicitis
|
0.11%
4/3672
|
0.00%
0/3643
|
|
Cardiac disorders
Arrhythmia
|
0.11%
4/3672
|
0.03%
1/3643
|
|
Vascular disorders
Arterial stenosis
|
0.03%
1/3672
|
0.00%
0/3643
|
|
General disorders
Asthenia
|
0.00%
0/3672
|
0.16%
6/3643
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
0.03%
1/3672
|
0.05%
2/3643
|
|
Cardiac disorders
Atrioventricular block complete
|
0.00%
0/3672
|
0.14%
5/3643
|
|
Hepatobiliary disorders
Biliary colic
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Respiratory, thoracic and mediastinal disorders
Bronchospasm
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Renal and urinary disorders
Calculus bladder
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Cardiac disorders
Cardiogenic shock
|
0.05%
2/3672
|
0.19%
7/3643
|
|
Gastrointestinal disorders
Colonic polyp
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Injury, poisoning and procedural complications
Coronary artery restenosis
|
0.05%
2/3672
|
0.03%
1/3643
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Metabolism and nutrition disorders
Diabetic foot
|
0.05%
2/3672
|
0.00%
0/3643
|
|
Infections and infestations
Epiglottitis
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Injury, poisoning and procedural complications
Extradural haematoma
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Gastrointestinal disorders
Faeces discoloured
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Injury, poisoning and procedural complications
Fat embolism
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Vascular disorders
Femoral artery occlusion
|
0.05%
2/3672
|
0.00%
0/3643
|
|
Gastrointestinal disorders
Gastritis
|
0.33%
12/3672
|
0.16%
6/3643
|
|
Nervous system disorders
Guillain-Barre syndrome
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Gastrointestinal disorders
Haematemesis
|
0.14%
5/3672
|
0.11%
4/3643
|
|
Metabolism and nutrition disorders
Hypervolaemia
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.08%
3/3672
|
0.00%
0/3643
|
|
Vascular disorders
Intermittent claudication
|
0.03%
1/3672
|
0.08%
3/3643
|
|
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Gastrointestinal disorders
Intestinal haemorrhage
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Respiratory, thoracic and mediastinal disorders
Laryngeal hypertrophy
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lip neoplasm malignant stage unspecified
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Infections and infestations
Lower respiratory tract infection
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Psychiatric disorders
Major depression
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Injury, poisoning and procedural complications
Multiple fractures
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/3672
|
0.05%
2/3643
|
|
Musculoskeletal and connective tissue disorders
Periarthritis
|
0.03%
1/3672
|
0.03%
1/3643
|
|
Vascular disorders
Peripheral embolism
|
0.00%
0/3672
|
0.05%
2/3643
|
|
Injury, poisoning and procedural complications
Post procedural haemorrhage
|
0.05%
2/3672
|
0.00%
0/3643
|
|
Cardiac disorders
Prinzmetal angina
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Infections and infestations
Pulmonary tuberculosis
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Gastrointestinal disorders
Rectal fissure
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Renal and urinary disorders
Renal failure
|
0.22%
8/3672
|
0.14%
5/3643
|
|
Renal and urinary disorders
Renal infarct
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Musculoskeletal and connective tissue disorders
Rheumatoid arthritis
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Infections and infestations
Septic shock
|
0.11%
4/3672
|
0.05%
2/3643
|
|
Skin and subcutaneous tissue disorders
Skin necrosis
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Small cell lung cancer stage unspecified
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Nervous system disorders
Spinal cord ischaemia
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Cardiac disorders
Tachycardia
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Nervous system disorders
VIIth nerve paralysis
|
0.05%
2/3672
|
0.00%
0/3643
|
|
Cardiac disorders
Ventricular fibrillation
|
0.22%
8/3672
|
0.14%
5/3643
|
|
Infections and infestations
Wound infection
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Injury, poisoning and procedural complications
Wound secretion
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Infections and infestations
Abscess limb
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Cardiac disorders
Acute left ventricular failure
|
0.03%
1/3672
|
0.03%
1/3643
|
|
Psychiatric disorders
Alcohol withdrawal syndrome
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Musculoskeletal and connective tissue disorders
Arthropathy
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Cardiac disorders
Atrial fibrillation
|
0.71%
26/3672
|
0.80%
29/3643
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.05%
2/3672
|
0.19%
7/3643
|
|
Injury, poisoning and procedural complications
Brain contusion
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Cardiac disorders
Cardiac disorder
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Cardiac disorders
Cardiac perforation
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Cardiac disorders
Cardiac tamponade
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Nervous system disorders
Carotid artery stenosis
|
0.14%
5/3672
|
0.05%
2/3643
|
|
Investigations
Clostridium test positive
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Psychiatric disorders
Confusional state
|
0.00%
0/3672
|
0.05%
2/3643
|
|
Cardiac disorders
Congestive cardiomyopathy
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Immune system disorders
Contrast media allergy
|
0.03%
1/3672
|
0.00%
0/3643
|
|
General disorders
Death
|
0.30%
11/3672
|
0.22%
8/3643
|
|
General disorders
Device dislocation
|
0.03%
1/3672
|
0.08%
3/3643
|
|
Infections and infestations
Device related sepsis
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Metabolism and nutrition disorders
Diabetic ketoacidosis
|
0.11%
4/3672
|
0.05%
2/3643
|
|
Gastrointestinal disorders
Diverticulum
|
0.05%
2/3672
|
0.03%
1/3643
|
|
Nervous system disorders
Dizziness
|
0.11%
4/3672
|
0.16%
6/3643
|
|
Metabolism and nutrition disorders
Electrolyte imbalance
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Infections and infestations
Encephalitis herpes
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Injury, poisoning and procedural complications
Femoral neck fracture
|
0.00%
0/3672
|
0.05%
2/3643
|
|
Injury, poisoning and procedural complications
Femur fracture
|
0.05%
2/3672
|
0.05%
2/3643
|
|
Injury, poisoning and procedural complications
Foot fracture
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Gastrointestinal disorders
Gastric polyps
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Infections and infestations
Gastroenteritis
|
0.08%
3/3672
|
0.14%
5/3643
|
|
Infections and infestations
Gastrointestinal infection
|
0.05%
2/3672
|
0.00%
0/3643
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Glioblastoma
|
0.03%
1/3672
|
0.03%
1/3643
|
|
Renal and urinary disorders
Haematuria
|
0.35%
13/3672
|
0.14%
5/3643
|
|
Investigations
Haemoglobin decreased
|
0.11%
4/3672
|
0.00%
0/3643
|
|
Injury, poisoning and procedural complications
Head injury
|
0.00%
0/3672
|
0.05%
2/3643
|
|
Hepatobiliary disorders
Hepatic failure
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Hepatobiliary disorders
Hepatic function abnormal
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Hepatobiliary disorders
Hepatitis acute
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Metabolism and nutrition disorders
Hyperglycaemic hyperosmolar nonketotic syndrome
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Endocrine disorders
Hyperthyroidism
|
0.05%
2/3672
|
0.00%
0/3643
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.05%
2/3672
|
0.08%
3/3643
|
|
Injury, poisoning and procedural complications
Incisional hernia
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Infections and infestations
Injection site infection
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Gastrointestinal disorders
Intestinal obstruction
|
0.03%
1/3672
|
0.03%
1/3643
|
|
Metabolism and nutrition disorders
Iron deficiency
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Vascular disorders
Ischaemia
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Injury, poisoning and procedural complications
Joint injury
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Infections and infestations
Laryngitis
|
0.00%
0/3672
|
0.05%
2/3643
|
|
Cardiac disorders
Mitral valve incompetence
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Cardiac disorders
Myocardial infarction
|
4.1%
150/3672
|
4.3%
158/3643
|
|
Blood and lymphatic system disorders
Nephrogenic anaemia
|
0.00%
0/3672
|
0.05%
2/3643
|
|
Investigations
Occult blood positive
|
0.05%
2/3672
|
0.00%
0/3643
|
|
Cardiac disorders
Parasystole
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Cardiac disorders
Pericarditis
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Vascular disorders
Peripheral artery aneurysm
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Nervous system disorders
Presyncope
|
0.05%
2/3672
|
0.08%
3/3643
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary congestion
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
|
0.25%
9/3672
|
0.08%
3/3643
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal cell carcinoma
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Cardiac disorders
Sinus tachycardia
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Infections and infestations
Skin infection
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Injury, poisoning and procedural complications
Soft tissue injury
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Testis cancer recurrent
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Cardiac disorders
Ventricle rupture
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Ear and labyrinth disorders
Vertigo positional
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Gastrointestinal disorders
Abdominal hernia
|
0.03%
1/3672
|
0.03%
1/3643
|
|
Injury, poisoning and procedural complications
Accidental overdose
|
0.14%
5/3672
|
0.05%
2/3643
|
|
Renal and urinary disorders
Acute prerenal failure
|
0.05%
2/3672
|
0.00%
0/3643
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/3672
|
0.05%
2/3643
|
|
Cardiac disorders
Angina unstable
|
4.3%
157/3672
|
4.3%
157/3643
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder cancer
|
0.05%
2/3672
|
0.00%
0/3643
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bowen's disease
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Infections and infestations
Bronchitis
|
0.16%
6/3672
|
0.03%
1/3643
|
|
Infections and infestations
Bronchopneumonia
|
0.00%
0/3672
|
0.05%
2/3643
|
|
Musculoskeletal and connective tissue disorders
Bursitis
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Nervous system disorders
Carotid artery occlusion
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Injury, poisoning and procedural complications
Chest injury
|
0.03%
1/3672
|
0.00%
0/3643
|
|
General disorders
Chest pain
|
0.30%
11/3672
|
0.19%
7/3643
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.38%
14/3672
|
0.22%
8/3643
|
|
Psychiatric disorders
Completed suicide
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Gastrointestinal disorders
Constipation
|
0.03%
1/3672
|
0.03%
1/3643
|
|
Injury, poisoning and procedural complications
Contusion
|
0.16%
6/3672
|
0.08%
3/3643
|
|
Cardiac disorders
Coronary artery dissection
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Vascular disorders
Deep vein thrombosis
|
0.08%
3/3672
|
0.03%
1/3643
|
|
Psychiatric disorders
Depression
|
0.00%
0/3672
|
0.11%
4/3643
|
|
Skin and subcutaneous tissue disorders
Dermatitis
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Gastrointestinal disorders
Diarrhoea
|
0.03%
1/3672
|
0.03%
1/3643
|
|
Immune system disorders
Drug hypersensitivity
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Injury, poisoning and procedural complications
Drug toxicity
|
0.00%
0/3672
|
0.05%
2/3643
|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Endometrial cancer
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Injury, poisoning and procedural complications
Facial bones fracture
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Vascular disorders
Femoral artery aneurysm
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Metabolism and nutrition disorders
Fluid retention
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Infections and infestations
Gallbladder empyema
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
0.05%
2/3672
|
0.03%
1/3643
|
|
Investigations
Haematocrit decreased
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Vascular disorders
Haematoma
|
0.38%
14/3672
|
0.14%
5/3643
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
0.05%
2/3672
|
0.05%
2/3643
|
|
Vascular disorders
Haemorrhage
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Nervous system disorders
Haemorrhage intracranial
|
0.22%
8/3672
|
0.03%
1/3643
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Investigations
Liver function test abnormal
|
0.03%
1/3672
|
0.03%
1/3643
|
|
Infections and infestations
Lobar pneumonia
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Infections and infestations
Localised infection
|
0.00%
0/3672
|
0.08%
3/3643
|
|
Blood and lymphatic system disorders
Lymphadenopathy
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Gastrointestinal disorders
Mechanical ileus
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Gastrointestinal disorders
Melaena
|
0.11%
4/3672
|
0.03%
1/3643
|
|
Infections and infestations
Necrotising fasciitis
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Non-small cell lung cancer stage I
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Injury, poisoning and procedural complications
Operative haemorrhage
|
0.03%
1/3672
|
0.03%
1/3643
|
|
General disorders
Pain
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.08%
3/3672
|
0.00%
0/3643
|
|
Psychiatric disorders
Panic disorder
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Cardiac disorders
Pericardial effusion
|
0.11%
4/3672
|
0.00%
0/3643
|
|
Cardiac disorders
Pericardial haemorrhage
|
0.08%
3/3672
|
0.11%
4/3643
|
|
Gastrointestinal disorders
Periodontitis
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary artery thrombosis
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Infections and infestations
Pyelonephritis
|
0.05%
2/3672
|
0.03%
1/3643
|
|
General disorders
Pyrexia
|
0.08%
3/3672
|
0.03%
1/3643
|
|
Injury, poisoning and procedural complications
Radius fracture
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Infections and infestations
Rectal abscess
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Renal and urinary disorders
Renal impairment
|
0.14%
5/3672
|
0.16%
6/3643
|
|
Skin and subcutaneous tissue disorders
Skin ulcer
|
0.05%
2/3672
|
0.00%
0/3643
|
|
Infections and infestations
Soft tissue infection
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Musculoskeletal and connective tissue disorders
Spinal osteoarthritis
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Infections and infestations
Staphylococcal bacteraemia
|
0.05%
2/3672
|
0.00%
0/3643
|
|
General disorders
Sudden cardiac death
|
0.27%
10/3672
|
0.30%
11/3643
|
|
Nervous system disorders
Syncope
|
0.35%
13/3672
|
0.38%
14/3643
|
|
Infections and infestations
Tracheobronchitis
|
0.03%
1/3672
|
0.03%
1/3643
|
|
Infections and infestations
Urosepsis
|
0.08%
3/3672
|
0.00%
0/3643
|
|
Injury, poisoning and procedural complications
Vascular pseudoaneurysm
|
0.08%
3/3672
|
0.03%
1/3643
|
|
Cardiac disorders
Ventricular arrhythmia
|
0.05%
2/3672
|
0.03%
1/3643
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/3672
|
0.05%
2/3643
|
|
Injury, poisoning and procedural complications
Wound
|
0.03%
1/3672
|
0.03%
1/3643
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.05%
2/3672
|
0.00%
0/3643
|
|
Metabolism and nutrition disorders
Acidosis
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma pancreas
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Nervous system disorders
Altered state of consciousness
|
0.05%
2/3672
|
0.00%
0/3643
|
|
Injury, poisoning and procedural complications
Arterial injury
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Vascular disorders
Arterial thrombosis limb
|
0.03%
1/3672
|
0.03%
1/3643
|
|
Cardiac disorders
Arteriosclerosis coronary artery
|
0.16%
6/3672
|
0.08%
3/3643
|
|
Infections and infestations
Bacterial sepsis
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Reproductive system and breast disorders
Balanoposthitis
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder cancer stage II
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Investigations
Blood creatinine increased
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Cardiac disorders
Bradycardia
|
0.25%
9/3672
|
0.08%
3/3643
|
|
Respiratory, thoracic and mediastinal disorders
Bronchial disorder
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Cardiac disorders
Cardiovascular insufficiency
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Nervous system disorders
Carotid arteriosclerosis
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Hepatobiliary disorders
Cholecystitis
|
0.16%
6/3672
|
0.08%
3/3643
|
|
Hepatobiliary disorders
Cholestasis
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Vascular disorders
Circulatory collapse
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Gastrointestinal disorders
Colitis
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer
|
0.08%
3/3672
|
0.11%
4/3643
|
|
Nervous system disorders
Convulsion
|
0.05%
2/3672
|
0.00%
0/3643
|
|
Cardiac disorders
Coronary artery disease
|
0.60%
22/3672
|
0.49%
18/3643
|
|
Metabolism and nutrition disorders
Dehydration
|
0.11%
4/3672
|
0.11%
4/3643
|
|
Nervous system disorders
Dementia
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Skin and subcutaneous tissue disorders
Dermatomyositis
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Metabolism and nutrition disorders
Diabetes mellitus inadequate control
|
0.03%
1/3672
|
0.05%
2/3643
|
|
Nervous system disorders
Diabetic neuropathy
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Investigations
Drug screen positive
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Gastrointestinal disorders
Duodenal ulcer perforation
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Investigations
Electrocardiogram QT prolonged
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.14%
5/3672
|
0.14%
5/3643
|
|
Infections and infestations
Fungal skin infection
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Gastrointestinal disorders
Gastric varices haemorrhage
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Renal and urinary disorders
Hydronephrosis
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Vascular disorders
Hypertensive emergency
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Gastrointestinal disorders
Ileus
|
0.05%
2/3672
|
0.00%
0/3643
|
|
Injury, poisoning and procedural complications
In-stent coronary artery restenosis
|
0.19%
7/3672
|
0.19%
7/3643
|
|
Infections and infestations
Infected bites
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Gastrointestinal disorders
Inguinal hernia
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Nervous system disorders
Intercostal neuralgia
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Gastrointestinal disorders
Intestinal ischaemia
|
0.05%
2/3672
|
0.00%
0/3643
|
|
Cardiac disorders
Intracardiac thrombus
|
0.00%
0/3672
|
0.05%
2/3643
|
|
Nervous system disorders
Intraventricular haemorrhage
|
0.14%
5/3672
|
0.00%
0/3643
|
|
Cardiac disorders
Left ventricular dysfunction
|
0.05%
2/3672
|
0.03%
1/3643
|
|
Musculoskeletal and connective tissue disorders
Lumbar spinal stenosis
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignant
|
0.14%
5/3672
|
0.03%
1/3643
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lymphoma
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Nervous system disorders
Mental retardation
|
0.00%
0/3672
|
0.03%
1/3643
|
|
General disorders
Multi-organ failure
|
0.11%
4/3672
|
0.03%
1/3643
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
0.03%
1/3672
|
0.11%
4/3643
|
|
Cardiac disorders
Myocardial rupture
|
0.03%
1/3672
|
0.03%
1/3643
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm malignant
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Renal and urinary disorders
Nephropathy
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Renal and urinary disorders
Nephropathy toxic
|
0.08%
3/3672
|
0.00%
0/3643
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.00%
0/3672
|
0.08%
3/3643
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pancreatic carcinoma metastatic
|
0.05%
2/3672
|
0.00%
0/3643
|
|
Nervous system disorders
Paraplegia
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Injury, poisoning and procedural complications
Patella fracture
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Vascular disorders
Peripheral arterial occlusive disease
|
0.11%
4/3672
|
0.11%
4/3643
|
|
Respiratory, thoracic and mediastinal disorders
Pleuritic pain
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Gastrointestinal disorders
Reflux oesophagitis
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Renal and urinary disorders
Renal colic
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Renal and urinary disorders
Renal failure chronic
|
0.08%
3/3672
|
0.05%
2/3643
|
|
Nervous system disorders
Sciatica
|
0.05%
2/3672
|
0.00%
0/3643
|
|
Cardiac disorders
Sinus arrhythmia
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Infections and infestations
Sinusitis
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Musculoskeletal and connective tissue disorders
Spinal column stenosis
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Spinal meningioma benign
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma of skin
|
0.03%
1/3672
|
0.03%
1/3643
|
|
Nervous system disorders
Subarachnoid haemorrhage
|
0.05%
2/3672
|
0.05%
2/3643
|
|
Infections and infestations
Subcutaneous abscess
|
0.03%
1/3672
|
0.00%
0/3643
|
|
Renal and urinary disorders
Urethral stenosis
|
0.00%
0/3672
|
0.03%
1/3643
|
|
Cardiac disorders
Ventricular extrasystoles
|
0.03%
1/3672
|
0.00%
0/3643
|
Other adverse events
| Measure |
Apixaban 5 mg BID
n=3672 participants at risk
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 BID
n=3643 participants at risk
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.
|
|---|---|---|
|
General disorders
Chest pain
|
5.1%
186/3672
|
4.7%
173/3643
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
5.1%
186/3672
|
1.7%
63/3643
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER