Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Evaluation of Dual Therapy With Dabigatran vs. Triple Therapy With Warfarin in Patients With AF That Undergo a PCI With Stenting (REDUAL-PCI)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02164864
Recruitment Status : Completed
First Posted : June 17, 2014
Results First Posted : July 31, 2018
Last Update Posted : July 31, 2018
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Atrial Fibrillation
Percutaneous Coronary Intervention
Interventions Drug: Dabigatran Etexilate 110mg
Drug: Warfarin 3mg
Drug: Aspirin
Drug: Dabigatran Etexilate 150mg
Drug: Clopidogrel or Ticagrelor
Drug: Warfarin 5mg
Drug: Warfarin 1mg
Enrollment 2725
Recruitment Details Patients aged ≥80 years in the United States of America (USA) were assigned to 110 milligram (mg) Dual antithrombotic therapy with dabigatran etexilate (DE-DAT), 150 mg DE-DAT, or warfarin. All other patients including aged ≥80 years (for Japan ≥70 years) outside of the USA were assigned to 110 mg DE-DAT or warfarin
Pre-assignment Details All patients (Pts) were screened for eligibility to participate in trial. Pts attended sites to ensure that they met all implemented inclusion/exclusion criteria. Pts were not to be randomised to trial drug if any of specific entry criteria was violated. In this study, 2725 Pts were entered & randomised. 2678 Pts were treated.
Arm/Group Title Dabigatran Etexilate 110mg Dabigatran Etexilate 150mg Warfarin
Hide Arm/Group Description Patients were orally administered Dabigatran Etexilate 110mg capsule twice daily (BID) for at least 6 months. Patients were orally administered Dabigatran Etexilate 150mg capsule twice daily (BID) for at least 6 months. Patients were orally administered warfarin 1 mg, 3 mg, or 5 mg tablets once daily for at least 6 months. The warfarin dose was titrated as needed to maintain the target International normalised ratio (INR) of 2.0 to 3.0 (2.0 to 2.6 for Japanese patients aged ≥70 years); 2.0 to 2.5 if feasible
Period Title: Overall Study
Started 981 [1] 763 [1] 981 [1]
Completed 886 703 849
Not Completed 95 60 132
Reason Not Completed
Trial disease worsening             7             5             1
Other pre-existing disease worsening             6             4             9
Other Adverse Event (AE)             52             32             49
Protocol Violation             2             4             1
Lost to Follow-up             4             3             2
Consent withdrawn, not due to AE             21             8             56
Other than stated             3             4             14
[1]
Started are the Randomised/entered patients.
Arm/Group Title Dabigatran Etexilate 110mg Dabigatran Etexilate 150mg Warfarin Total
Hide Arm/Group Description Patients were orally administered Dabigatran Etexilate 110mg capsule twice daily (BID) for at least 6 months. Patients were orally administered Dabigatran Etexilate 150mg capsule twice daily (BID) for at least 6 months. Patients were orally administered warfarin 1 mg, 3 mg, or 5 mg tablets once daily for at least 6 months. The warfarin dose was titrated as needed to maintain the target International normalised ratio (INR) of 2.0 to 3.0 (2.0 to 2.6 for Japanese patients aged ≥70 years); 2.0 to 2.5 if feasible Total of all reporting groups
Overall Number of Baseline Participants 981 763 981 2725
Hide Baseline Analysis Population Description
The anaysis set used was Full analysis set (FAS)
Age, Continuous   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 981 participants 763 participants 981 participants 2725 participants
71.5  (8.87) 68.6  (7.65) 71.7  (8.90) 70.8  (8.66)
[1]
Measure Description: Age at the time of signing informed consent form is presented.
[2]
Measure Analysis Population Description: FAS
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 981 participants 763 participants 981 participants 2725 participants
<80: EU/ROW
725
  73.9%
699
  91.6%
718
  73.2%
2142
  78.6%
<80: USA
54
   5.5%
53
   6.9%
61
   6.2%
168
   6.2%
≥80: EU/ROW
189
  19.3%
3
   0.4%
192
  19.6%
384
  14.1%
≥80: USA
13
   1.3%
8
   1.0%
10
   1.0%
31
   1.1%
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 981 participants 763 participants 981 participants 2725 participants
Female
253
  25.8%
171
  22.4%
231
  23.5%
655
  24.0%
Male
728
  74.2%
592
  77.6%
750
  76.5%
2070
  76.0%
[1]
Measure Analysis Population Description: FAS
Ethnicity (NIH/OMB)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 981 participants 763 participants 981 participants 2725 participants
Hispanic or Latino
70
   7.1%
46
   6.0%
59
   6.0%
175
   6.4%
Not Hispanic or Latino
903
  92.0%
700
  91.7%
904
  92.2%
2507
  92.0%
Unknown or Not Reported
8
   0.8%
17
   2.2%
18
   1.8%
43
   1.6%
[1]
Measure Analysis Population Description: FAS
Race/Ethnicity, Customized   [1] [2] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 981 participants 763 participants 981 participants 2725 participants
Asian
116
  11.8%
79
  10.4%
125
  12.7%
320
  11.7%
Black
5
   0.5%
7
   0.9%
3
   0.3%
15
   0.6%
White
851
  86.7%
658
  86.2%
835
  85.1%
2344
  86.0%
Other
5
   0.5%
8
   1.0%
7
   0.7%
20
   0.7%
Missing
4
   0.4%
11
   1.4%
11
   1.1%
26
   1.0%
[1]
Measure Description: The details on Race has been provided
[2]
Measure Analysis Population Description: FAS
1.Primary Outcome
Title Time to First Adjudicated ISTH MBE or CRNMBE
Hide Description

Time to event analysis of patients with first adjudicated International Society of Thrombosis and Haemostasis (ISTH) Major Bleeding Event (MBE) or Clinically Relevant Non Major Bleeding Event (CRNMBE). The number of observed patients with adjudicated ISTH MBE or CRNMBE was reported.

Full analysis set (FAS): All consenting patients randomised were analysed in the treatment group to which they were randomised regardless of whether they took trial medication. The start date of the observation period for this analysis set was the date of randomisation. Patients who discontinued trial medication were followed until the end of the trial.

Patients who were lost to follow-up for vital status were censored for the primary endpoint at the time of their last known vital status.

Intention to treat period: The observation period for these analysis was the so called 'intention to treat period'.

Time Frame up to 30 months
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis set (FAS) following the intention-to-treat principle.
Arm/Group Title Dabigatran Etexilate 110mg Dabigatran Etexilate 150mg Warfarin Warfarin (Excluding Elder Patients Outside USA)
Hide Arm/Group Description:
Patients were orally administered Dabigatran Etexilate 110mg capsule twice daily (BID) for at least 6 months.
Patients were orally administered Dabigatran Etexilate 150mg capsule twice daily (BID) for at least 6 months.
Patients were orally administered warfarin 1 mg, 3 mg, or 5 mg tablets once daily for at least 6 months. The warfarin dose was titrated as needed to maintain the target International normalised ratio (INR) of 2.0 to 3.0 (2.0 to 2.6 for Japanese patients aged ≥70 years); 2.0 to 2.5 if feasible
Patients were orally administered warfarin once daily. The warfarin dose was titrated as needed to maintain the target INR of 2.0 to 3.0 ; 2.0 to 2.5 if feasible. Elderly patients who were outside the USA were excluded.
Overall Number of Participants Analyzed 981 763 981 764
Measure Type: Count of Participants
Unit of Measure: Participants
151
  15.4%
154
  20.2%
264
  26.9%
196
  25.7%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dabigatran Etexilate 110mg, Warfarin
Comments A pre-defined hierarchical testing approach was used. This was the first step in hierarchy. The upper bound of the Wald confidence interval (CI) of the HR of Dabigatran Etexilate 110mg vs Warfarin (one-sided 97.5%) was compared with this noninferiority margin for the testing of non-inferiority.
Type of Statistical Test Non-Inferiority
Comments All non-inferiority tests were based on a margin of 1.38.
Statistical Test of Hypothesis P-Value <0.0001
Comments P values for noninferiority were calculated at a one-sided alpha level of 0.025
Method Regression, Cox
Comments The Cox proportional hazard model is stratified by age, non−elderly vs elderly [<70 or >=70 in Japan and <80 or >=80 years old elsewhere].
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.52
Confidence Interval (2-Sided) 95%
0.42 to 0.63
Estimation Comments Hazard Ratio (HR) and Wald confidence intervals are derived from a Cox proportional-hazard model
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Dabigatran Etexilate 150mg, Warfarin (Excluding Elder Patients Outside USA)
Comments A pre-defined hierarchical testing approach was used. This was the second step in hierarchy. The upper bound of the Wald confidence interval (CI) of the HR of Dabigatran Etexilate 150mg vs Warfarin (one-sided 97.5%) was compared with this noninferiority margin for the testing of non-inferiority
Type of Statistical Test Non-Inferiority
Comments All non-inferiority tests were based on a margin of 1.38.
Statistical Test of Hypothesis P-Value <.0001
Comments P-values for non-inferiority were calculated at a one-sided alpha level of 0.025
Method Regression, Cox
Comments unstratified Cox proportional hazards model was used and elderly patients outside the USA were excluded
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.72
Confidence Interval (2-Sided) 95%
0.58 to 0.88
Estimation Comments Hazard Ratio (HR) and Wald confidence intervals are derived from a Cox proportional-hazard model
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Dabigatran Etexilate 110mg, Warfarin
Comments A pre-defined hierarchical testing approach was used. This was the fourth step in hierarchy.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Wald 2-sided p-value from (stratified) Cox proportional hazards model
Method Regression, Cox
Comments The Cox proportional hazard model is stratified by age, non−elderly vs elderly [<70 or >=70 in Japan and <80 or >=80 years old elsewhere].
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.52
Confidence Interval (2-Sided) 95%
0.42 to 0.63
Estimation Comments Hazard Ratio (HR) and Wald confidence intervals are derived from a Cox proportional-hazard model
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Dabigatran Etexilate 150mg, Warfarin (Excluding Elder Patients Outside USA)
Comments A pre-defined hierarchical testing approach was used. This was the sixth step in hierarchy.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0020
Comments unstratified Cox proportional hazards model was used and elderly patients outside the USA were excluded
Method Regression, Cox
Comments Wald 2-sided p-value from (unstratified) Cox proportional hazards model
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.72
Confidence Interval (2-Sided) 95%
0.58 to 0.88
Estimation Comments [Not Specified]
Other Statistical Analysis Hazard Ratio (HR) and Wald confidence intervals are derived from a Cox proportional-hazard model
2.Secondary Outcome
Title Time to Adjudicated Undetermined Cause of Death
Hide Description

Time to event analysis of patients with adjudicated Undetermined cause of death. The number of observed patients with adjudicated Undetermined cause of death was reported.

This is referred to a death not attributable to cardiovascular (CV) death or to a non-cardiovascular (non-CV) cause. Inability to classify the cause of death may have been due to lack of information (e.g. the only available information was “patient died”) or when there was insufficient supporting information or detail to assign the cause of death.

Time Frame up to 30 months
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis set (FAS) following the intention-to-treat principle.
Arm/Group Title Dabigatran Etexilate 110mg Dabigatran Etexilate 150mg Warfarin Warfarin (Excluding Elder Patients Outside USA)
Hide Arm/Group Description:
Patients were orally administered Dabigatran Etexilate 110mg capsule twice daily (BID) for at least 6 months.
Patients were orally administered Dabigatran Etexilate 150mg capsule twice daily (BID) for at least 6 months.
Patients were orally administered warfarin 1 mg, 3 mg, or 5 mg tablets once daily for at least 6 months. The warfarin dose was titrated as needed to maintain the target International normalised ratio (INR) of 2.0 to 3.0 (2.0 to 2.6 for Japanese patients aged ≥70 years); 2.0 to 2.5 if feasible
Patients were orally administered warfarin once daily. The warfarin dose was titrated as needed to maintain the target INR of 2.0 to 3.0 ; 2.0 to 2.5 if feasible. Elderly patients who were outside the USA were excluded.
Overall Number of Participants Analyzed 981 763 981 764
Measure Type: Count of Participants
Unit of Measure: Participants
4
   0.4%
5
   0.7%
4
   0.4%
3
   0.4%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dabigatran Etexilate 110mg, Warfarin
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9862
Comments Wald 2-sided p-value from (stratified) Cox proportional hazards model
Method Regression, Cox
Comments The Cox proportional hazard model is stratified by age, non−elderly vs elderly [<70 or >=70 in Japan and <80 or >=80 years old elsewhere].
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.99
Confidence Interval (2-Sided) 95%
0.25 to 3.95
Estimation Comments Hazard Ratio (HR) and Wald confidence intervals are derived from a Cox proportional-hazard model
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Dabigatran Etexilate 150mg, Warfarin (Excluding Elder Patients Outside USA)
Comments [Not Specified]
Type of Statistical Test Other
Comments Wald 2-sided p-value from (unstratified) Cox proportional hazards model
Statistical Test of Hypothesis P-Value 0.5277
Comments [Not Specified]
Method Regression, Cox
Comments unstratified Cox proportional hazards model was used and elderly patients outside the USA were excluded from
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.59
Confidence Interval (2-Sided) 95%
0.38 to 6.64
Estimation Comments Hazard Ratio (HR) and Wald confidence intervals are derived from a Cox proportional-hazard model
3.Secondary Outcome
Title Time to Adjudicated Non-CV
Hide Description

Time to event analysis of patients with adjudicated Non-cardiovascular (Non-CV). The number of observed patients with adjudicated Non-CV was reported.

Non-CV death was defined as any death with a specific cause that was not thought to be CV. These were possible examples of non-CV causes of death: Pulmonary, Renal, Gastrointestinal, Hepatobiliary, Pancreatic Infection(included sepsis), Inflammatory (e.g. systemic inflammatory response syndrome) or immune (including autoimmune), Haemorrhage that was neither CV bleeding nor a stroke, Non-CV procedure or surgery, Trauma, Suicide, Non-prescription drug reaction or overdose, Prescription drug reaction or overdose, Neurological (non-CV), Malignancy, Other non-CV

Time Frame up to 30 months
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis set (FAS) following the intention-to-treat principle.
Arm/Group Title Dabigatran Etexilate 110mg Dabigatran Etexilate 150mg Warfarin Warfarin (Excluding Elder Patients Outside USA)
Hide Arm/Group Description:
Patients were orally administered Dabigatran Etexilate 110mg capsule twice daily (BID) for at least 6 months.
Patients were orally administered Dabigatran Etexilate 150mg capsule twice daily (BID) for at least 6 months.
Patients were orally administered warfarin 1 mg, 3 mg, or 5 mg tablets once daily for at least 6 months. The warfarin dose was titrated as needed to maintain the target International normalised ratio (INR) of 2.0 to 3.0 (2.0 to 2.6 for Japanese patients aged ≥70 years); 2.0 to 2.5 if feasible
Patients were orally administered warfarin once daily. The warfarin dose was titrated as needed to maintain the target INR of 2.0 to 3.0 ; 2.0 to 2.5 if feasible. Elderly patients who were outside the USA were excluded.
Overall Number of Participants Analyzed 981 763 981 764
Measure Type: Count of Participants
Unit of Measure: Participants
14
   1.4%
4
   0.5%
13
   1.3%
8
   1.0%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dabigatran Etexilate 110mg, Warfarin
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8853
Comments Wald 2-sided p-value from (stratified) Cox proportional hazards model
Method Regression, Cox
Comments The Cox proportional hazard model is stratified by age, non−elderly vs elderly [<70 or >=70 in Japan and <80 or >=80 years old elsewhere].
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.06
Confidence Interval (2-Sided) 95%
0.50 to 2.25
Estimation Comments Hazard Ratio (HR) and Wald confidence intervals are derived from a Cox proportional-hazard model
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Dabigatran Etexilate 150mg, Warfarin (Excluding Elder Patients Outside USA)
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2380
Comments Wald 2-sided p-value from (unstratified) Cox proportional hazards model
Method Regression, Cox
Comments unstratified Cox proportional hazards model was used and elderly patients outside the USA were excluded from
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.49
Confidence Interval (2-Sided) 95%
0.15 to 1.61
Estimation Comments Hazard Ratio (HR) and Wald confidence intervals are derived from a Cox proportional-hazard model
4.Secondary Outcome
Title Time to Adjudicated CV
Hide Description

Time to event analysis of patients with adjudicated Cardiovascular (CV) death. The number of observed patients with adjudicated Cardiovascular (CV) death was reported.

CV death included death resulting from an acute myocardial infarction, sudden cardiac death, death due to heart failure, death due to stroke, death due to CV procedures, death due to CV haemorrhage, and death due to other CV causes.

Time Frame up to 30 months
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis set (FAS) following the intention-to-treat principle.
Arm/Group Title Dabigatran Etexilate 110mg Dabigatran Etexilate 150mg Warfarin Warfarin (Excluding Elder Patients Outside USA)
Hide Arm/Group Description:
Patients were orally administered Dabigatran Etexilate 110mg capsule twice daily (BID) for at least 6 months.
Patients were orally administered Dabigatran Etexilate 150mg capsule twice daily (BID) for at least 6 months.
Patients were orally administered warfarin 1 mg, 3 mg, or 5 mg tablets once daily for at least 6 months. The warfarin dose was titrated as needed to maintain the target International normalised ratio (INR) of 2.0 to 3.0 (2.0 to 2.6 for Japanese patients aged ≥70 years); 2.0 to 2.5 if feasible
Patients were orally administered warfarin once daily. The warfarin dose was titrated as needed to maintain the target INR of 2.0 to 3.0 ; 2.0 to 2.5 if feasible. Elderly patients who were outside the USA were excluded.
Overall Number of Participants Analyzed 981 763 981 764
Measure Type: Count of Participants
Unit of Measure: Participants
37
   3.8%
21
   2.8%
31
   3.2%
24
   3.1%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dabigatran Etexilate 110mg, Warfarin
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5252
Comments Wald 2-sided p-value from (stratified) Cox proportional hazards model
Method Regression, Cox
Comments The Cox proportional hazard model is stratified by age, non−elderly vs elderly [<70 or >=70 in Japan and <80 or >=80 years old elsewhere].
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.17
Confidence Interval (2-Sided) 95%
0.72 to 1.88
Estimation Comments Hazard Ratio (HR) and Wald confidence intervals are derived from a Cox proportional-hazard model
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Dabigatran Etexilate 150mg, Warfarin (Excluding Elder Patients Outside USA)
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5670
Comments Wald 2-sided p-value from (unstratified) Cox proportional hazards model
Method Regression, Cox
Comments unstratified Cox proportional hazards model was used and elderly patients outside the USA were excluded from
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.84
Confidence Interval (2-Sided) 95%
0.47 to 1.51
Estimation Comments Hazard Ratio (HR) and Wald confidence intervals are derived from a Cox proportional-hazard model
5.Secondary Outcome
Title Time to Adjudicated All Cause Death
Hide Description Time to event analysis of patients with adjudicated all cause death. The number of observed patients with adjudicated all cause death was reported. All cause death is defined as the death from any cause included CV death, non-CV death, and undetermined cause of death.
Time Frame up to 30 months
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis set (FAS) following the intention-to-treat principle.
Arm/Group Title Dabigatran Etexilate 110mg Dabigatran Etexilate 150mg Warfarin Warfarin (Excluding Elder Patients Outside USA)
Hide Arm/Group Description:
Patients were orally administered Dabigatran Etexilate 110mg capsule twice daily (BID) for at least 6 months.
Patients were orally administered Dabigatran Etexilate 150mg capsule twice daily (BID) for at least 6 months.
Patients were orally administered warfarin 1 mg, 3 mg, or 5 mg tablets once daily for at least 6 months. The warfarin dose was titrated as needed to maintain the target International normalised ratio (INR) of 2.0 to 3.0 (2.0 to 2.6 for Japanese patients aged ≥70 years); 2.0 to 2.5 if feasible
Patients were orally administered warfarin once daily. The warfarin dose was titrated as needed to maintain the target INR of 2.0 to 3.0 ; 2.0 to 2.5 if feasible. Elderly patients who were outside the USA were excluded.
Overall Number of Participants Analyzed 981 763 981 764
Measure Type: Count of Participants
Unit of Measure: Participants
55
   5.6%
30
   3.9%
48
   4.9%
35
   4.6%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dabigatran Etexilate 110mg, Warfarin
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5579
Comments Wald 2-sided p-value from (stratified) Cox proportional hazards model
Method Regression, Cox
Comments The Cox proportional hazard model is stratified by age, non−elderly vs elderly [<70 or >=70 in Japan and <80 or >=80 years old elsewhere].
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.12
Confidence Interval (2-Sided) 95%
0.76 to 1.65
Estimation Comments Hazard Ratio (HR) and Wald confidence intervals are derived from a Cox proportional-hazard model
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Dabigatran Etexilate 150mg, Warfarin (Excluding Elder Patients Outside USA)
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4414
Comments Wald 2-sided p-value from (unstratified) Cox proportional hazards model
Method Regression, Cox
Comments unstratified Cox proportional hazards model was used and elderly patients outside the USA were excluded
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.83
Confidence Interval (2-Sided) 95%
0.51 to 1.34
Estimation Comments Hazard Ratio (HR) and Wald confidence intervals are derived from a Cox proportional-hazard model
6.Secondary Outcome
Title Time to First Adjudicated MI
Hide Description Time to event analysis of patients with first adjudicated Myocardial Infarction (MI). The number of observed patients with adjudicated MI was reported
Time Frame up to 30 months
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis set (FAS) following the intention-to-treat principle.
Arm/Group Title Dabigatran Etexilate 110mg Dabigatran Etexilate 150mg Warfarin Warfarin (Excluding Elder Patients Outside USA)
Hide Arm/Group Description:
Patients were orally administered Dabigatran Etexilate 110mg capsule twice daily (BID) for at least 6 months.
Patients were orally administered Dabigatran Etexilate 150mg capsule twice daily (BID) for at least 6 months.
Patients were orally administered warfarin 1 mg, 3 mg, or 5 mg tablets once daily for at least 6 months. The warfarin dose was titrated as needed to maintain the target International normalised ratio (INR) of 2.0 to 3.0 (2.0 to 2.6 for Japanese patients aged ≥70 years); 2.0 to 2.5 if feasible
Patients were orally administered warfarin once daily. The warfarin dose was titrated as needed to maintain the target INR of 2.0 to 3.0 ; 2.0 to 2.5 if feasible. Elderly patients who were outside the USA were excluded.
Overall Number of Participants Analyzed 981 763 981 764
Measure Type: Count of Participants
Unit of Measure: Participants
44
   4.5%
26
   3.4%
29
   3.0%
22
   2.9%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dabigatran Etexilate 110mg, Warfarin
Comments [Not Specified]
Type of Statistical Test Other
Comments Wald 2-sided p-value from (stratified) Cox proportional hazards model
Statistical Test of Hypothesis P-Value 0.0861
Comments [Not Specified]
Method Regression, Cox
Comments The Cox proportional hazard model is stratified by age, non−elderly vs elderly [<70 or >=70 in Japan and <80 or >=80 years old elsewhere].
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.51
Confidence Interval (2-Sided) 95%
0.94 to 2.41
Estimation Comments Hazard Ratio (HR) and Wald confidence intervals are derived from a Cox proportional-hazard model
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Dabigatran Etexilate 150mg, Warfarin (Excluding Elder Patients Outside USA)
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6144
Comments Wald 2-sided p-value from (unstratified) Cox proportional hazards model
Method Regression, Cox
Comments unstratified Cox proportional hazards model was used and elderly patients outside the USA were excluded from
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.16
Confidence Interval (2-Sided) 95%
0.66 to 2.04
Estimation Comments Hazard Ratio (HR) and Wald confidence intervals are derived from a Cox proportional-hazard model
7.Secondary Outcome
Title Time to First Adjudicated Stroke
Hide Description

Time to event analysis of patients with first adjudicated Stroke. The number of observed patients with adjudicated Stroke was reported.

Stroke was defined as an acute episode of focal or global neurological dysfunction caused by brain, spinal cord, or retinal vascular injury as a result of haemorrhage or infarction

Time Frame up to 30 months
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis set (FAS) following the intention-to-treat principle.
Arm/Group Title Dabigatran Etexilate 110mg Dabigatran Etexilate 150mg Warfarin Warfarin (Excluding Elder Patients Outside USA)
Hide Arm/Group Description:
Patients were orally administered Dabigatran Etexilate 110mg capsule twice daily (BID) for at least 6 months.
Patients were orally administered Dabigatran Etexilate 150mg capsule twice daily (BID) for at least 6 months.
Patients were orally administered warfarin 1 mg, 3 mg, or 5 mg tablets once daily for at least 6 months. The warfarin dose was titrated as needed to maintain the target International normalised ratio (INR) of 2.0 to 3.0 (2.0 to 2.6 for Japanese patients aged ≥70 years); 2.0 to 2.5 if feasible
Patients were orally administered warfarin once daily. The warfarin dose was titrated as needed to maintain the target INR of 2.0 to 3.0 ; 2.0 to 2.5 if feasible. Elderly patients who were outside the USA were excluded.
Overall Number of Participants Analyzed 981 763 981 764
Measure Type: Count of Participants
Unit of Measure: Participants
17
   1.7%
9
   1.2%
13
   1.3%
8
   1.0%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dabigatran Etexilate 110mg, Warfarin
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4803
Comments Wald 2-sided p-value from (stratified) Cox proportional hazards model
Method Regression, Cox
Comments The Cox proportional hazard model is stratified by age, non−elderly vs elderly [<70 or >=70 in Japan and <80 or >=80 years old elsewhere].
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.30
Confidence Interval (2-Sided) 95%
0.63 to 2.67
Estimation Comments Hazard Ratio (HR) and Wald confidence intervals are derived from a Cox proportional-hazard model
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Dabigatran Etexilate 150mg, Warfarin (Excluding Elder Patients Outside USA)
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8537
Comments Wald 2-sided p-value from (unstratified) Cox proportional hazards model
Method Regression, Cox
Comments unstratified Cox proportional hazards model was used and elderly patients outside the USA were excluded from
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.09
Confidence Interval (2-Sided) 95%
0.42 to 2.83
Estimation Comments Hazard Ratio (HR) and Wald confidence intervals are derived from a Cox proportional-hazard model
8.Secondary Outcome
Title Time to First Adjudicated SE
Hide Description

Time to event analysis of patients with first adjudicated Systemic embolism (SE). The number of observed patients with adjudicated SE was reported.

SE is an acute vascular occlusion of the extremities or any organ (kidneys, mesenteric arteries, spleen, retina or grafts) and had to be documented by angiography, surgery, scintigraphy, or autopsy.

Time Frame up to 30 months
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis set (FAS) following the intention-to-treat principle.
Arm/Group Title Dabigatran Etexilate 110mg Dabigatran Etexilate 150mg Warfarin Warfarin (Excluding Elder Patients Outside USA)
Hide Arm/Group Description:
Patients were orally administered Dabigatran Etexilate 110mg capsule twice daily (BID) for at least 6 months.
Patients were orally administered Dabigatran Etexilate 150mg capsule twice daily (BID) for at least 6 months.
Patients were orally administered warfarin 1 mg, 3 mg, or 5 mg tablets once daily for at least 6 months. The warfarin dose was titrated as needed to maintain the target International normalised ratio (INR) of 2.0 to 3.0 (2.0 to 2.6 for Japanese patients aged ≥70 years); 2.0 to 2.5 if feasible
Patients were orally administered warfarin once daily. The warfarin dose was titrated as needed to maintain the target INR of 2.0 to 3.0 ; 2.0 to 2.5 if feasible. Elderly patients who were outside the USA were excluded.
Overall Number of Participants Analyzed 981 763 981 764
Measure Type: Count of Participants
Unit of Measure: Participants
3
   0.3%
1
   0.1%
3
   0.3%
3
   0.4%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dabigatran Etexilate 110mg, Warfarin
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9388
Comments Wald 2-sided p-value from (stratified) Cox proportional hazards model
Method Regression, Cox
Comments The Cox proportional hazard model is stratified by age, non−elderly vs elderly [<70 or >=70 in Japan and <80 or >=80 years old elsewhere].
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.94
Confidence Interval (2-Sided) 95%
0.19 to 4.66
Estimation Comments Hazard Ratio (HR) and Wald confidence intervals are derived from a Cox proportional-hazard model
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Dabigatran Etexilate 150mg, Warfarin (Excluding Elder Patients Outside USA)
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3030
Comments Wald 2-sided p-value from (unstratified) Cox proportional hazards model
Method Regression, Cox
Comments unstratified Cox proportional hazards model was used and elderly patients outside the USA were excluded from
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.30
Confidence Interval (2-Sided) 95%
0.03 to 2.93
Estimation Comments Hazard Ratio (HR) and Wald confidence intervals are derived from a Cox proportional-hazard model
9.Secondary Outcome
Title Time to First Adjudicated ST
Hide Description Time to event analysis of patients with first adjudicated Stent Thrombosis (ST). The number of observed patients with adjudicated ST was reported.
Time Frame up to 30 months
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis set (FAS) following the intention-to-treat principle.
Arm/Group Title Dabigatran Etexilate 110mg Dabigatran Etexilate 150mg Warfarin Warfarin (Excluding Elder Patients Outside USA)
Hide Arm/Group Description:
Patients were orally administered Dabigatran Etexilate 110mg capsule twice daily (BID) for at least 6 months.
Patients were orally administered Dabigatran Etexilate 150mg capsule twice daily (BID) for at least 6 months.
Patients were orally administered warfarin 1 mg, 3 mg, or 5 mg tablets once daily for at least 6 months. The warfarin dose was titrated as needed to maintain the target International normalised ratio (INR) of 2.0 to 3.0 (2.0 to 2.6 for Japanese patients aged ≥70 years); 2.0 to 2.5 if feasible
Patients were orally administered warfarin once daily. The warfarin dose was titrated as needed to maintain the target INR of 2.0 to 3.0 ; 2.0 to 2.5 if feasible. Elderly patients who were outside the USA were excluded.
Overall Number of Participants Analyzed 981 763 981 764
Measure Type: Count of Participants
Unit of Measure: Participants
15
   1.5%
7
   0.9%
8
   0.8%
7
   0.9%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dabigatran Etexilate 110mg, Warfarin
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1546
Comments Wald 2-sided p-value from (stratified) Cox proportional hazards model
Method Regression, Cox
Comments The Cox proportional hazard model is stratified by age, non−elderly vs elderly [<70 or >=70 in Japan and <80 or >=80 years old elsewhere].
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.86
Confidence Interval (2-Sided) 95%
0.79 to 4.40
Estimation Comments Hazard Ratio (HR) and Wald confidence intervals are derived from a Cox proportional-hazard model
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Dabigatran Etexilate 150mg, Warfarin (Excluding Elder Patients Outside USA)
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9789
Comments Wald 2-sided p-value from (unstratified) Cox proportional hazards model
Method Regression, Cox
Comments unstratified Cox proportional hazards model was used and elderly patients outside the USA were excluded from
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.99
Confidence Interval (2-Sided) 95%
0.35 to 2.81
Estimation Comments Hazard Ratio (HR) and Wald confidence intervals are derived from a Cox proportional-hazard model
10.Secondary Outcome
Title Time to Composite Endpoint of Death + MI + Stroke
Hide Description Time to event analysis of patients with the composite endpoint of death + myocardial infarction (MI) + stroke. The number of observed patients with the composite endpoint of death + myocardial infarction (MI) + stroke was reported.
Time Frame up to 30 months
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis set (FAS) following the intention-to-treat principle.
Arm/Group Title Dabigatran Etexilate 110mg Dabigatran Etexilate 150mg Warfarin Warfarin (Excluding Elder Patients Outside USA)
Hide Arm/Group Description:
Patients were orally administered Dabigatran Etexilate 110mg capsule twice daily (BID) for at least 6 months.
Patients were orally administered Dabigatran Etexilate 150mg capsule twice daily (BID) for at least 6 months.
Patients were orally administered warfarin 1 mg, 3 mg, or 5 mg tablets once daily for at least 6 months. The warfarin dose was titrated as needed to maintain the target International normalised ratio (INR) of 2.0 to 3.0 (2.0 to 2.6 for Japanese patients aged ≥70 years); 2.0 to 2.5 if feasible
Patients were orally administered warfarin once daily. The warfarin dose was titrated as needed to maintain the target INR of 2.0 to 3.0 ; 2.0 to 2.5 if feasible. Elderly patients who were outside the USA were excluded.
Overall Number of Participants Analyzed 981 763 981 764
Measure Type: Count of Participants
Unit of Measure: Participants
107
  10.9%
60
   7.9%
80
   8.2%
57
   7.5%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dabigatran Etexilate 110mg, Warfarin
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0484
Comments Wald 2-sided p-value from (stratified) Cox proportional hazards model
Method Regression, Cox
Comments The Cox proportional hazard model is stratified by age, non−elderly vs elderly [<70 or >=70 in Japan and <80 or >=80 years old elsewhere].
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.34
Confidence Interval (2-Sided) 95%
1.00 to 1.79
Estimation Comments Hazard Ratio (HR) and Wald confidence intervals are derived from a Cox proportional-hazard model
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Dabigatran Etexilate 150mg, Warfarin (Excluding Elder Patients Outside USA)
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8903
Comments Wald 2-sided p-value from (unstratified) Cox proportional hazards model
Method Regression, Cox
Comments unstratified Cox proportional hazards model was used and elderly patients outside the USA were excluded from
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.03
Confidence Interval (2-Sided) 95%
0.71 to 1.47
Estimation Comments Hazard Ratio (HR) and Wald confidence intervals are derived from a Cox proportional-hazard model
11.Secondary Outcome
Title Time to Composite Endpoint of Death or First Thrombotic Event
Hide Description Time to event analysis of patients with composite endpoint of death or first thrombotic event (all death, myocardial infarction (MI), stroke/systemic embolism (SE)). The number of observed patients with composite endpoint of death or thrombotic event (all death, MI, stroke/SE).
Time Frame up to 30 months
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis set (FAS) following the intention-to-treat principle.
Arm/Group Title Dabigatran Etexilate 110mg Dabigatran Etexilate 150mg Warfarin Warfarin (Excluding Elder Patients Outside USA All Dabigatran Etexilate
Hide Arm/Group Description:
Patients were orally administered Dabigatran Etexilate 110mg capsule twice daily (BID) for at least 6 months.
Patients were orally administered Dabigatran Etexilate 150mg capsule twice daily (BID) for at least 6 months.
Patients were orally administered warfarin 1 mg, 3 mg, or 5 mg tablets once daily for at least 6 months. The warfarin dose was titrated as needed to maintain the target International normalised ratio (INR) of 2.0 to 3.0 (2.0 to 2.6 for Japanese patients aged ≥70 years); 2.0 to 2.5 if feasible
Patients were orally administered warfarin once daily. The warfarin dose was titrated as needed to maintain the target INR of 2.0 to 3.0 ; 2.0 to 2.5 if feasible. Elderly patients who were outside the USA were excluded.
Patients in combined Dabigatran Etexilate group (ie 110 mg DE + 150 mg DE).
Overall Number of Participants Analyzed 981 763 981 764 1744
Measure Type: Count of Participants
Unit of Measure: Participants
108
  11.0%
60
   7.9%
83
   8.5%
60
   7.9%
168
   9.6%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Warfarin, All Dabigatran Etexilate
Comments A pre-defined hierarchical testing approach was used. This was the fifth step in hierarchy.
Type of Statistical Test Non-Inferiority
Comments All non-inferiority tests were based on a margin of 1.38.
Statistical Test of Hypothesis P-Value 0.1128
Comments P values for noninferiority were calculated at a one-sided alpha level of 0.025
Method Regression, Cox
Comments The Cox proportional hazard model is stratified by age, non−elderly vs elderly [<70 or >=70 in Japan and <80 or >=80 years old elsewhere].
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.17
Confidence Interval (2-Sided) 95%
0.90 to 1.53
Estimation Comments The upper bound of the Wald confidence interval (CI) of the HR of All Dabigatran Etexilate (110mg and 150 mg) vs Warfarin (one-sided 97.5%) was compared with this noninferiority margin for the testing of non-inferiority
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Dabigatran Etexilate 110mg, Warfarin
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0720
Comments Wald 2-sided p-value from (stratified) Cox proportional hazards model
Method Regression, Cox
Comments The Cox proportional hazard model is stratified by age, non−elderly vs elderly [<70 or >=70 in Japan and <80 or >=80 years old elsewhere].
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.30
Confidence Interval (2-Sided) 95%
0.98 to 1.73
Estimation Comments Hazard Ratio (HR) and Wald confidence intervals are derived from a Cox proportional-hazard model
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Dabigatran Etexilate 150mg, Warfarin (Excluding Elder Patients Outside USA
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8750
Comments Wald 2-sided p-value from (unstratified) Cox proportional hazards model
Method Regression, Cox
Comments unstratified Cox proportional hazards model was used and elderly patients outside the USA were excluded
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.97
Confidence Interval (2-Sided) 95%
0.68 to 1.39
Estimation Comments Hazard Ratio (HR) and Wald confidence intervals are derived from a Cox proportional-hazard model
12.Secondary Outcome
Title Time to First Adjudicated Unplanned Revascularisation by PCI/CABG
Hide Description Time to event analysis of patients with adjudicated unplanned revascularisation by Percutaneous Coronary Intervention (PCI)/Coronary Artery Bypass Graft (CABG). The number of observed patients with adjudicated unplanned revascularisation by PCI/CABG was reported.
Time Frame up to 30 months
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis set (FAS) following the intention-to-treat principle.
Arm/Group Title Dabigatran Etexilate 110mg Dabigatran Etexilate 150mg Warfarin Warfarin (Excluding Elder Patients Outside USA)
Hide Arm/Group Description:
Patients were orally administered Dabigatran Etexilate 110mg capsule twice daily (BID) for at least 6 months.
Patients were orally administered Dabigatran Etexilate 150mg capsule twice daily (BID) for at least 6 months.
Patients were orally administered warfarin 1 mg, 3 mg, or 5 mg tablets once daily for at least 6 months. The warfarin dose was titrated as needed to maintain the target International normalised ratio (INR) of 2.0 to 3.0 (2.0 to 2.6 for Japanese patients aged ≥70 years); 2.0 to 2.5 if feasible
Patients were orally administered warfarin once daily. The warfarin dose was titrated as needed to maintain the target INR of 2.0 to 3.0 ; 2.0 to 2.5 if feasible. Elderly patients who were outside the USA were excluded.
Overall Number of Participants Analyzed 981 763 981 764
Measure Type: Count of Participants
Unit of Measure: Participants
76
   7.7%
51
   6.7%
69
   7.0%
52
   6.8%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dabigatran Etexilate 110mg, Warfarin
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6080
Comments Wald 2-sided p-value from (stratified) Cox proportional hazards model
Method Regression, Cox
Comments The Cox proportional hazard model is stratified by age, non−elderly vs elderly [<70 or >=70 in Japan and <80 or >=80 years old elsewhere].
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.09
Confidence Interval (2-Sided) 95%
0.79 to 1.51
Estimation Comments Hazard Ratio (HR) and Wald confidence intervals are derived from a Cox proportional-hazard model
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Dabigatran Etexilate 150mg, Warfarin (Excluding Elder Patients Outside USA)
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8348
Comments Wald 2-sided p-value from (unstratified) Cox proportional hazards model
Method Regression, Cox
Comments unstratified Cox proportional hazards model was used and elderly patients outside the USA were excluded from
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.96
Confidence Interval (2-Sided) 95%
0.65 to 1.41
Estimation Comments Hazard Ratio (HR) and Wald confidence intervals are derived from a Cox proportional-hazard model
13.Secondary Outcome
Title Time to Death or First Thrombotic Event or Unplanned Revascularisation by PCI/CABG
Hide Description Time to event analysis of patients with death or thrombotic event (all death, myocardial infarction, stroke/systemic embolism) or unplanned revascularisation by Percutaneous Coronary Intervention/Coronary Artery Bypass Graft. The number of observed patients with death or first thrombotic event or unplanned revascularisation by PCI/CABG was reported.
Time Frame up to 30 months
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis set (FAS) following the intention-to-treat principle.
Arm/Group Title Dabigatran Etexilate 110mg Dabigatran Etexilate 150mg Warfarin Warfarin (Excluding Elder Patients Outside USA) All Dabigatran Etexilate
Hide Arm/Group Description:
Patients were orally administered Dabigatran Etexilate 110mg capsule twice daily (BID) for at least 6 months.
Patients were orally administered Dabigatran Etexilate 150mg capsule twice daily (BID) for at least 6 months.
Patients were orally administered warfarin 1 mg, 3 mg, or 5 mg tablets once daily for at least 6 months. The warfarin dose was titrated as needed to maintain the target International normalised ratio (INR) of 2.0 to 3.0 (2.0 to 2.6 for Japanese patients aged ≥70 years); 2.0 to 2.5 if feasible
Patients were orally administered warfarin once daily. The warfarin dose was titrated as needed to maintain the target INR of 2.0 to 3.0 ; 2.0 to 2.5 if feasible. Elderly patients who were outside the USA were excluded.
Patients in combined Dabigatran Etexilate group (ie 110 mg DE + 150 mg DE).
Overall Number of Participants Analyzed 981 763 981 764 1744
Measure Type: Count of Participants
Unit of Measure: Participants
149
  15.2%
90
  11.8%
131
  13.4%
98
  12.8%
239
  13.7%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Warfarin, All Dabigatran Etexilate
Comments A pre-defined hierarchical testing approach was used. This was the third step in hierarchy.
Type of Statistical Test Non-Inferiority
Comments All non-inferiority tests were based on a margin of 1.38.
Statistical Test of Hypothesis P-Value 0.0047
Comments P values for noninferiority were calculated at a one-sided alpha level of 0.025
Method Regression, Cox
Comments The Cox proportional hazard model is stratified by age, non−elderly vs elderly [<70 or >=70 in Japan and <80 or >=80 years old elsewhere].
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.04
Confidence Interval (2-Sided) 95%
0.84 to 1.29
Estimation Comments The upper bound of the Wald confidence interval (CI) of the HR of All Dabigatran Etexilate (110mg and 150 mg) vs Warfarin (one-sided 97.5%) was compared with this noninferiority margin for the testing of non-inferiority
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Dabigatran Etexilate 110mg, Warfarin
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3002
Comments Wald 2-sided p-value from (stratified) Cox proportional hazards model
Method Regression, Cox
Comments The Cox proportional hazard model is stratified by age, non−elderly vs elderly [<70 or >=70 in Japan and <80 or >=80 years old elsewhere].
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.13
Confidence Interval (2-Sided) 95%
0.90 to 1.43
Estimation Comments Hazard Ratio (HR) and Wald confidence intervals are derived from a Cox proportional-hazard model
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Dabigatran Etexilate 150mg, Warfarin (Excluding Elder Patients Outside USA)
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4432
Comments Wald 2-sided p-value from (unstratified) Cox proportional hazards model
Method Regression, Cox
Comments unstratified Cox proportional hazards model was used and elderly patients outside the USA were excluded
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.89
Confidence Interval (2-Sided) 95%
0.67 to 1.19
Estimation Comments Hazard Ratio (HR) and Wald confidence intervals are derived from a Cox proportional-hazard model
Time Frame From the first intake of randomised trial drug until 6 days after the last intake of the randomised trial drug, ie., up to 31 Months.
Adverse Event Reporting Description

Treated set (TS): The set of patients who received at least 1 dose of trial medication was analysed according to the treatment they had received. The start date of the observation period for this analysis set was the date of the first intake of trial medication.

All on-treatement AE's for this study were reported based on the Treated set

 
Arm/Group Title Dabigatran Etexilate 110mg Dabigatran Etexilate 150mg Warfarin
Hide Arm/Group Description Patients were orally administered Dabigatran Etexilate 110mg capsule twice daily (BID) for at least 6 months. Patients were orally administered Dabigatran Etexilate 150mg capsule twice daily (BID) for at least 6 months. Patients were orally administered warfarin 1 mg, 3 mg, or 5 mg tablets once daily for at least 6 months. The warfarin dose was titrated as needed to maintain the target International normalised ratio (INR) of 2.0 to 3.0 (2.0 to 2.6 for Japanese patients aged ≥70 years); 2.0 to 2.5 if feasible
All-Cause Mortality
Dabigatran Etexilate 110mg Dabigatran Etexilate 150mg Warfarin
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   38/972 (3.91%)   24/758 (3.17%)   41/948 (4.32%) 
Show Serious Adverse Events Hide Serious Adverse Events
Dabigatran Etexilate 110mg Dabigatran Etexilate 150mg Warfarin
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   415/972 (42.70%)   300/758 (39.58%)   396/948 (41.77%) 
Blood and lymphatic system disorders       
Anaemia  1  6/972 (0.62%)  7/758 (0.92%)  7/948 (0.74%) 
Anaemia macrocytic  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Haemorrhagic anaemia  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Iron deficiency anaemia  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Lymphadenopathy  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Normochromic normocytic anaemia  1  0/972 (0.00%)  1/758 (0.13%)  1/948 (0.11%) 
Thrombocytopenia  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Cardiac disorders       
Acute coronary syndrome  1  1/972 (0.10%)  2/758 (0.26%)  4/948 (0.42%) 
Acute left ventricular failure  1  1/972 (0.10%)  1/758 (0.13%)  0/948 (0.00%) 
Acute myocardial infarction  1  20/972 (2.06%)  14/758 (1.85%)  15/948 (1.58%) 
Acute right ventricular failure  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Angina pectoris  1  20/972 (2.06%)  18/758 (2.37%)  18/948 (1.90%) 
Angina unstable  1  26/972 (2.67%)  15/758 (1.98%)  13/948 (1.37%) 
Aortic valve disease  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Aortic valve disease mixed  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Aortic valve incompetence  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Aortic valve stenosis  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Arrhythmia  1  2/972 (0.21%)  2/758 (0.26%)  0/948 (0.00%) 
Arrhythmia supraventricular  1  1/972 (0.10%)  0/758 (0.00%)  1/948 (0.11%) 
Arteriosclerosis coronary artery  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Atrial fibrillation  1  44/972 (4.53%)  36/758 (4.75%)  34/948 (3.59%) 
Atrial flutter  1  18/972 (1.85%)  8/758 (1.06%)  6/948 (0.63%) 
Atrial tachycardia  1  1/972 (0.10%)  1/758 (0.13%)  0/948 (0.00%) 
Atrial thrombosis  1  2/972 (0.21%)  1/758 (0.13%)  1/948 (0.11%) 
Atrioventricular block second degree  1  0/972 (0.00%)  1/758 (0.13%)  1/948 (0.11%) 
Bradyarrhythmia  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Bradycardia  1  5/972 (0.51%)  5/758 (0.66%)  6/948 (0.63%) 
Cardiac arrest  1  4/972 (0.41%)  1/758 (0.13%)  5/948 (0.53%) 
Cardiac asthma  1  0/972 (0.00%)  1/758 (0.13%)  1/948 (0.11%) 
Cardiac failure  1  48/972 (4.94%)  30/758 (3.96%)  46/948 (4.85%) 
Cardiac failure acute  1  7/972 (0.72%)  5/758 (0.66%)  4/948 (0.42%) 
Cardiac failure chronic  1  7/972 (0.72%)  1/758 (0.13%)  3/948 (0.32%) 
Cardiac failure congestive  1  14/972 (1.44%)  13/758 (1.72%)  19/948 (2.00%) 
Cardiac flutter  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Cardiac tamponade  1  1/972 (0.10%)  0/758 (0.00%)  1/948 (0.11%) 
Cardiac ventricular thrombosis  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Cardiogenic shock  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Coronary artery disease  1  6/972 (0.62%)  6/758 (0.79%)  7/948 (0.74%) 
Coronary artery insufficiency  1  0/972 (0.00%)  1/758 (0.13%)  2/948 (0.21%) 
Coronary artery occlusion  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Coronary artery stenosis  1  4/972 (0.41%)  12/758 (1.58%)  3/948 (0.32%) 
Heart valve incompetence  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Intracardiac thrombus  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Ischaemic cardiomyopathy  1  1/972 (0.10%)  2/758 (0.26%)  0/948 (0.00%) 
Left ventricular failure  1  3/972 (0.31%)  0/758 (0.00%)  0/948 (0.00%) 
Microvascular coronary artery disease  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Mitral valve incompetence  1  5/972 (0.51%)  0/758 (0.00%)  3/948 (0.32%) 
Mitral valve prolapse  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Myocardial fibrosis  1  0/972 (0.00%)  2/758 (0.26%)  0/948 (0.00%) 
Myocardial infarction  1  17/972 (1.75%)  8/758 (1.06%)  8/948 (0.84%) 
Myocardial ischaemia  1  3/972 (0.31%)  1/758 (0.13%)  5/948 (0.53%) 
Palpitations  1  1/972 (0.10%)  0/758 (0.00%)  2/948 (0.21%) 
Pericardial effusion  1  2/972 (0.21%)  0/758 (0.00%)  0/948 (0.00%) 
Pericarditis  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Pericarditis constrictive  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Right ventricular failure  1  0/972 (0.00%)  1/758 (0.13%)  3/948 (0.32%) 
Silent myocardial infarction  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Sinus arrest  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Sinus bradycardia  1  1/972 (0.10%)  0/758 (0.00%)  1/948 (0.11%) 
Sinus node dysfunction  1  5/972 (0.51%)  2/758 (0.26%)  3/948 (0.32%) 
Supraventricular tachycardia  1  1/972 (0.10%)  1/758 (0.13%)  0/948 (0.00%) 
Systolic dysfunction  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Tachyarrhythmia  1  2/972 (0.21%)  2/758 (0.26%)  0/948 (0.00%) 
Tachycardia  1  2/972 (0.21%)  5/758 (0.66%)  1/948 (0.11%) 
Tricuspid valve incompetence  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Trifascicular block  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Ventricle rupture  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Ventricular arrhythmia  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Ventricular extrasystoles  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Ventricular fibrillation  1  3/972 (0.31%)  1/758 (0.13%)  0/948 (0.00%) 
Ventricular tachycardia  1  7/972 (0.72%)  5/758 (0.66%)  3/948 (0.32%) 
Congenital, familial and genetic disorders       
Generalised resistance to thyroid hormone  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Phimosis  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Venous angioma of brain  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Ear and labyrinth disorders       
Deafness  1  1/972 (0.10%)  0/758 (0.00%)  1/948 (0.11%) 
Vertigo  1  3/972 (0.31%)  3/758 (0.40%)  0/948 (0.00%) 
Vestibular disorder  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Endocrine disorders       
Thyroid mass  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Eye disorders       
Blindness transient  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Cataract  1  2/972 (0.21%)  3/758 (0.40%)  3/948 (0.32%) 
Eye haemorrhage  1  0/972 (0.00%)  1/758 (0.13%)  1/948 (0.11%) 
Glaucoma  1  3/972 (0.31%)  2/758 (0.26%)  2/948 (0.21%) 
Neovascular age-related macular degeneration  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Retinal detachment  1  1/972 (0.10%)  0/758 (0.00%)  3/948 (0.32%) 
Vitreous haemorrhage  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Gastrointestinal disorders       
Abdominal hernia  1  0/972 (0.00%)  1/758 (0.13%)  1/948 (0.11%) 
Abdominal pain  1  0/972 (0.00%)  3/758 (0.40%)  2/948 (0.21%) 
Abdominal pain upper  1  1/972 (0.10%)  2/758 (0.26%)  2/948 (0.21%) 
Chronic gastritis  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Colitis  1  2/972 (0.21%)  0/758 (0.00%)  0/948 (0.00%) 
Colitis ischaemic  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Dental cyst  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Diarrhoea  1  1/972 (0.10%)  1/758 (0.13%)  0/948 (0.00%) 
Diverticulum  1  0/972 (0.00%)  0/758 (0.00%)  2/948 (0.21%) 
Dyspepsia  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Dysphagia  1  2/972 (0.21%)  0/758 (0.00%)  1/948 (0.11%) 
Faecaloma  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Gastric haemorrhage  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Gastric polyps  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Gastritis  1  1/972 (0.10%)  0/758 (0.00%)  2/948 (0.21%) 
Gastritis erosive  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Gastritis haemorrhagic  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Gastrointestinal haemorrhage  1  9/972 (0.93%)  5/758 (0.66%)  13/948 (1.37%) 
Gastrointestinal polyp haemorrhage  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Gastrointestinal tract irritation  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Gastrooesophageal reflux disease  1  1/972 (0.10%)  1/758 (0.13%)  1/948 (0.11%) 
Gingival bleeding  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Haematemesis  1  1/972 (0.10%)  0/758 (0.00%)  2/948 (0.21%) 
Haematochezia  1  2/972 (0.21%)  3/758 (0.40%)  2/948 (0.21%) 
Hiatus hernia  1  1/972 (0.10%)  1/758 (0.13%)  0/948 (0.00%) 
Ileus  1  0/972 (0.00%)  2/758 (0.26%)  0/948 (0.00%) 
Incarcerated inguinal hernia  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Inguinal hernia  1  1/972 (0.10%)  0/758 (0.00%)  3/948 (0.32%) 
Intestinal haemorrhage  1  1/972 (0.10%)  0/758 (0.00%)  1/948 (0.11%) 
Intestinal obstruction  1  1/972 (0.10%)  0/758 (0.00%)  2/948 (0.21%) 
Large intestine polyp  1  1/972 (0.10%)  0/758 (0.00%)  2/948 (0.21%) 
Lower gastrointestinal haemorrhage  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Melaena  1  4/972 (0.41%)  1/758 (0.13%)  4/948 (0.42%) 
Nausea  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Oesophagitis  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Pancreatitis  1  1/972 (0.10%)  0/758 (0.00%)  1/948 (0.11%) 
Pancreatitis acute  1  1/972 (0.10%)  1/758 (0.13%)  0/948 (0.00%) 
Rectal haemorrhage  1  4/972 (0.41%)  3/758 (0.40%)  4/948 (0.42%) 
Rectal ulcer haemorrhage  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Retroperitoneal haematoma  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Small intestinal obstruction  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Stomach mass  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Upper gastrointestinal haemorrhage  1  0/972 (0.00%)  0/758 (0.00%)  2/948 (0.21%) 
Vomiting  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
General disorders       
Adverse drug reaction  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Asthenia  1  0/972 (0.00%)  0/758 (0.00%)  5/948 (0.53%) 
Cardiac death  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Chest discomfort  1  3/972 (0.31%)  1/758 (0.13%)  0/948 (0.00%) 
Chest pain  1  14/972 (1.44%)  15/758 (1.98%)  15/948 (1.58%) 
Death  1  8/972 (0.82%)  6/758 (0.79%)  5/948 (0.53%) 
Device related thrombosis  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Drug effect increased  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Gait disturbance  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
General physical health deterioration  1  0/972 (0.00%)  1/758 (0.13%)  1/948 (0.11%) 
Impaired healing  1  2/972 (0.21%)  1/758 (0.13%)  1/948 (0.11%) 
Implant site haematoma  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Injection site haematoma  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Localised oedema  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Malaise  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Medical device site haematoma  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Multiple organ dysfunction syndrome  1  1/972 (0.10%)  1/758 (0.13%)  0/948 (0.00%) 
Non-cardiac chest pain  1  3/972 (0.31%)  3/758 (0.40%)  1/948 (0.11%) 
Oedema  1  1/972 (0.10%)  1/758 (0.13%)  0/948 (0.00%) 
Oedema peripheral  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Puncture site haemorrhage  1  0/972 (0.00%)  0/758 (0.00%)  2/948 (0.21%) 
Pyrexia  1  1/972 (0.10%)  1/758 (0.13%)  1/948 (0.11%) 
Sudden cardiac death  1  4/972 (0.41%)  2/758 (0.26%)  1/948 (0.11%) 
Sudden death  1  2/972 (0.21%)  1/758 (0.13%)  7/948 (0.74%) 
Ulcer  1  1/972 (0.10%)  1/758 (0.13%)  0/948 (0.00%) 
Ulcer haemorrhage  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Vascular stent occlusion  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Vascular stent restenosis  1  5/972 (0.51%)  4/758 (0.53%)  3/948 (0.32%) 
Vascular stent stenosis  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Vascular stent thrombosis  1  25/972 (2.57%)  10/758 (1.32%)  17/948 (1.79%) 
Hepatobiliary disorders       
Bile duct obstruction  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Biliary cirrhosis primary  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Biliary colic  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Cholecystitis  1  4/972 (0.41%)  2/758 (0.26%)  4/948 (0.42%) 
Cholecystitis acute  1  2/972 (0.21%)  2/758 (0.26%)  1/948 (0.11%) 
Cholelithiasis  1  4/972 (0.41%)  1/758 (0.13%)  3/948 (0.32%) 
Drug-induced liver injury  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Gallbladder perforation  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Hepatic cirrhosis  1  0/972 (0.00%)  1/758 (0.13%)  1/948 (0.11%) 
Hepatic failure  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Hepatitis toxic  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Hepatomegaly  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Immune system disorders       
Drug hypersensitivity  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Infections and infestations       
Anal abscess  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Appendicitis  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Bone abscess  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Bronchiolitis  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Bronchitis  1  2/972 (0.21%)  2/758 (0.26%)  2/948 (0.21%) 
Candida infection  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Cellulitis  1  1/972 (0.10%)  6/758 (0.79%)  3/948 (0.32%) 
Cytomegalovirus infection  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Dengue fever  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Device related infection  1  2/972 (0.21%)  0/758 (0.00%)  0/948 (0.00%) 
Diabetic foot infection  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Diverticulitis intestinal haemorrhagic  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Empyema  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Endocarditis  1  2/972 (0.21%)  1/758 (0.13%)  0/948 (0.00%) 
Epididymitis  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Erysipelas  1  0/972 (0.00%)  2/758 (0.26%)  1/948 (0.11%) 
Escherichia sepsis  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Fungal oesophagitis  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Gangrene  1  2/972 (0.21%)  2/758 (0.26%)  0/948 (0.00%) 
Gastritis viral  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Gastroenteritis  1  1/972 (0.10%)  2/758 (0.26%)  1/948 (0.11%) 
Helicobacter infection  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Hepatitis C  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Infected cyst  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Infection  1  1/972 (0.10%)  1/758 (0.13%)  2/948 (0.21%) 
Infectious pleural effusion  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Infective exacerbation of chronic obstructive airways disease  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Influenza  1  2/972 (0.21%)  3/758 (0.40%)  3/948 (0.32%) 
Labyrinthitis  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Liver abscess  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Lower respiratory tract infection  1  1/972 (0.10%)  0/758 (0.00%)  1/948 (0.11%) 
Lung infection  1  0/972 (0.00%)  2/758 (0.26%)  1/948 (0.11%) 
Orchitis  1  1/972 (0.10%)  0/758 (0.00%)  1/948 (0.11%) 
Osteomyelitis  1  3/972 (0.31%)  1/758 (0.13%)  0/948 (0.00%) 
Pharyngitis  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Pneumonia  1  20/972 (2.06%)  15/758 (1.98%)  19/948 (2.00%) 
Pneumonia bacterial  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Pneumonia mycoplasmal  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Pseudomonas infection  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Pulmonary sepsis  1  0/972 (0.00%)  0/758 (0.00%)  2/948 (0.21%) 
Pyelonephritis  1  0/972 (0.00%)  2/758 (0.26%)  0/948 (0.00%) 
Pyelonephritis acute  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Renal abscess  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Respiratory tract infection  1  2/972 (0.21%)  0/758 (0.00%)  1/948 (0.11%) 
Respiratory tract infection viral  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Rhinovirus infection  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Scrotal abscess  1  2/972 (0.21%)  0/758 (0.00%)  1/948 (0.11%) 
Sepsis  1  5/972 (0.51%)  5/758 (0.66%)  4/948 (0.42%) 
Septic shock  1  0/972 (0.00%)  3/758 (0.40%)  2/948 (0.21%) 
Skin bacterial infection  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Soft tissue infection  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Staphylococcal bacteraemia  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Staphylococcal sepsis  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Systemic infection  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Upper respiratory tract infection  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Urinary tract infection  1  6/972 (0.62%)  3/758 (0.40%)  4/948 (0.42%) 
Urinary tract infection bacterial  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Urosepsis  1  3/972 (0.31%)  0/758 (0.00%)  1/948 (0.11%) 
Vestibular neuronitis  1  2/972 (0.21%)  2/758 (0.26%)  0/948 (0.00%) 
Viral infection  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Injury, poisoning and procedural complications       
Ankle fracture  1  2/972 (0.21%)  0/758 (0.00%)  0/948 (0.00%) 
Arterial bypass occlusion  1  1/972 (0.10%)  1/758 (0.13%)  0/948 (0.00%) 
Brain contusion  1  1/972 (0.10%)  0/758 (0.00%)  1/948 (0.11%) 
Chemical burn  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Clavicle fracture  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Concussion  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Confusion postoperative  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Contusion  1  1/972 (0.10%)  2/758 (0.26%)  1/948 (0.11%) 
Coronary artery restenosis  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Fall  1  4/972 (0.41%)  2/758 (0.26%)  5/948 (0.53%) 
Femoral neck fracture  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Femur fracture  1  0/972 (0.00%)  2/758 (0.26%)  1/948 (0.11%) 
Hand fracture  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Head injury  1  1/972 (0.10%)  0/758 (0.00%)  2/948 (0.21%) 
Hip fracture  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Iatrogenic injury  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Incisional hernia  1  1/972 (0.10%)  0/758 (0.00%)  1/948 (0.11%) 
Infusion related reaction  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Joint injury  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Laceration  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Ligament injury  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Limb injury  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Lumbar vertebral fracture  1  0/972 (0.00%)  1/758 (0.13%)  2/948 (0.21%) 
Meniscus injury  1  0/972 (0.00%)  1/758 (0.13%)  1/948 (0.11%) 
Multiple fractures  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Near drowning  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Overdose  1  0/972 (0.00%)  0/758 (0.00%)  3/948 (0.32%) 
Pelvic fracture  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Periprosthetic fracture  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Post procedural complication  1  2/972 (0.21%)  0/758 (0.00%)  1/948 (0.11%) 
Post procedural haemorrhage  1  1/972 (0.10%)  0/758 (0.00%)  2/948 (0.21%) 
Post procedural myocardial infarction  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Postoperative fever  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Postoperative renal failure  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Postoperative thrombosis  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Procedural complication  1  1/972 (0.10%)  1/758 (0.13%)  0/948 (0.00%) 
Pubis fracture  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Rib fracture  1  1/972 (0.10%)  0/758 (0.00%)  3/948 (0.32%) 
Road traffic accident  1  0/972 (0.00%)  0/758 (0.00%)  2/948 (0.21%) 
Skull fracture  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Skull fractured base  1  1/972 (0.10%)  0/758 (0.00%)  1/948 (0.11%) 
Spinal compression fracture  1  0/972 (0.00%)  0/758 (0.00%)  2/948 (0.21%) 
Splenic injury  1  1/972 (0.10%)  1/758 (0.13%)  0/948 (0.00%) 
Sternal fracture  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Subarachnoid haemorrhage  1  1/972 (0.10%)  0/758 (0.00%)  1/948 (0.11%) 
Subdural haematoma  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Subdural haemorrhage  1  1/972 (0.10%)  0/758 (0.00%)  1/948 (0.11%) 
Toxicity to various agents  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Traumatic intracranial haemorrhage  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Upper limb fracture  1  1/972 (0.10%)  1/758 (0.13%)  0/948 (0.00%) 
Vascular graft occlusion  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Vascular pseudoaneurysm  1  1/972 (0.10%)  1/758 (0.13%)  3/948 (0.32%) 
Wound  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Wound dehiscence  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Wrist fracture  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Investigations       
Anticoagulation drug level above therapeutic  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Blood creatinine increased  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Blood pressure abnormal  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Blood pressure increased  1  0/972 (0.00%)  1/758 (0.13%)  1/948 (0.11%) 
Blood urine  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Blood urine present  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
C-reactive protein increased  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Haematocrit decreased  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Haemoglobin decreased  1  0/972 (0.00%)  4/758 (0.53%)  2/948 (0.21%) 
Hepatic enzyme increased  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
International normalised ratio increased  1  0/972 (0.00%)  0/758 (0.00%)  9/948 (0.95%) 
Liver function test increased  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Occult blood positive  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Troponin increased  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Metabolism and nutrition disorders       
Dehydration  1  2/972 (0.21%)  0/758 (0.00%)  2/948 (0.21%) 
Diabetes mellitus  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Diabetes mellitus inadequate control  1  1/972 (0.10%)  0/758 (0.00%)  2/948 (0.21%) 
Diabetic metabolic decompensation  1  1/972 (0.10%)  0/758 (0.00%)  1/948 (0.11%) 
Gout  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Hyperglycaemia  1  3/972 (0.31%)  1/758 (0.13%)  4/948 (0.42%) 
Hyperhomocysteinaemia  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Hyperkalaemia  1  1/972 (0.10%)  2/758 (0.26%)  0/948 (0.00%) 
Hypernatraemia  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Hypoglycaemia  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Hypokalaemia  1  2/972 (0.21%)  0/758 (0.00%)  2/948 (0.21%) 
Hyponatraemia  1  3/972 (0.31%)  0/758 (0.00%)  1/948 (0.11%) 
Hypovolaemia  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Metabolic disorder  1  0/972 (0.00%)  0/758 (0.00%)  2/948 (0.21%) 
Metabolic syndrome  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Musculoskeletal and connective tissue disorders       
Arthralgia  1  0/972 (0.00%)  3/758 (0.40%)  2/948 (0.21%) 
Arthritis  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Bursitis  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Chondropathy  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Exostosis  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Haemarthrosis  1  0/972 (0.00%)  0/758 (0.00%)  3/948 (0.32%) 
Intervertebral disc protrusion  1  1/972 (0.10%)  1/758 (0.13%)  0/948 (0.00%) 
Joint swelling  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Muscle haemorrhage  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Musculoskeletal chest pain  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Musculoskeletal pain  1  1/972 (0.10%)  0/758 (0.00%)  2/948 (0.21%) 
Myalgia  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Osteoarthritis  1  7/972 (0.72%)  4/758 (0.53%)  2/948 (0.21%) 
Osteochondrosis  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Plica syndrome  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Polymyalgia rheumatica  1  1/972 (0.10%)  0/758 (0.00%)  1/948 (0.11%) 
Rheumatoid arthritis  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Rotator cuff syndrome  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Sacroiliitis  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Spinal column stenosis  1  0/972 (0.00%)  2/758 (0.26%)  1/948 (0.11%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Acoustic neuroma  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Adenocarcinoma gastric  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Adenocarcinoma of colon  1  3/972 (0.31%)  0/758 (0.00%)  0/948 (0.00%) 
B-cell lymphoma  1  1/972 (0.10%)  1/758 (0.13%)  1/948 (0.11%) 
Basal cell carcinoma  1  5/972 (0.51%)  1/758 (0.13%)  4/948 (0.42%) 
Benign gastrointestinal neoplasm  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Bladder cancer  1  2/972 (0.21%)  1/758 (0.13%)  0/948 (0.00%) 
Bladder cancer recurrent  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Bladder neoplasm  1  1/972 (0.10%)  1/758 (0.13%)  0/948 (0.00%) 
Bladder transitional cell carcinoma  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Bone neoplasm  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Breast cancer  1  1/972 (0.10%)  1/758 (0.13%)  0/948 (0.00%) 
Bronchial carcinoma  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Carcinoma in situ of penis  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Cerebral haemangioma  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Chronic lymphocytic leukaemia  1  0/972 (0.00%)  0/758 (0.00%)  2/948 (0.21%) 
Colon cancer  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Colon neoplasm  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Colorectal adenocarcinoma  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Colorectal cancer  1  0/972 (0.00%)  0/758 (0.00%)  2/948 (0.21%) 
Gastric cancer  1  0/972 (0.00%)  1/758 (0.13%)  1/948 (0.11%) 
Hepatocellular carcinoma  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Lung adenocarcinoma  1  1/972 (0.10%)  1/758 (0.13%)  0/948 (0.00%) 
Lung adenocarcinoma stage IV  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Lung cancer metastatic  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Lung carcinoma cell type unspecified stage I  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Lung neoplasm malignant  1  3/972 (0.31%)  0/758 (0.00%)  0/948 (0.00%) 
Lymphocytic leukaemia  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Lymphoma  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Malignant melanoma  1  1/972 (0.10%)  1/758 (0.13%)  1/948 (0.11%) 
Mantle cell lymphoma  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Meningioma  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Metastases to bone  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Metastases to liver  1  2/972 (0.21%)  0/758 (0.00%)  1/948 (0.11%) 
Metastases to lung  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Metastases to spine  1  1/972 (0.10%)  0/758 (0.00%)  1/948 (0.11%) 
Myelodysplastic syndrome  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Myelofibrosis  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Non-Hodgkin's lymphoma  1  0/972 (0.00%)  0/758 (0.00%)  2/948 (0.21%) 
Non-small cell lung cancer  1  1/972 (0.10%)  1/758 (0.13%)  0/948 (0.00%) 
Non-small cell lung cancer recurrent  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Pancreatic carcinoma  1  0/972 (0.00%)  1/758 (0.13%)  2/948 (0.21%) 
Plasma cell myeloma  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Prostate cancer  1  6/972 (0.62%)  2/758 (0.26%)  3/948 (0.32%) 
Rectal adenocarcinoma  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Rectal cancer  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Rectal cancer stage 0  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Renal cancer  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Renal cell carcinoma  1  1/972 (0.10%)  0/758 (0.00%)  1/948 (0.11%) 
Renal neoplasm  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Skin cancer  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Small cell lung cancer  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Squamous cell carcinoma  1  1/972 (0.10%)  1/758 (0.13%)  1/948 (0.11%) 
Squamous cell carcinoma of skin  1  1/972 (0.10%)  0/758 (0.00%)  1/948 (0.11%) 
Squamous cell carcinoma of the tongue  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Testicular neoplasm  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Transitional cell carcinoma  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Transitional cell carcinoma recurrent  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Tumour ulceration  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Urinary bladder adenoma  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Nervous system disorders       
Altered state of consciousness  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Basal ganglia haemorrhage  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Basal ganglia stroke  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Brain injury  1  0/972 (0.00%)  1/758 (0.13%)  1/948 (0.11%) 
Brain oedema  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Brain stem infarction  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Carotid arteriosclerosis  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Carotid artery occlusion  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Carotid artery stenosis  1  1/972 (0.10%)  1/758 (0.13%)  0/948 (0.00%) 
Carotid sinus syndrome  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Cerebellar haemorrhage  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Cerebral haemorrhage  1  0/972 (0.00%)  0/758 (0.00%)  2/948 (0.21%) 
Cerebral infarction  1  1/972 (0.10%)  1/758 (0.13%)  0/948 (0.00%) 
Cerebral ischaemia  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Cerebrovascular accident  1  3/972 (0.31%)  4/758 (0.53%)  4/948 (0.42%) 
Dementia  1  3/972 (0.31%)  1/758 (0.13%)  0/948 (0.00%) 
Diplegia  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Disturbance in attention  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Dizziness  1  2/972 (0.21%)  0/758 (0.00%)  3/948 (0.32%) 
Dizziness postural  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Drop attacks  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Encephalomalacia  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Encephalopathy  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Epilepsy  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Facial paresis  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Haemorrhage intracranial  1  1/972 (0.10%)  0/758 (0.00%)  1/948 (0.11%) 
Haemorrhagic stroke  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Headache  1  0/972 (0.00%)  3/758 (0.40%)  0/948 (0.00%) 
Hemiplegia  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Ischaemic stroke  1  4/972 (0.41%)  4/758 (0.53%)  1/948 (0.11%) 
Lacunar infarction  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Lateral medullary syndrome  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Loss of consciousness  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Mental impairment  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Metabolic encephalopathy  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Migraine  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Movement disorder  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Post herpetic neuralgia  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Quadriparesis  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Sciatica  1  1/972 (0.10%)  0/758 (0.00%)  1/948 (0.11%) 
Seizure  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Somnolence  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Spinal claudication  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Syncope  1  9/972 (0.93%)  10/758 (1.32%)  7/948 (0.74%) 
Tension headache  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Transient ischaemic attack  1  4/972 (0.41%)  1/758 (0.13%)  1/948 (0.11%) 
Product Issues       
Device malfunction  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Psychiatric disorders       
Alcohol abuse  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Anxiety  1  1/972 (0.10%)  0/758 (0.00%)  1/948 (0.11%) 
Anxiety disorder  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Confusional state  1  0/972 (0.00%)  0/758 (0.00%)  2/948 (0.21%) 
Delirium  1  3/972 (0.31%)  0/758 (0.00%)  0/948 (0.00%) 
Hallucination, visual  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Mental status changes  1  1/972 (0.10%)  1/758 (0.13%)  0/948 (0.00%) 
Paranoia  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Transient psychosis  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Renal and urinary disorders       
Acute kidney injury  1  15/972 (1.54%)  14/758 (1.85%)  6/948 (0.63%) 
Acute prerenal failure  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Calculus bladder  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Chronic kidney disease  1  1/972 (0.10%)  0/758 (0.00%)  1/948 (0.11%) 
Cystitis haemorrhagic  1  0/972 (0.00%)  0/758 (0.00%)  2/948 (0.21%) 
Haematuria  1  3/972 (0.31%)  4/758 (0.53%)  7/948 (0.74%) 
Haemorrhage urinary tract  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Nephrolithiasis  1  1/972 (0.10%)  3/758 (0.40%)  1/948 (0.11%) 
Renal cyst  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Renal failure  1  6/972 (0.62%)  3/758 (0.40%)  2/948 (0.21%) 
Renal impairment  1  3/972 (0.31%)  1/758 (0.13%)  1/948 (0.11%) 
Renal infarct  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Renal mass  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Urinary bladder haemorrhage  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Urinary tract obstruction  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Reproductive system and breast disorders       
Benign prostatic hyperplasia  1  2/972 (0.21%)  1/758 (0.13%)  0/948 (0.00%) 
Prostatitis  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Vaginal haemorrhage  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Acute pulmonary oedema  1  4/972 (0.41%)  1/758 (0.13%)  2/948 (0.21%) 
Acute respiratory failure  1  1/972 (0.10%)  3/758 (0.40%)  3/948 (0.32%) 
Asthma  1  0/972 (0.00%)  1/758 (0.13%)  1/948 (0.11%) 
Bronchiectasis  1  1/972 (0.10%)  1/758 (0.13%)  0/948 (0.00%) 
Bronchospasm  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Chronic obstructive pulmonary disease  1  5/972 (0.51%)  6/758 (0.79%)  6/948 (0.63%) 
Chronic respiratory failure  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Cough  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Dyspnoea  1  11/972 (1.13%)  10/758 (1.32%)  17/948 (1.79%) 
Dyspnoea at rest  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Dyspnoea exertional  1  2/972 (0.21%)  2/758 (0.26%)  0/948 (0.00%) 
Epistaxis  1  3/972 (0.31%)  3/758 (0.40%)  9/948 (0.95%) 
Haemoptysis  1  4/972 (0.41%)  2/758 (0.26%)  5/948 (0.53%) 
Haemothorax  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Hypoxia  1  0/972 (0.00%)  2/758 (0.26%)  0/948 (0.00%) 
Interstitial lung disease  1  0/972 (0.00%)  1/758 (0.13%)  1/948 (0.11%) 
Laryngeal oedema  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Lung disorder  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Pleural effusion  1  8/972 (0.82%)  0/758 (0.00%)  3/948 (0.32%) 
Pleurisy  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Pneumonia aspiration  1  1/972 (0.10%)  0/758 (0.00%)  1/948 (0.11%) 
Pneumothorax  1  3/972 (0.31%)  0/758 (0.00%)  1/948 (0.11%) 
Pulmonary embolism  1  1/972 (0.10%)  1/758 (0.13%)  2/948 (0.21%) 
Pulmonary fibrosis  1  1/972 (0.10%)  2/758 (0.26%)  0/948 (0.00%) 
Pulmonary hypertension  1  1/972 (0.10%)  1/758 (0.13%)  2/948 (0.21%) 
Pulmonary mass  1  0/972 (0.00%)  2/758 (0.26%)  0/948 (0.00%) 
Pulmonary oedema  1  7/972 (0.72%)  0/758 (0.00%)  1/948 (0.11%) 
Respiratory failure  1  1/972 (0.10%)  4/758 (0.53%)  1/948 (0.11%) 
Sleep apnoea syndrome  1  0/972 (0.00%)  1/758 (0.13%)  2/948 (0.21%) 
Skin and subcutaneous tissue disorders       
Dermatitis  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Dermatitis allergic  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Diabetic foot  1  1/972 (0.10%)  1/758 (0.13%)  2/948 (0.21%) 
Haemorrhage subcutaneous  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Pemphigoid  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Psoriasis  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Skin ulcer  1  1/972 (0.10%)  1/758 (0.13%)  1/948 (0.11%) 
Stasis dermatitis  1  1/972 (0.10%)  1/758 (0.13%)  0/948 (0.00%) 
Vascular disorders       
Aneurysm  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Angiodysplasia  1  1/972 (0.10%)  0/758 (0.00%)  1/948 (0.11%) 
Aortic aneurysm  1  1/972 (0.10%)  2/758 (0.26%)  1/948 (0.11%) 
Aortic dissection  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Aortic dissection rupture  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Aortic necrosis  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Aortic stenosis  1  3/972 (0.31%)  0/758 (0.00%)  2/948 (0.21%) 
Aortic thrombosis  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Aortitis  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Arterial occlusive disease  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Arteriovenous fistula  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Circulatory collapse  1  0/972 (0.00%)  1/758 (0.13%)  1/948 (0.11%) 
Diabetic vascular disorder  1  0/972 (0.00%)  1/758 (0.13%)  0/948 (0.00%) 
Extremity necrosis  1  1/972 (0.10%)  0/758 (0.00%)  1/948 (0.11%) 
Femoral artery dissection  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Haematoma  1  2/972 (0.21%)  1/758 (0.13%)  7/948 (0.74%) 
Haemorrhage  1  2/972 (0.21%)  2/758 (0.26%)  6/948 (0.63%) 
Hypertension  1  6/972 (0.62%)  5/758 (0.66%)  1/948 (0.11%) 
Hypertensive crisis  1  8/972 (0.82%)  3/758 (0.40%)  11/948 (1.16%) 
Hypertensive emergency  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Hypotension  1  1/972 (0.10%)  2/758 (0.26%)  6/948 (0.63%) 
Hypovolaemic shock  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Iliac artery occlusion  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Intermittent claudication  1  1/972 (0.10%)  1/758 (0.13%)  0/948 (0.00%) 
Ischaemia  1  1/972 (0.10%)  0/758 (0.00%)  1/948 (0.11%) 
Orthostatic hypotension  1  1/972 (0.10%)  0/758 (0.00%)  0/948 (0.00%) 
Peripheral arterial occlusive disease  1  5/972 (0.51%)  1/758 (0.13%)  5/948 (0.53%) 
Peripheral artery occlusion  1  0/972 (0.00%)  0/758 (0.00%)  2/948 (0.21%) 
Peripheral artery stenosis  1  1/972 (0.10%)  0/758 (0.00%)  1/948 (0.11%) 
Peripheral embolism  1  2/972 (0.21%)  0/758 (0.00%)  1/948 (0.11%) 
Peripheral ischaemia  1  0/972 (0.00%)  2/758 (0.26%)  0/948 (0.00%) 
Shock  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Temporal arteritis  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Thrombophlebitis superficial  1  0/972 (0.00%)  0/758 (0.00%)  1/948 (0.11%) 
Thrombosis  1  2/972 (0.21%)  0/758 (0.00%)  1/948 (0.11%) 
1
Term from vocabulary, MedDRA 20.0
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Dabigatran Etexilate 110mg Dabigatran Etexilate 150mg Warfarin
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   128/972 (13.17%)   126/758 (16.62%)   229/948 (24.16%) 
Respiratory, thoracic and mediastinal disorders       
Dyspnoea  1  62/972 (6.38%)  60/758 (7.92%)  61/948 (6.43%) 
Epistaxis  1  52/972 (5.35%)  59/758 (7.78%)  146/948 (15.40%) 
Vascular disorders       
Haematoma  1  27/972 (2.78%)  24/758 (3.17%)  60/948 (6.33%) 
1
Term from vocabulary, MedDRA 20.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Boehringer Ingelheim, Call Center
Organization: Boehringer Ingelheim
Phone: 1-800-243-0127
EMail: clintriage.rdg@boehringer-ingelheim.com
Layout table for additonal information
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT02164864     History of Changes
Other Study ID Numbers: 1160.186
2013-003201-26 ( EudraCT Number )
First Submitted: June 13, 2014
First Posted: June 17, 2014
Results First Submitted: June 5, 2018
Results First Posted: July 31, 2018
Last Update Posted: July 31, 2018