Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study Comparing Cardiovascular Effects of Ticagrelor and Clopidogrel in Patients With Peripheral Artery Disease (EUCLID)

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: NCT01732822
Recruitment Status : Completed
First Posted : November 26, 2012
Results First Posted : October 30, 2017
Last Update Posted : October 30, 2017
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Prevention
Condition Peripheral Artery Disease
Interventions Drug: Ticagrelor
Drug: Clopidogrel
Enrollment 13885
Recruitment Details This study was conducted at 821 centres randomising patients across 28 countries. The first patient was enrolled on 04 December 2012. The last visit of the last patient took place on 26 September 2016. In total, 16237 patients were screened.
Pre-assignment Details Screened patients randomised to study drug: 85.5%; n=13885 Patients who were not randomised: 14.5%; n=2352 Patients with inclusion criteria for symptomatic lower extremity PAD failed: n=489 Patients with poor metabolizer status for CYP2C19: n=616 Patients with other reason: n=1374
Arm/Group Title Ticagrelor 90 mg bd Clopidogrel 75 mg od
Hide Arm/Group Description [Not Specified] [Not Specified]
Period Title: Overall Study
Started 6930 6955
Completed 6807 [1] 6842 [1]
Not Completed 123 113
Reason Not Completed
Withdrawal by Subject             123             113
[1]
Includes patients who did not withdraw informed consent prior to the PACD
Arm/Group Title Ticagrelor 90mg bd Clopidogrel 75mg od Total
Hide Arm/Group Description [Not Specified] [Not Specified] Total of all reporting groups
Overall Number of Baseline Participants 6930 6955 13885
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Age Number Analyzed 6930 participants 6955 participants 13885 participants
66.6  (8.4) 66.5  (8.5) 66.6  (8.4)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 6930 participants 6955 participants 13885 participants
<65 years 2900 2985 5885
Between 65 and 75 years 2925 2850 5775
>75 years 1105 1120 2225
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6930 participants 6955 participants 13885 participants
Female
1908
  27.5%
1980
  28.5%
3888
  28.0%
Male
5022
  72.5%
4975
  71.5%
9997
  72.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 6930 participants 6955 participants 13885 participants
Hispanic Or Latino 1046 1067 2113
Not Hispanic Or Latino 5884 5888 11772
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 6930 participants 6955 participants 13885 participants
American Indian Or Alaska Native 63 62 125
Asian 824 810 1634
Black Or African American 280 289 569
Native Hawaiian Or Other Pacific Islander 2 3 5
Other 110 132 242
White 5651 5659 11310
1.Primary Outcome
Title Composite of Cardiovascular (CV) Death/MI/Ischemic Stroke
Hide Description Participants with CV death, myocardial infarction (MI) or ischemic stroke. If no event, censoring occurs at the minimum of (primary analysis censoring date (PACD), last endpoint assessment date, non-CV death date)
Time Frame From randomization to PACD, an average of 2.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
The population was the full analysis set, which included all randomized patients.
Arm/Group Title Ticagrelor 90 mg bd Clopidogrel 75 mg od
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 6930 6955
Measure Type: Number
Unit of Measure: Participants
751 740
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ticagrelor 90 mg bd, Clopidogrel 75 mg od
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.650
Comments The hypothesis will be tested at the 4.94% two-sided significance level to account for the planned interim analysis with the overall type I error preserved at 5%. A hierarchical test sequence will be used to address the issue of multiple testing
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.02
Confidence Interval (2-Sided) 95%
0.92 to 1.13
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Composite of CV Death, MI, Ischemic Stroke, and ALI
Hide Description Participants with CV death, MI, ischemic stroke or acute limb ischemia (ALI). If no event, censoring occurs at the minimum of (PACD, last endpoint assessment date, non-CV death date)
Time Frame From randomization to PACD, an average of 2.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
The population was the full analysis set, which included all randomized patients
Arm/Group Title Ticagrelor 90 mg bd Clopidogrel 75 mg od
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 6930 6955
Measure Type: Number
Unit of Measure: Participant
839 833
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ticagrelor 90 mg bd, Clopidogrel 75 mg od
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.738
Comments The hypothesis will be tested at the 4.94% two-sided significance level to account for the planned interim analysis with the overall type I error preserved at 5%. A hierarchical test sequence will be used to address the issue of multiple testing
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.02
Confidence Interval (2-Sided) 95%
0.92 to 1.12
Estimation Comments [Not Specified]
3.Secondary Outcome
Title CV Death
Hide Description Participants with CV death. If no event, censoring occurs at the minimum of (PACD, last endpoint assessment date, non-CV death date)
Time Frame From randomization to PACD, an average of 2.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
The population was the full analysis set, which included all randomized patients
Arm/Group Title Ticagrelor 90 mg bd Clopidogrel 75 mg od
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 6930 6955
Measure Type: Number
Unit of Measure: Participant
363 343
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ticagrelor 90 mg bd, Clopidogrel 75 mg od
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.400
Comments The hypothesis will be tested at the 4.94% two-sided significance level to account for the planned interim analysis with the overall type I error preserved at 5%. A hierarchical test sequence will be used to address the issue of multiple testing
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.07
Confidence Interval (2-Sided) 95%
0.92 to 1.23
Estimation Comments [Not Specified]
4.Secondary Outcome
Title MI
Hide Description Participants with MI. If no event, censoring occurs at the minimum of (PACD, last endpoint assessment date, death date)
Time Frame From randomization to PACD, an average of 2.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
The population was the full analysis set, which included all randomized patients
Arm/Group Title Ticagrelor 90 mg bd Clopidogrel 75 mg od
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 6930 6955
Measure Type: Number
Unit of Measure: Participant
349 334
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ticagrelor 90 mg bd, Clopidogrel 75 mg od
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.482
Comments The hypothesis will be tested at the 4.94% two-sided significance level to account for the planned interim analysis with the overall type I error preserved at 5%. A hierarchical test sequence will be used to address the issue of multiple testing
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.06
Confidence Interval (2-Sided) 95%
0.91 to 1.23
Estimation Comments [Not Specified]
5.Secondary Outcome
Title All-cause Mortality
Hide Description Participants with all-cause death. If no event, censoring occurs at the minimum of (PACD, last endpoint assessment date)
Time Frame From randomization to PACD, an average of 2.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
The population was the full analysis set, which included all randomized patients
Arm/Group Title Ticagrelor 90 mg bd Clopidogrel 75 mg od
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 6930 6955
Measure Type: Number
Unit of Measure: Participant
628 635
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ticagrelor 90 mg bd, Clopidogrel 75 mg od
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.913
Comments The hypothesis will be tested at the 4.94% two-sided significance level to account for the planned interim analysis with the overall type I error preserved at 5%. A hierarchical test sequence will be used to address the issue of multiple testing
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.99
Confidence Interval (2-Sided) 95%
0.89 to 1.11
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Composite of CV Death, MI, and All-cause Stroke (Ischemic or Hemorrhagic)
Hide Description Participants with CV death, MI or all-cause stroke. If no event, censoring occurs at the minimum of (PACD, last endpoint assessment date, non-CV death date)
Time Frame From randomization to PACD, an average of 2.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
The population was the full analysis set, which included all randomized patients
Arm/Group Title Ticagrelor 90 mg bd Clopidogrel 75 mg od
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 6930 6955
Measure Type: Number
Unit of Measure: Participant
766 759
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ticagrelor 90 mg bd, Clopidogrel 75 mg od
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.724
Comments The hypothesis will be tested at the 4.94% two-sided significance level to account for the planned interim analysis with the overall type I error preserved at 5%. A hierarchical test sequence will be used to address the issue of multiple testing
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.02
Confidence Interval (2-Sided) 95%
0.92 to 1.13
Estimation Comments [Not Specified]
7.Secondary Outcome
Title ALI
Hide Description Participants with ALI. If no event, censoring occurs at the minimum of (PACD, last endpoint assessment date, death date)
Time Frame From randomization to PACD, an average of 2.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
The population was the full analysis set, which included all randomized patients
Arm/Group Title Ticagrelor 90 mg bd Clopidogrel 75 mg od
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 6930 6955
Measure Type: Number
Unit of Measure: Participant
117 115
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ticagrelor 90 mg bd, Clopidogrel 75 mg od
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.846
Comments The hypothesis will be tested at the 4.94% two-sided significance level to account for the planned interim analysis with the overall type I error preserved at 5%. A hierarchical test sequence will be used to address the issue of multiple testing
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.03
Confidence Interval (2-Sided) 95%
0.79 to 1.33
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Lower Extremity Revascularization
Hide Description Participants with lower extremity revascularization (LER). If no event, censoring occurs at the minimum of (PACD, last endpoint assessment date, death date)
Time Frame From randomization to PACD, an average of 2.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
The population was the full analysis set, which included all randomized patients
Arm/Group Title Ticagrelor 90 mg bd Clopidogrel 75 mg od
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 6930 6955
Measure Type: Number
Unit of Measure: Participant
846 892
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ticagrelor 90 mg bd, Clopidogrel 75 mg od
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.298
Comments The hypothesis will be tested at the 4.94% two-sided significance level to account for the planned interim analysis with the overall type I error preserved at 5%. A hierarchical test sequence will be used to address the issue of multiple testing
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.95
Confidence Interval (2-Sided) 95%
0.87 to 1.05
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Any Revascularisation (Coronary, Peripheral [Limb, Mesenteric, Renal, Carotid and Other])
Hide Description Participants with any revascularization. If no event, censoring occurs at the minimum of (PACD, last endpoint assessment date, death date)
Time Frame From randomization to PACD, an average of 2.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
The population was the full analysis set, which included all randomized patients
Arm/Group Title Ticagrelor 90 mg bd Clopidogrel 75 mg od
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 6930 6955
Measure Type: Number
Unit of Measure: Participant
1211 1250
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ticagrelor 90 mg bd, Clopidogrel 75 mg od
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.462
Comments The hypothesis will be tested at the 4.94% two-sided significance level to account for the planned interim analysis with the overall type I error preserved at 5%. A hierarchical test sequence will be used to address the issue of multiple testing
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.97
Confidence Interval (2-Sided) 95%
0.90 to 1.05
Estimation Comments [Not Specified]
10.Other Pre-specified Outcome
Title Net Clinical Benefit (Composite of CV Death/MI/Ischemic Stroke/Fatal Bleeding/Intracranial Bleeding)
Hide Description Participants with CV death, MI, ischemic stroke, fatal bleeding or intracranial bleeding. If no event, censoring occurs at the minimum of (PACD, last endpoint assessment date, non-CV death date)
Time Frame From randomization to PACD, an average of 2.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
The population was the full analysis set, which included all randomized patients
Arm/Group Title Ticagrelor 90 mg bd Clopidogrel 75 mg od
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 6930 6955
Measure Type: Number
Unit of Measure: Participant
789 786
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ticagrelor 90 mg bd, Clopidogrel 75 mg od
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.793
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.01
Confidence Interval (2-Sided) 95%
0.92 to 1.12
Estimation Comments [Not Specified]
11.Other Pre-specified Outcome
Title Net Clinical Benefit (Composite of All-cause Mortality/MI/Ischemic Stroke/Fatal Bleeding/Intracranial Bleeding)
Hide Description Participants with all-cause death, MI, ischemic stroke, fatal bleeding or intracranial bleeding. If no event, censoring occurs at the minimum of (PACD, last endpoint assessment date)
Time Frame From randomization to PACD, an average of 2.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
The population was the full analysis set, which included all randomized patients
Arm/Group Title Ticagrelor 90 mg bd Clopidogrel 75 mg od
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 6930 6955
Measure Type: Number
Unit of Measure: Participant
983 992
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ticagrelor 90 mg bd, Clopidogrel 75 mg od
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.000
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.00
Confidence Interval (2-Sided) 95%
0.92 to 1.09
Estimation Comments [Not Specified]
12.Other Pre-specified Outcome
Title Net Clinical Benefit (Composite of All-cause Mortality/MI/Ischemic Stroke/ALI/Major Amputation/Fatal Bleeding/Intracranial Bleeding)
Hide Description Participants with all-cause death, MI, ischemic stroke, ALI, major amputation, fatal bleeding or intracranial bleeding. If no event, censoring occurs at the minimum of (PACD, last endpoint assessment date)
Time Frame From randomization to PACD, an average of 2.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
The population was the full analysis set, which included all randomized patients
Arm/Group Title Ticagrelor 90 mg bd Clopidogrel 75 mg od
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 6930 6955
Measure Type: Number
Unit of Measure: Participant
1119 1140
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ticagrelor 90 mg bd, Clopidogrel 75 mg od
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.829
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.99
Confidence Interval (2-Sided) 95%
0.91 to 1.08
Estimation Comments [Not Specified]
13.Other Pre-specified Outcome
Title Net Clinical Benefit (Composite of All-cause Mortality/MI/Ischemic Stroke/ALI/Major Amputation/TIMI Major Bleeding)
Hide Description Participants with all-cause death, MI, ischemic stroke, ALI, major amputation or Thrombolysis in Myocardial Infarction (TIMI) major bleeding. If no event, censoring occurs at the minimum of (PACD, last endpoint assessment date)
Time Frame From randomization to PACD, an average of 2.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
The population was the full analysis set, which included all randomized patients
Arm/Group Title Ticagrelor 90 mg bd Clopidogrel 75 mg od
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 6930 6955
Measure Type: Number
Unit of Measure: Participant
1183 1199
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ticagrelor 90 mg bd, Clopidogrel 75 mg od
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.949
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.00
Confidence Interval (2-Sided) 95%
0.92 to 1.08
Estimation Comments [Not Specified]
14.Other Pre-specified Outcome
Title Non-CV Death
Hide Description Participants with non-CV death. If no event, censoring occurs at the minimum of (PACD, last endpoint assessment date, CV death)
Time Frame From randomization to PACD, an average of 2.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
The population was the full analysis set, which included all randomized patients
Arm/Group Title Ticagrelor 90 mg bd Clopidogrel 75 mg od
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 6930 6955
Measure Type: Number
Unit of Measure: Participant
250 272
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ticagrelor 90 mg bd, Clopidogrel 75 mg od
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.377
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.93
Confidence Interval (2-Sided) 95%
0.78 to 1.10
Estimation Comments [Not Specified]
15.Other Pre-specified Outcome
Title Changes in Fontaine Stage
Hide Description

Progression of the clinical/symptomatic status of the limb by changes in Fontaine stage.

Stage I – Asymptomatic Stage IIa – Intermittent claudication after more than 200 meters of pain free walking Stage IIb – Intermittent claudication after less than 200 meters of walking Stage III – Rest pain Stage IV – Ischemic ulcers or gangrene

Time Frame From randomization to PACD, an average of 2.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
The population was the full analysis set, which included all randomized patients
Arm/Group Title Ticagrelor - Stage I Ticagrelor - Stage IIa Ticagrelor - Stage IIb Ticagrelor - Stage III Ticagrelor - Stage IV Clopidogrel - Stage I Clopidogrel - Stage IIa Clopidogrel - Stage IIb Clopidogrel - Stage III Clopidogrel - Stage IV
Hide Arm/Group Description:
Baseline Fontaine stage I
Baseline Fontaine stage IIa
Baseline Fontaine stage IIb
Baseline Fontaine stage III
Baseline Fontaine stage IV
Baseline Fontaine stage I
Baseline Fontaine stage IIa
Baseline Fontaine stage IIb
Baseline Fontaine stage III
Baseline Fontaine stage IV
Overall Number of Participants Analyzed 1309 3674 1620 186 140 1292 3736 1608 192 125
Measure Type: Number
Unit of Measure: Participant
Stage I - End of treatment 775 683 171 15 26 743 723 198 33 19
Stage IIa - End of treatment 227 1948 560 41 28 230 1956 557 33 21
Stage IIb - End of treatment 45 269 469 39 19 56 311 450 38 15
Stage III - End of treatment 7 24 12 31 7 9 15 23 23 12
Stage IV - End of treatment 7 7 5 1 13 4 7 10 5 13
Missing - End of treatment 248 743 403 59 47 250 724 370 60 45
16.Other Pre-specified Outcome
Title Changes in Rutherford Classification
Hide Description

Progression of the clinical/symptomatic status of the limb by changes in Rutherford classification.

Category 0 – Asymptomatic Category 1 – Mild claudication Category 2 – Moderate claudication – The distance that delineates mild, moderate and severe claudication is not specified in the Rutherford classification, but is mentioned in the Fontaine classification as 200 meters.

Category 3 – Severe claudication Category 4 – Rest pain Category 5 – Ischemic ulceration not exceeding ulcer of the digits of the foot Category 6 – Severe ischemic ulcers or frank gangrene

Time Frame From randomization to PACD, an average of 2.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
The population was the full analysis set, which included all randomized patients
Arm/Group Title Ticagrelor - Cat 0 Ticagrelor - Stage II Ticagrelor - Cat 3 Ticagrelor - Cat 4 Ticagrelor - Cat 5 Ticagrelor - Cat 6 Clopidogrel - Cat 0 Clopidogrel - Cat 1/2 Clopidogrel - Cat 3 Clopidogrel - Cat 4 Clopidogrel - Cat 5 Clopidogrel - Cat 6
Hide Arm/Group Description:
Baseline Rutherford category 0
Baseline Rutherford category 1/2
Baseline Rutherford category 3
Baseline Rutherford category 4
Baseline Rutherford category 5
Baseline Rutherford category 6
Baseline Rutherford category 0
Baseline Rutherford category 1/2
Baseline Rutherford category 3
Baseline Rutherford category 4
Baseline Rutherford category 5
Baseline Rutherford category 6
Overall Number of Participants Analyzed 1309 3674 1620 186 107 33 1292 3736 1608 192 100 25
Measure Type: Number
Unit of Measure: Participant
Category 0 - End of treatment 775 683 171 15 23 3 743 723 198 33 13 6
Category 1/2 - End of treatment 227 1948 560 41 23 5 230 1956 557 33 18 3
Category 3 - End of treatment 45 269 469 39 13 6 56 311 450 38 12 3
Category 4 - End of treatment 7 24 12 31 4 3 9 15 23 23 11 1
Category 5 - End of treatment 5 4 3 1 11 0 2 6 6 4 12 1
Category 6 - End of treatment 2 3 2 0 0 2 2 1 4 1 0 0
Missing - End of treatment 248 743 403 59 33 14 250 724 370 60 34 11
17.Other Pre-specified Outcome
Title Change in ABI/TBI From Baseline
Hide Description

Change in ankle brachial index (ABI) / toe brachial index (TBI).

Ankle brachial index (ABI) is the ratio of blood pressures from the ankle and arm and is used for diagnosing peripheral arterial occlusive disease (PAOD):

Normal: 1 to 1.29 Borderline: 0.91 to 0.99 Mild PAOD: 0.71 to 0.90 Medium severe PAOD: 0.41 to 0.7 Severe PAOD: <0.4

Toe brachial index (TBI) is the ratio between the toe pressure and the higher brachial pressure, used for diagnosing PAOD when the ABI cannot be used:

Normal: >0.7 Mild: 0.5-0.7 Moderate: 0.35-0.5 Moderate-Severe: <0.35 and toe pressure 40 mmHg Severe: <0.35 and toe pressure < 30 mmHg

Time Frame From randomization to PACD, an average of 2.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
The population was the full analysis set, which included all randomized patients
Arm/Group Title Ticagrelor 90 mg bd Clopidogrel 75 mg od
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 6908 6940
Mean (Standard Deviation)
Unit of Measure: Change in ABI/TBI
ABI - 6 months N = 6184(Tica), 6319(Clopi) 0.016  (0.136) 0.011  (0.134)
ABI - End of treatment N = 4951(Tica), 5073(Clopi) 0.022  (0.167) 0.016  (0.167)
TBI - 6 months N = 55(Tica), 48(Clopi) 0.050  (0.132) 0.036  (0.137)
TBI - End of treatment N = 36(Tica), 21(Clopi) 0.059  (0.115) -0.065  (0.304)
18.Other Pre-specified Outcome
Title Any Amputation Caused by PAD
Hide Description Participants with any amputation caused by peripheral arterial disease (PAD). If no event, censoring occurs at the minimum of (PACD, last endpoint assessment date, death date)
Time Frame From randomization to PACD, an average of 2.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
The population was the full analysis set, which included all randomized patients
Arm/Group Title Ticagrelor 90 mg bd Clopidogrel 75 mg od
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 6930 6955
Measure Type: Number
Unit of Measure: Participant
179 208
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ticagrelor 90 mg bd, Clopidogrel 75 mg od
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.164
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.87
Confidence Interval (2-Sided) 95%
0.71 to 1.06
Estimation Comments [Not Specified]
19.Other Pre-specified Outcome
Title Major Amputation Caused by PAD
Hide Description Participants with major amputation caused by PAD. If no event, censoring occurs at the minimum of (PACD, last endpoint assessment date, death date)
Time Frame From randomization to PACD, an average of 2.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
The population was the full analysis set, which included all randomized patients
Arm/Group Title Ticagrelor 90 mg bd Clopidogrel 75 mg od
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 6930 6955
Measure Type: Number
Unit of Measure: Participant
100 116
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ticagrelor 90 mg bd, Clopidogrel 75 mg od
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.306
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.87
Confidence Interval (2-Sided) 95%
0.67 to 1.14
Estimation Comments [Not Specified]
20.Other Pre-specified Outcome
Title CV-related Hospitalization
Hide Description Participants with hospitalization associated with CV death, hospitalization due to MI, ischemic stroke, lower extremity revascularization, major amputation due to PAD, transient ischemic attack (TIA), coronary revascularization or unstable angina. If no event, censoring occurs at the minimum of (PACD, last endpoint assessment date, death date)
Time Frame From randomization to PACD, an average of 2.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
The population was the full analysis set, which included all randomized patients
Arm/Group Title Ticagrelor 90 mg bd Clopidogrel 75 mg od
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 6930 6955
Measure Type: Number
Unit of Measure: Participant
1312 1314
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ticagrelor 90 mg bd, Clopidogrel 75 mg od
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.887
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.01
Confidence Interval (2-Sided) 95%
0.93 to 1.09
Estimation Comments [Not Specified]
21.Other Pre-specified Outcome
Title TIMI Major Bleeding Events
Hide Description Participants with TIMI major bleeding event. If no event, censoring occurs at the minimum of (last endpoint assessment date, death date, 7 days after last dose of study drug)
Time Frame From the date of first dose and up to and including 7 days following the date of last dose of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
The population was the safety analysis set, which included all patients who received at least 1 dose of randomized ticagrelor or clopidogrel and for whom post-dose data are available
Arm/Group Title Ticagrelor 90 mg bd Clopidogrel 75 mg od
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 6910 6932
Measure Type: Number
Unit of Measure: Participant
113 109
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ticagrelor 90 mg bd, Clopidogrel 75 mg od
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.489
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.10
Confidence Interval (2-Sided) 95%
0.84 to 1.43
Estimation Comments [Not Specified]
22.Other Pre-specified Outcome
Title TIMI Major or Minor Bleeding Events
Hide Description Participants with TIMI major or minor bleeding event. If no event, censoring occurs at the minimum of (last endpoint assessment date, death date, 7 days after last dose of study drug)
Time Frame From the date of first dose and up to and including 7 days following the date of last dose of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
The population was the safety analysis set, which included all patients who received at least 1 dose of randomized ticagrelor or clopidogrel and for whom post-dose data are available
Arm/Group Title Ticagrelor 90 mg bd Clopidogrel 75 mg od
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 6910 6932
Measure Type: Number
Unit of Measure: Participant
193 175
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ticagrelor 90 mg bd, Clopidogrel 75 mg od
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.138
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.17
Confidence Interval (2-Sided) 95%
0.95 to 1.43
Estimation Comments [Not Specified]
23.Other Pre-specified Outcome
Title PLATO Major Bleeding Events
Hide Description Participants with PLATO major bleeding event. If no event, censoring occurs at the minimum of (last endpoint assessment date, death date, 7 days after last dose of study drug)
Time Frame From the date of first dose and up to and including 7 days following the date of last dose of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
The population was the safety analysis set, which included all patients who received at least 1 dose of randomized ticagrelor or clopidogrel and for whom post-dose data are available
Arm/Group Title Ticagrelor 90 mg bd Clopidogrel 75 mg od
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 6910 6932
Measure Type: Number
Unit of Measure: Participant
206 188
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ticagrelor 90 mg bd, Clopidogrel 75 mg od
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.139
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.16
Confidence Interval (2-Sided) 95%
0.95 to 1.41
Estimation Comments [Not Specified]
24.Other Pre-specified Outcome
Title Premature Permanent Discontinuation of Study Drug Due to Any Bleeding Event
Hide Description Participants with a permanent discontinuation of study drug due to any bleeding event. If no event, censoring occurs at the minimum of (last endpoint assessment date, death date, 7 days after last dose of study drug)
Time Frame From the date of first dose and up to and including 7 days following the date of last dose of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
The population was the saftey analysis set, which included all patients who received at least 1 dose of randomized ticagrelor or clopidogrel and for whom post-dose data are available
Arm/Group Title Ticagrelor 90 mg bd Clopidogrel 75 mg od
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 6910 6932
Measure Type: Number
Unit of Measure: Participant
168 112
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ticagrelor 90 mg bd, Clopidogrel 75 mg od
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.58
Confidence Interval (2-Sided) 95%
1.24 to 2.00
Estimation Comments [Not Specified]
Time Frame On or after the date of first dose and up to and including 7 days following the date of last dose of study medication
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Clopidogrel 75mg od Ticagrelor 90mg bd
Hide Arm/Group Description [Not Specified] [Not Specified]
All-Cause Mortality
Clopidogrel 75mg od Ticagrelor 90mg bd
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Clopidogrel 75mg od Ticagrelor 90mg bd
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1788/6932 (25.79%)      1716/6910 (24.83%)    
Blood and lymphatic system disorders     
Anaemia  1  38/6932 (0.55%)  40 39/6910 (0.56%)  43
Anaemia macrocytic  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Anaemia of chronic disease  1  1/6932 (0.01%)  4 0/6910 (0.00%)  0
Aplastic anaemia  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Autoimmune aplastic anaemia  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Febrile neutropenia  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Haemolytic uraemic syndrome  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Haemorrhagic anaemia  1  2/6932 (0.03%)  2 0/6910 (0.00%)  0
Hypochromic anaemia  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Iron deficiency anaemia  1  4/6932 (0.06%)  4 6/6910 (0.09%)  6
Leukocytosis  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Lymphadenitis  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Lymphadenopathy  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Microcytic anaemia  1  2/6932 (0.03%)  2 3/6910 (0.04%)  3
Neutropenia  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Normochromic normocytic anaemia  1  1/6932 (0.01%)  1 1/6910 (0.01%)  1
Pancytopenia  1  0/6932 (0.00%)  0 3/6910 (0.04%)  3
Thrombocytopenia  1  1/6932 (0.01%)  1 3/6910 (0.04%)  3
Cardiac disorders     
Angina pectoris  1  18/6932 (0.26%)  20 32/6910 (0.46%)  34
Angina unstable  1  6/6932 (0.09%)  8 10/6910 (0.14%)  11
Aortic valve disease  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Aortic valve incompetence  1  1/6932 (0.01%)  1 2/6910 (0.03%)  2
Aortic valve stenosis  1  8/6932 (0.12%)  8 3/6910 (0.04%)  3
Arrhythmia  1  1/6932 (0.01%)  1 1/6910 (0.01%)  1
Arrhythmia supraventricular  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Arteriosclerosis coronary artery  1  2/6932 (0.03%)  2 0/6910 (0.00%)  0
Arteriospasm coronary  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Atrial fibrillation  1  67/6932 (0.97%)  69 69/6910 (1.00%)  69
Atrial flutter  1  6/6932 (0.09%)  6 11/6910 (0.16%)  12
Atrial tachycardia  1  4/6932 (0.06%)  4 0/6910 (0.00%)  0
Atrioventricular block  1  0/6932 (0.00%)  0 2/6910 (0.03%)  2
Atrioventricular block complete  1  4/6932 (0.06%)  4 6/6910 (0.09%)  6
Atrioventricular block first degree  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Atrioventricular block second degree  1  2/6932 (0.03%)  2 5/6910 (0.07%)  5
Bradyarrhythmia  1  4/6932 (0.06%)  4 9/6910 (0.13%)  9
Bradycardia  1  8/6932 (0.12%)  8 4/6910 (0.06%)  4
Bundle branch block left  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Cardiac arrest  1  3/6932 (0.04%)  3 2/6910 (0.03%)  2
Cardiac failure  1  23/6932 (0.33%)  29 28/6910 (0.41%)  30
Cardiac failure acute  1  3/6932 (0.04%)  3 4/6910 (0.06%)  4
Cardiac failure chronic  1  6/6932 (0.09%)  6 6/6910 (0.09%)  7
Cardiac failure congestive  1  88/6932 (1.27%)  108 68/6910 (0.98%)  81
Cardiac tamponade  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Cardiac ventricular thrombosis  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Cardio-respiratory arrest  1  1/6932 (0.01%)  2 0/6910 (0.00%)  0
Cardiogenic shock  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Cardiomyopathy  1  3/6932 (0.04%)  3 1/6910 (0.01%)  1
Cardiopulmonary failure  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Cardiovascular insufficiency  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Chronic left ventricular failure  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Congestive cardiomyopathy  1  0/6932 (0.00%)  0 3/6910 (0.04%)  3
Coronary artery disease  1  4/6932 (0.06%)  4 8/6910 (0.12%)  8
Coronary artery dissection  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Heart valve stenosis  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Hypertensive heart disease  1  0/6932 (0.00%)  0 3/6910 (0.04%)  3
Ischaemic cardiomyopathy  1  4/6932 (0.06%)  4 0/6910 (0.00%)  0
Left ventricular dysfunction  1  2/6932 (0.03%)  2 1/6910 (0.01%)  1
Left ventricular failure  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Mitral valve incompetence  1  5/6932 (0.07%)  5 0/6910 (0.00%)  0
Myocardial infarction  1  2/6932 (0.03%)  2 2/6910 (0.03%)  2
Myocardial ischaemia  1  1/6932 (0.01%)  1 1/6910 (0.01%)  1
Nodal arrhythmia  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Palpitations  1  1/6932 (0.01%)  1 1/6910 (0.01%)  1
Pericardial effusion  1  2/6932 (0.03%)  2 1/6910 (0.01%)  1
Sinus bradycardia  1  2/6932 (0.03%)  2 1/6910 (0.01%)  1
Sinus node dysfunction  1  5/6932 (0.07%)  5 2/6910 (0.03%)  2
Sinus tachycardia  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Stress cardiomyopathy  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Supraventricular extrasystoles  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Supraventricular tachycardia  1  4/6932 (0.06%)  5 4/6910 (0.06%)  6
Tachyarrhythmia  1  3/6932 (0.04%)  3 1/6910 (0.01%)  1
Tachycardia  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Tachycardia paroxysmal  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Tricuspid valve incompetence  1  2/6932 (0.03%)  2 0/6910 (0.00%)  0
Ventricular arrhythmia  1  3/6932 (0.04%)  3 3/6910 (0.04%)  3
Ventricular extrasystoles  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Ventricular fibrillation  1  3/6932 (0.04%)  3 0/6910 (0.00%)  0
Ventricular hypokinesia  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Ventricular tachyarrhythmia  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Ventricular tachycardia  1  5/6932 (0.07%)  5 10/6910 (0.14%)  12
Congenital, familial and genetic disorders     
Arteriovenous malformation  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Corneal dystrophy  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Hydrocele  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Hypertrophic cardiomyopathy  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Phimosis  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Ear and labyrinth disorders     
Acute vestibular syndrome  1  3/6932 (0.04%)  3 0/6910 (0.00%)  0
Deafness  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Hypoacusis  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Meniere's disease  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Middle ear effusion  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Sudden hearing loss  1  2/6932 (0.03%)  2 1/6910 (0.01%)  1
Tinnitus  1  1/6932 (0.01%)  1 1/6910 (0.01%)  1
Vertigo  1  7/6932 (0.10%)  7 9/6910 (0.13%)  9
Vertigo positional  1  2/6932 (0.03%)  2 2/6910 (0.03%)  2
Vestibular disorder  1  2/6932 (0.03%)  2 0/6910 (0.00%)  0
Endocrine disorders     
Adrenal insufficiency  1  0/6932 (0.00%)  0 2/6910 (0.03%)  2
Goitre  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Hyperthyroidism  1  1/6932 (0.01%)  1 4/6910 (0.06%)  4
Hypothyroidism  1  1/6932 (0.01%)  1 1/6910 (0.01%)  1
Inappropriate antidiuretic hormone secretion  1  1/6932 (0.01%)  1 1/6910 (0.01%)  1
Thyroid cyst  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Thyroid mass  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Thyroiditis  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Eye disorders     
Angle closure glaucoma  1  1/6932 (0.01%)  1 1/6910 (0.01%)  1
Cataract  1  14/6932 (0.20%)  17 14/6910 (0.20%)  15
Conjunctival haemorrhage  1  1/6932 (0.01%)  1 1/6910 (0.01%)  1
Diabetic retinopathy  1  3/6932 (0.04%)  3 0/6910 (0.00%)  0
Exophthalmos  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Eye haemorrhage  1  4/6932 (0.06%)  4 2/6910 (0.03%)  3
Macular hole  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Open angle glaucoma  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Optic ischaemic neuropathy  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Optic neuropathy  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Retinal artery embolism  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Retinal degeneration  1  1/6932 (0.01%)  1 1/6910 (0.01%)  1
Retinal detachment  1  6/6932 (0.09%)  6 1/6910 (0.01%)  1
Retinal haemorrhage  1  2/6932 (0.03%)  3 1/6910 (0.01%)  1
Retinal vein occlusion  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Retinoschisis  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Uveitis  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Vision blurred  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Vitreous haemorrhage  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Gastrointestinal disorders     
Abdominal adhesions  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Abdominal discomfort  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Abdominal hernia  1  1/6932 (0.01%)  1 4/6910 (0.06%)  4
Abdominal pain  1  9/6932 (0.13%)  9 8/6910 (0.12%)  10
Abdominal pain upper  1  3/6932 (0.04%)  3 8/6910 (0.12%)  8
Abdominal wall haematoma  1  1/6932 (0.01%)  1 1/6910 (0.01%)  1
Acid peptic disease  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Acute abdomen  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Alcoholic pancreatitis  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Anal fistula  1  1/6932 (0.01%)  1 1/6910 (0.01%)  1
Anal haemorrhage  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Anal incontinence  1  1/6932 (0.01%)  1 1/6910 (0.01%)  1
Ascites  1  1/6932 (0.01%)  2 0/6910 (0.00%)  0
Barrett's oesophagus  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Chronic gastritis  1  1/6932 (0.01%)  1 1/6910 (0.01%)  1
Colitis  1  4/6932 (0.06%)  4 2/6910 (0.03%)  2
Colitis ischaemic  1  1/6932 (0.01%)  1 6/6910 (0.09%)  6
Constipation  1  2/6932 (0.03%)  2 1/6910 (0.01%)  1
Diarrhoea  1  4/6932 (0.06%)  4 5/6910 (0.07%)  5
Diverticulum  1  1/6932 (0.01%)  1 1/6910 (0.01%)  1
Diverticulum intestinal  1  1/6932 (0.01%)  1 2/6910 (0.03%)  2
Diverticulum intestinal haemorrhagic  1  3/6932 (0.04%)  3 5/6910 (0.07%)  5
Duodenal polyp  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Duodenal ulcer  1  1/6932 (0.01%)  1 3/6910 (0.04%)  3
Duodenal ulcer haemorrhage  1  3/6932 (0.04%)  3 1/6910 (0.01%)  1
Duodenitis  1  1/6932 (0.01%)  1 2/6910 (0.03%)  2
Dyspepsia  1  2/6932 (0.03%)  2 2/6910 (0.03%)  2
Dysphagia  1  4/6932 (0.06%)  4 2/6910 (0.03%)  2
Enteritis  1  1/6932 (0.01%)  1 1/6910 (0.01%)  1
Enterocolitis  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Enterocolitis haemorrhagic  1  1/6932 (0.01%)  1 1/6910 (0.01%)  1
Epigastric discomfort  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Erosive duodenitis  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Erosive oesophagitis  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Food poisoning  1  1/6932 (0.01%)  1 2/6910 (0.03%)  2
Gastric disorder  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Gastric haemorrhage  1  3/6932 (0.04%)  3 3/6910 (0.04%)  3
Gastric polyps  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Gastric ulcer  1  4/6932 (0.06%)  4 2/6910 (0.03%)  2
Gastric ulcer haemorrhage  1  5/6932 (0.07%)  5 6/6910 (0.09%)  6
Gastric ulcer perforation  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Gastritis  1  10/6932 (0.14%)  10 8/6910 (0.12%)  12
Gastritis alcoholic  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Gastritis erosive  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Gastritis haemorrhagic  1  1/6932 (0.01%)  2 1/6910 (0.01%)  1
Gastroduodenal ulcer  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Gastrointestinal angiodysplasia  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Gastrointestinal angiodysplasia haemorrhagic  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Gastrointestinal disorder  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Gastrointestinal haemorrhage  1  38/6932 (0.55%)  41 34/6910 (0.49%)  39
Gastrointestinal inflammation  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Gastrointestinal obstruction  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Gastrointestinal pain  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Gastrointestinal polyp haemorrhage  1  0/6932 (0.00%)  0 2/6910 (0.03%)  2
Gastrointestinal ulcer haemorrhage  1  0/6932 (0.00%)  0 2/6910 (0.03%)  2
Gastrooesophageal reflux disease  1  6/6932 (0.09%)  6 4/6910 (0.06%)  4
Haematemesis  1  1/6932 (0.01%)  1 1/6910 (0.01%)  1
Haemorrhagic erosive gastritis  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Haemorrhoidal haemorrhage  1  2/6932 (0.03%)  2 3/6910 (0.04%)  3
Haemorrhoids  1  3/6932 (0.04%)  3 1/6910 (0.01%)  1
Haemorrhoids thrombosed  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Hiatus hernia  1  1/6932 (0.01%)  1 2/6910 (0.03%)  2
Hypoaesthesia oral  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Ileus  1  3/6932 (0.04%)  3 10/6910 (0.14%)  11
Ileus paralytic  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Impaired gastric emptying  1  1/6932 (0.01%)  1 2/6910 (0.03%)  2
Incarcerated inguinal hernia  1  3/6932 (0.04%)  3 0/6910 (0.00%)  0
Incarcerated umbilical hernia  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Inguinal hernia  1  22/6932 (0.32%)  23 20/6910 (0.29%)  21
Inguinal hernia strangulated  1  1/6932 (0.01%)  1 1/6910 (0.01%)  1
Intestinal haemorrhage  1  1/6932 (0.01%)  1 1/6910 (0.01%)  1
Intestinal infarction  1  1/6932 (0.01%)  1 1/6910 (0.01%)  1
Intestinal ischaemia  1  2/6932 (0.03%)  2 1/6910 (0.01%)  1
Intestinal obstruction  1  2/6932 (0.03%)  2 1/6910 (0.01%)  1
Intestinal perforation  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Intestinal polyp  1  0/6932 (0.00%)  0 2/6910 (0.03%)  2
Intra-abdominal haematoma  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Irritable bowel syndrome  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Large intestinal haemorrhage  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Large intestinal ulcer haemorrhage  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Large intestine perforation  1  2/6932 (0.03%)  2 1/6910 (0.01%)  1
Large intestine polyp  1  15/6932 (0.22%)  16 14/6910 (0.20%)  15
Lower gastrointestinal haemorrhage  1  2/6932 (0.03%)  2 5/6910 (0.07%)  5
Mallory-Weiss syndrome  1  1/6932 (0.01%)  1 2/6910 (0.03%)  2
Mechanical ileus  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Melaena  1  1/6932 (0.01%)  1 1/6910 (0.01%)  1
Mesenteric artery stenosis  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Mesenteric artery thrombosis  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Mesenteric panniculitis  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Mesenteric vein thrombosis  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Mouth haemorrhage  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Nausea  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Oedematous pancreatitis  1  1/6932 (0.01%)  1 1/6910 (0.01%)  1
Oesophageal achalasia  1  0/6932 (0.00%)  0 2/6910 (0.03%)  3
Oesophageal fistula  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Oesophageal spasm  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Oesophageal ulcer  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Oesophageal ulcer haemorrhage  1  0/6932 (0.00%)  0 2/6910 (0.03%)  2
Oesophagitis  1  1/6932 (0.01%)  1 1/6910 (0.01%)  1
Oesophagitis haemorrhagic  1  1/6932 (0.01%)  1 1/6910 (0.01%)  1
Oesophagitis ulcerative  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Pancreatic cyst  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Pancreatic mass  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Pancreatic pseudocyst  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Pancreatitis  1  8/6932 (0.12%)  8 8/6910 (0.12%)  8
Pancreatitis acute  1  9/6932 (0.13%)  12 4/6910 (0.06%)  4
Pancreatitis chronic  1  0/6932 (0.00%)  0 2/6910 (0.03%)  2
Pancreatitis relapsing  1  1/6932 (0.01%)  3 1/6910 (0.01%)  1
Peptic ulcer  1  1/6932 (0.01%)  1 1/6910 (0.01%)  1
Peptic ulcer haemorrhage  1  2/6932 (0.03%)  2 0/6910 (0.00%)  0
Periodontal disease  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Peritoneal haemorrhage  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Proctitis  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Rectal haemorrhage  1  6/6932 (0.09%)  7 1/6910 (0.01%)  1
Rectal polyp  1  2/6932 (0.03%)  2 2/6910 (0.03%)  2
Reflux gastritis  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Retroperitoneal haematoma  1  1/6932 (0.01%)  1 1/6910 (0.01%)  1
Retroperitoneal haemorrhage  1  3/6932 (0.04%)  3 2/6910 (0.03%)  2
Small intestinal haemorrhage  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Small intestinal obstruction  1  4/6932 (0.06%)  4 1/6910 (0.01%)  1
Small intestinal perforation  1  0/6932 (0.00%)  0 2/6910 (0.03%)  2
Small intestinal stenosis  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Strangulated umbilical hernia  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Subileus  1  2/6932 (0.03%)  2 2/6910 (0.03%)  2
Tongue dysplasia  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Umbilical hernia  1  2/6932 (0.03%)  2 2/6910 (0.03%)  2
Upper gastrointestinal haemorrhage  1  7/6932 (0.10%)  7 9/6910 (0.13%)  9
Volvulus  1  1/6932 (0.01%)  3 0/6910 (0.00%)  0
Vomiting  1  1/6932 (0.01%)  1 3/6910 (0.04%)  3
General disorders     
Asthenia  1  3/6932 (0.04%)  3 3/6910 (0.04%)  4
Chest discomfort  1  2/6932 (0.03%)  2 1/6910 (0.01%)  1
Chest pain  1  7/6932 (0.10%)  8 9/6910 (0.13%)  9
Complication associated with device  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Complication of device removal  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Cyst  1  1/6932 (0.01%)  1 1/6910 (0.01%)  1
Death  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Drowning  1  2/6932 (0.03%)  2 0/6910 (0.00%)  0
Face oedema  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Fatigue  1  0/6932 (0.00%)  0 2/6910 (0.03%)  2
Gait disturbance  1  1/6932 (0.01%)  1 1/6910 (0.01%)  1
General physical health deterioration  1  0/6932 (0.00%)  0 2/6910 (0.03%)  2
Generalised oedema  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Impaired healing  1  3/6932 (0.04%)  3 0/6910 (0.00%)  0
Medical device site erosion  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Multiple organ dysfunction syndrome  1  5/6932 (0.07%)  5 6/6910 (0.09%)  6
Non-cardiac chest pain  1  37/6932 (0.53%)  38 37/6910 (0.54%)  40
Oedema peripheral  1  2/6932 (0.03%)  2 1/6910 (0.01%)  1
Pain  1  0/6932 (0.00%)  0 2/6910 (0.03%)  2
Puncture site haemorrhage  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Pyrexia  1  2/6932 (0.03%)  2 5/6910 (0.07%)  5
Soft tissue inflammation  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Strangulated hernia  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Systemic inflammatory response syndrome  1  1/6932 (0.01%)  1 1/6910 (0.01%)  1
Vascular stent occlusion  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Vascular stent restenosis  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Vascular stent stenosis  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Vascular stent thrombosis  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Vessel puncture site haematoma  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Hepatobiliary disorders     
Alcoholic liver disease  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Autoimmune hepatitis  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Bile duct obstruction  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Bile duct stenosis  1  3/6932 (0.04%)  3 0/6910 (0.00%)  0
Bile duct stone  1  3/6932 (0.04%)  3 1/6910 (0.01%)  1
Biliary dyskinesia  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Cholangiolitis  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Cholangitis  1  3/6932 (0.04%)  4 1/6910 (0.01%)  1
Cholangitis acute  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Cholecystitis  1  8/6932 (0.12%)  9 14/6910 (0.20%)  14
Cholecystitis acute  1  10/6932 (0.14%)  10 11/6910 (0.16%)  11
Cholecystitis chronic  1  1/6932 (0.01%)  1 2/6910 (0.03%)  2
Cholelithiasis  1  13/6932 (0.19%)  13 14/6910 (0.20%)  16
Cholestasis  1  1/6932 (0.01%)  1 1/6910 (0.01%)  1
Cirrhosis alcoholic  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Fatty liver alcoholic  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Gallbladder perforation  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Hepatic cirrhosis  1  2/6932 (0.03%)  2 5/6910 (0.07%)  5
Hepatic cyst  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Hepatic haematoma  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Hepatitis  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Hepatitis acute  1  1/6932 (0.01%)  1 1/6910 (0.01%)  1
Hepatitis alcoholic  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Jaundice cholestatic  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Liver injury  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Immune system disorders     
Allergy to arthropod sting  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Allergy to chemicals  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Anaphylactic reaction  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Anaphylactic shock  1  1/6932 (0.01%)  1 1/6910 (0.01%)  1
Drug hypersensitivity  1  1/6932 (0.01%)  2 1/6910 (0.01%)  1
Hypersensitivity  1  2/6932 (0.03%)  2 2/6910 (0.03%)  2
Overlap syndrome  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Infections and infestations     
Abdominal abscess  1  1/6932 (0.01%)  1 1/6910 (0.01%)  1
Abdominal infection  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Abdominal wall abscess  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Abscess intestinal  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Abscess jaw  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Abscess limb  1  2/6932 (0.03%)  2 1/6910 (0.01%)  1
Abscess of salivary gland  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Acute hepatitis B  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Anal abscess  1  2/6932 (0.03%)  2 3/6910 (0.04%)  3
Appendicitis  1  9/6932 (0.13%)  9 5/6910 (0.07%)  5
Appendicitis perforated  1  2/6932 (0.03%)  2 2/6910 (0.03%)  2
Arteriovenous graft site infection  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Arthritis bacterial  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Atypical mycobacterial pneumonia  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Bacteraemia  1  0/6932 (0.00%)  0 4/6910 (0.06%)  4
Bacterial infection  1  1/6932 (0.01%)  1 1/6910 (0.01%)  1
Biliary tract infection  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Bone abscess  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Bronchitis  1  19/6932 (0.27%)  19 23/6910 (0.33%)  24
Campylobacter gastroenteritis  1  1/6932 (0.01%)  1 1/6910 (0.01%)  1
Carbuncle  1  2/6932 (0.03%)  2 0/6910 (0.00%)  0
Cellulitis  1  26/6932 (0.38%)  28 27/6910 (0.39%)  28
Cholangitis infective  1  1/6932 (0.01%)  1 1/6910 (0.01%)  1
Cholecystitis infective  1  2/6932 (0.03%)  2 2/6910 (0.03%)  2
Chronic hepatitis C  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Chronic sinusitis  1  3/6932 (0.04%)  3 0/6910 (0.00%)  0
Clostridium difficile colitis  1  8/6932 (0.12%)  8 4/6910 (0.06%)  4
Clostridium difficile infection  1  2/6932 (0.03%)  2 3/6910 (0.04%)  3
Colonic abscess  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Corynebacterium bacteraemia  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Cystitis  1  0/6932 (0.00%)  0 3/6910 (0.04%)  3
Device related infection  1  6/6932 (0.09%)  6 5/6910 (0.07%)  5
Diabetic foot infection  1  2/6932 (0.03%)  3 2/6910 (0.03%)  2
Diabetic gangrene  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Diarrhoea infectious  1  1/6932 (0.01%)  1 1/6910 (0.01%)  1
Diverticulitis  1  7/6932 (0.10%)  7 6/6910 (0.09%)  6
Diverticulitis intestinal haemorrhagic  1  3/6932 (0.04%)  3 1/6910 (0.01%)  1
Echinococciasis  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Emphysematous cholecystitis  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Empyema  1  2/6932 (0.03%)  2 1/6910 (0.01%)  1
Encephalitis  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Endocarditis  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Endocarditis enterococcal  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Epididymitis  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Epiglottitis  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Erysipelas  1  4/6932 (0.06%)  4 5/6910 (0.07%)  5
Escherichia bacteraemia  1  0/6932 (0.00%)  0 2/6910 (0.03%)  2
Escherichia infection  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Escherichia sepsis  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Escherichia urinary tract infection  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Gallbladder abscess  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Gallbladder empyema  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Gangrene  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Gastroenteritis  1  13/6932 (0.19%)  13 12/6910 (0.17%)  13
Gastroenteritis salmonella  1  2/6932 (0.03%)  2 0/6910 (0.00%)  0
Gastroenteritis viral  1  2/6932 (0.03%)  2 0/6910 (0.00%)  0
Graft infection  1  3/6932 (0.04%)  3 5/6910 (0.07%)  5
Groin abscess  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Groin infection  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Haematoma infection  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Herpes virus infection  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Herpes zoster  1  3/6932 (0.04%)  3 2/6910 (0.03%)  2
Impetigo  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Implant site infection  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Incision site infection  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Infected dermal cyst  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Infected seroma  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Infected skin ulcer  1  1/6932 (0.01%)  1 1/6910 (0.01%)  1
Infectious colitis  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Infective exacerbation of chronic obstructive airways disease  1  2/6932 (0.03%)  2 1/6910 (0.01%)  1
Influenza  1  6/6932 (0.09%)  6 8/6910 (0.12%)  8
Intervertebral discitis  1  1/6932 (0.01%)  1 1/6910 (0.01%)  1
Kidney infection  1  0/6932 (0.00%)  0 2/6910 (0.03%)  2
Klebsiella sepsis  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Laryngitis  1  1/6932 (0.01%)  1 3/6910 (0.04%)  5
Liver abscess  1  0/6932 (0.00%)  0 2/6910 (0.03%)  2
Localised infection  1  0/6932 (0.00%)  0 2/6910 (0.03%)  2
Lower respiratory tract infection  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Lung abscess  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Lung infection  1  2/6932 (0.03%)  2 7/6910 (0.10%)  7
Lymphangitis  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Mediastinitis  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Medical device site infection  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Meningitis tuberculous  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Muscle abscess  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Mycobacterium avium complex infection  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Nasopharyngitis  1  0/6932 (0.00%)  0 2/6910 (0.03%)  3
Necrotising fasciitis  1  1/6932 (0.01%)  1 2/6910 (0.03%)  2
Oesophageal candidiasis  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Ophthalmic herpes zoster  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Orchitis  1  2/6932 (0.03%)  2 0/6910 (0.00%)  0
Oropharyngeal candidiasis  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Osteomyelitis  1  9/6932 (0.13%)  10 7/6910 (0.10%)  7
Osteomyelitis chronic  1  2/6932 (0.03%)  2 0/6910 (0.00%)  0
Paronychia  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Periodontitis  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Peritonitis  1  6/6932 (0.09%)  6 0/6910 (0.00%)  0
Pneumocystis jirovecii pneumonia  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Pneumonia  1  164/6932 (2.37%)  175 137/6910 (1.98%)  141
Pneumonia bacterial  1  1/6932 (0.01%)  1 6/6910 (0.09%)  6
Pneumonia influenzal  1  0/6932 (0.00%)  0 2/6910 (0.03%)  2
Pneumonia klebsiella  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Pneumonia pneumococcal  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Post procedural cellulitis  1  1/6932 (0.01%)  3 0/6910 (0.00%)  0
Post procedural infection  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Postoperative abscess  1  2/6932 (0.03%)  2 0/6910 (0.00%)  0
Postoperative wound infection  1  10/6932 (0.14%)  10 4/6910 (0.06%)  4
Pulmonary sepsis  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Pulmonary tuberculosis  1  3/6932 (0.04%)  3 4/6910 (0.06%)  4
Pyelonephritis  1  4/6932 (0.06%)  5 5/6910 (0.07%)  5
Pyelonephritis acute  1  3/6932 (0.04%)  3 4/6910 (0.06%)  4
Pyelonephritis chronic  1  1/6932 (0.01%)  1 1/6910 (0.01%)  1
Rectal abscess  1  0/6932 (0.00%)  0 2/6910 (0.03%)  2
Respiratory tract infection  1  5/6932 (0.07%)  5 1/6910 (0.01%)  1
Rotavirus infection  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Salmonellosis  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Scrotal abscess  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Sepsis  1  21/6932 (0.30%)  22 21/6910 (0.30%)  21
Septic shock  1  13/6932 (0.19%)  14 11/6910 (0.16%)  11
Sialoadenitis  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Soft tissue infection  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Splenic abscess  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Staphylococcal infection  1  3/6932 (0.04%)  3 3/6910 (0.04%)  3
Staphylococcal sepsis  1  2/6932 (0.03%)  2 0/6910 (0.00%)  0
Streptococcal bacteraemia  1  0/6932 (0.00%)  0 2/6910 (0.03%)  2
Subcutaneous abscess  1  2/6932 (0.03%)  2 0/6910 (0.00%)  0
Subdiaphragmatic abscess  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Tetanus  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Tracheostomy infection  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Tuberculosis  1  0/6932 (0.00%)  0 3/6910 (0.04%)  3
Tuberculous pleurisy  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Upper respiratory tract infection  1  4/6932 (0.06%)  4 2/6910 (0.03%)  3
Urethral stricture post infection  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Urinary tract infection  1  40/6932 (0.58%)  48 32/6910 (0.46%)  34
Urinary tract infection bacterial  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Urinary tract infection fungal  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Urosepsis  1  4/6932 (0.06%)  4 13/6910 (0.19%)  15
Varicella zoster virus infection  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Vestibular neuronitis  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Viral infection  1  2/6932 (0.03%)  2 2/6910 (0.03%)  2
Wound infection  1  2/6932 (0.03%)  2 3/6910 (0.04%)  4
Wound infection bacterial  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Injury, poisoning and procedural complications     
Abdominal wound dehiscence  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Acetabulum fracture  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Alcohol poisoning  1  2/6932 (0.03%)  2 3/6910 (0.04%)  4
Anaemia postoperative  1  0/6932 (0.00%)  0 2/6910 (0.03%)  2
Anastomotic haemorrhage  1  1/6932 (0.01%)  1 1/6910 (0.01%)  1
Anastomotic ulcer haemorrhage  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Ankle fracture  1  4/6932 (0.06%)  4 5/6910 (0.07%)  5
Arthropod sting  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Avulsion fracture  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Burns second degree  1  1/6932 (0.01%)  1 2/6910 (0.03%)  2
Carotid artery restenosis  1  2/6932 (0.03%)  2 1/6910 (0.01%)  1
Cervical vertebral fracture  1  1/6932 (0.01%)  1 2/6910 (0.03%)  2
Chest injury  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Comminuted fracture  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Concussion  1  1/6932 (0.01%)  1 1/6910 (0.01%)  1
Contusion  1  1/6932 (0.01%)  1 2/6910 (0.03%)  2
Craniocerebral injury  1  2/6932 (0.03%)  2 1/6910 (0.01%)  1
Fall  1  8/6932 (0.12%)  8 8/6910 (0.12%)  10
Femoral neck fracture  1  11/6932 (0.16%)  11 12/6910 (0.17%)  12
Femur fracture  1  13/6932 (0.19%)  13 11/6910 (0.16%)  11
Fibula fracture  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Foot fracture  1  1/6932 (0.01%)  1 3/6910 (0.04%)  3
Forearm fracture  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Foreign body in eye  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Fracture  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Graft haemorrhage  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Gun shot wound  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Head injury  1  0/6932 (0.00%)  0 2/6910 (0.03%)  2
Heat exhaustion  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Heat illness  1  2/6932 (0.03%)  2 0/6910 (0.00%)  0
Hip fracture  1  13/6932 (0.19%)  13 12/6910 (0.17%)  12
Humerus fracture  1  10/6932 (0.14%)  10 5/6910 (0.07%)  5
Hypobarism  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Incision site erythema  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Incisional hernia  1  6/6932 (0.09%)  6 1/6910 (0.01%)  1
Intentional overdose  1  0/6932 (0.00%)  0 2/6910 (0.03%)  2
Joint dislocation  1  2/6932 (0.03%)  2 2/6910 (0.03%)  2
Laceration  1  2/6932 (0.03%)  2 1/6910 (0.01%)  1
Ligament rupture  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Ligament sprain  1  2/6932 (0.03%)  2 1/6910 (0.01%)  1
Limb injury  1  0/6932 (0.00%)  0 2/6910 (0.03%)  2
Lower limb fracture  1  3/6932 (0.04%)  3 2/6910 (0.03%)  2
Lumbar vertebral fracture  1  6/6932 (0.09%)  6 2/6910 (0.03%)  2
Lumbosacral plexus injury  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Meniscus injury  1  3/6932 (0.04%)  3 4/6910 (0.06%)  4
Multiple fractures  1  3/6932 (0.04%)  3 1/6910 (0.01%)  1
Multiple injuries  1  0/6932 (0.00%)  0 2/6910 (0.03%)  2
Muscle rupture  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Nerve injury  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Open globe injury  1  0/6932 (0.00%)  0 1/6910 (0.01%)  1
Pelvic fracture  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Periprosthetic fracture  1  2/6932 (0.03%)  2 0/6910 (0.00%)  0
Pneumothorax traumatic  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Post concussion syndrome  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Post procedural complication  1  1/6932 (0.01%)  1 0/6910 (0.00%)  0
Post procedural haematoma  1  0/6932 (0.00%)  0 3/6910 (0.04%)  3
Post procedural haematuria  1  0/6932 (0.00%)  0