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A Study Comparing Cardiovascular Effects of Ticagrelor Versus Placebo in Patients With Type 2 Diabetes Mellitus (THEMIS)

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: NCT01991795
Recruitment Status : Completed
First Posted : November 25, 2013
Results First Posted : March 18, 2020
Last Update Posted : March 18, 2020
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 Diabetes Mellitus, Type 2
Interventions Drug: Ticagrelor 60 mg
Drug: Ticagrelor placebo
Enrollment 19271
Recruitment Details 1315 study sites in 42 countries enrolled patients. The first patient was enrolled on 10 February 2014. The last patient visit took place on 25 January 2019.
Pre-assignment Details Enrolled patients randomised to study drug 95.8%; n =19271, of which 51 patients were randomised to study drug at a site prematurely closed by sponsor and excluded from the study results. Patients who were not randomised 4.2%; n=837. Patient did not meet inclusion/exclusion criteria n=454, Patient decision n=256, Death n=1, Other reason n=131.
Arm/Group Title Ticagrelor 60 mg Ticagrelor Placebo
Hide Arm/Group Description Initially ticagrelor 90 mg or corresponding placebo was the selected dose, but reduced to ticagrelor 60 mg or corresponding placebo in Clinical Study Protocol Amendment No 1. Initially ticagrelor 90 mg or corresponding placebo was the selected dose, but reduced to ticagrelor 60 mg or corresponding placebo in Clinical Study Protocol Amendment No 1.
Period Title: Overall Study
Started [1] 9645 9626
Completed [2] 9496 9503
Not Completed 149 123
Reason Not Completed
Lost to Follow-up             6             4
Withdrawal by Subject             117             94
Site prematurely closed by sponsor             26             25
[1]
Includes patients that were randomised to study drug
[2]
Patients who did not withdrew informed consent, were not LTFU and not excluded from the analyses
Arm/Group Title Ticagrelor 60 mg Ticagrelor Placebo Total
Hide Arm/Group Description Initially ticagrelor 90 mg or corresponding placebo was the selected dose, but reduced to ticagrelor 60 mg or corresponding placebo in Clinical Study Protocol Amendment No 1. Initially ticagrelor 90 mg or corresponding placebo was the selected dose, but reduced to ticagrelor 60 mg or corresponding placebo in Clinical Study Protocol Amendment No 1. Total of all reporting groups
Overall Number of Baseline Participants 9619 9601 19220
Hide Baseline Analysis Population Description
Of the 19271 patients randomised to study drug, 51 patients were randomised to study drug at a site prematurely closed by sponsor and excluded from the study results. 19220 were included in the evaluation of study results.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 9619 participants 9601 participants 19220 participants
66.3  (7.8) 66.3  (7.7) 66.3  (7.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9619 participants 9601 participants 19220 participants
Female
3043
  31.6%
2988
  31.1%
6031
  31.4%
Male
6576
  68.4%
6613
  68.9%
13189
  68.6%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
 Number Analyzed 9619 participants 9601 participants 19220 participants
White
6838
  71.1%
6858
  71.4%
13696
  71.3%
Black or african american
205
   2.1%
198
   2.1%
403
   2.1%
Asian
2211
  23.0%
2195
  22.9%
4406
  22.9%
Native hawaiian or other pacific islander
7
   0.1%
7
   0.1%
14
   0.1%
American indian or alaska native
161
   1.7%
152
   1.6%
313
   1.6%
Other
197
   2.0%
191
   2.0%
388
   2.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 9619 participants 9601 participants 19220 participants
USA 1126 1140 2266
Argentina 195 199 394
Australia 94 94 188
Austria 42 45 87
Belgium 109 108 217
Bulgaria 435 443 878
Brazil 412 399 811
Canada 364 365 729
Chile 152 148 300
China 456 454 910
Colombia 68 68 136
Czech Republic 304 298 602
Germany 277 270 547
Denmark 123 120 243
Spain 170 170 340
Finland 60 58 118
France 85 87 172
United Kingdom 123 123 246
Hong Kong 76 76 152
Hungary 306 310 616
India 147 145 292
Israel 60 57 117
Italy 67 63 130
Japan 246 250 496
Korea, Republic Of 433 437 870
Mexico 182 182 364
Netherlands 242 237 479
Norway 95 96 191
Peru 91 82 173
Philippines 47 45 92
Poland 815 821 1636
Romania 37 43 80
Russia 561 560 1121
Saudi Arabia 79 76 155
Slovakia 122 122 244
Sweden 110 114 224
Thailand 115 116 231
Turkey 113 112 225
Taiwan, Province Of China 402 401 803
Ukraine 399 393 792
Viet Nam 129 125 254
South Africa 150 149 299
1.Primary Outcome
Title Composite of Cardiovascular (CV) Death, MI or Stroke
Hide Description Participants with Cardiovascular (CV) death, myocardial infarction (MI) or stroke. If no event, censoring occurs at the earliest of PACD, last endpoint assessment date and non-CV death date.
Time Frame From randomisation to primary analysis censoring date (PACD). Median time in study until PACD was 40 months.
Hide Outcome Measure Data
Hide Analysis Population Description
The population was the full analysis set, which included all randomised patients except the 51 patients who were randomised to study drug at a site prematurely closed by sponsor.
Arm/Group Title Ticagrelor 60 mg Ticagrelor Placebo
Hide Arm/Group Description:
Initially ticagrelor 90 mg or corresponding placebo was the selected dose, but reduced to ticagrelor 60 mg or corresponding placebo in Clinical Study Protocol Amendment No 1.
Initially ticagrelor 90 mg or corresponding placebo was the selected dose, but reduced to ticagrelor 60 mg or corresponding placebo in Clinical Study Protocol Amendment No 1.
Overall Number of Participants Analyzed 9619 9601
Measure Type: Number
Unit of Measure: Number of participants with event
736 818
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ticagrelor 60 mg, Ticagrelor Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0378
Comments The hypothesis will be tested at the 4.96% 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 0.90
Confidence Interval (2-Sided) 95%
0.81 to 0.99
Estimation Comments [Not Specified]
2.Secondary Outcome
Title CV Death
Hide Description Participants with Cardiovascular (CV) death. If no event, censoring occurs at the earliest of PACD, last endpoint assessment date and non-CV death date.
Time Frame From randomisation to primary analysis censoring date (PACD). Median time in study until PACD was 40 months.
Hide Outcome Measure Data
Hide Analysis Population Description
The population was the full analysis set, which included all randomised patients except the 51 patients who were randomised to study drug at a site prematurely closed by sponsor.
Arm/Group Title Ticagrelor 60 mg Ticagrelor Placebo
Hide Arm/Group Description:
Initially ticagrelor 90 mg or corresponding placebo was the selected dose, but reduced to ticagrelor 60 mg or corresponding placebo in Clinical Study Protocol Amendment No 1.
Initially ticagrelor 90 mg or corresponding placebo was the selected dose, but reduced to ticagrelor 60 mg or corresponding placebo in Clinical Study Protocol Amendment No 1.
Overall Number of Participants Analyzed 9619 9601
Measure Type: Number
Unit of Measure: Number of participants with event
364 357
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ticagrelor 60 mg, Ticagrelor Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7883
Comments The hypothesis will be tested at the 4.96% 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%
0.88 to 1.18
Estimation Comments [Not Specified]
3.Secondary Outcome
Title MI
Hide Description Participants with myocardial infarction. If no event, censoring occurs at the earliest of primary analysis censoring date (PACD), last endpoint assessment date and death date
Time Frame From randomisation to primary analysis censoring date (PACD). Median time in study until PACD was 40 months.
Hide Outcome Measure Data
Hide Analysis Population Description
The population was the full analysis set, which included all randomised patients except the 51 patients who were randomised to study drug at a site prematurely closed by sponsor.
Arm/Group Title Ticagrelor 60 mg Ticagrelor Placebo
Hide Arm/Group Description:
Initially ticagrelor 90 mg or corresponding placebo was the selected dose, but reduced to ticagrelor 60 mg or corresponding placebo in Clinical Study Protocol Amendment No 1.
Initially ticagrelor 90 mg or corresponding placebo was the selected dose, but reduced to ticagrelor 60 mg or corresponding placebo in Clinical Study Protocol Amendment No 1.
Overall Number of Participants Analyzed 9619 9601
Measure Type: Number
Unit of Measure: Number of participants with event
274 328
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ticagrelor 60 mg, Ticagrelor Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0294
Comments The hypothesis will be tested at the 4.96% 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 0.84
Confidence Interval (2-Sided) 95%
0.71 to 0.98
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Ischaemic Stroke
Hide Description Participants with ischaemic stroke. If no event, censoring occurs at the earliest of PACD, last endpoint assessment date and death date.
Time Frame From randomisation to primary analysis censoring date (PACD). Median time in study until PACD was 40 months.
Hide Outcome Measure Data
Hide Analysis Population Description
The population was the full analysis set, which included all randomised patients except the 51 patients who were randomised to study drug at a site prematurely closed by sponsor.
Arm/Group Title Ticagrelor 60 mg Ticagrelor Placebo
Hide Arm/Group Description:
Initially ticagrelor 90 mg or corresponding placebo was the selected dose, but reduced to ticagrelor 60 mg or corresponding placebo in Clinical Study Protocol Amendment No 1.
Initially ticagrelor 90 mg or corresponding placebo was the selected dose, but reduced to ticagrelor 60 mg or corresponding placebo in Clinical Study Protocol Amendment No 1.
Overall Number of Participants Analyzed 9619 9601
Measure Type: Number
Unit of Measure: Number of participants with event
152 191
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ticagrelor 60 mg, Ticagrelor Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0375
Comments The hypothesis will be tested at the 4.96% 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 0.80
Confidence Interval (2-Sided) 95%
0.64 to 0.99
Estimation Comments [Not Specified]
5.Secondary Outcome
Title All-cause Death
Hide Description Participants with all-cause death. If no event, censoring occurs at the earliest of PACD and last endpoint assessment date. Includes deaths based on publically available vital status data in patients who have withdrawn consent.
Time Frame From randomisation to primary analysis censoring date (PACD). Median time in study until PACD was 40 months.
Hide Outcome Measure Data
Hide Analysis Population Description
The population was the full analysis set, which included all randomised patients except the 51 patients who were randomised to study drug at a site prematurely closed by sponsor.
Arm/Group Title Ticagrelor 60 mg Ticagrelor Placebo
Hide Arm/Group Description:
Initially ticagrelor 90 mg or corresponding placebo was the selected dose, but reduced to ticagrelor 60 mg or corresponding placebo in Clinical Study Protocol Amendment No 1.
Initially ticagrelor 90 mg or corresponding placebo was the selected dose, but reduced to ticagrelor 60 mg or corresponding placebo in Clinical Study Protocol Amendment No 1.
Overall Number of Participants Analyzed 9619 9601
Measure Type: Number
Unit of Measure: Number of participants with event
579 592
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ticagrelor 60 mg, Ticagrelor Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6846
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.98
Confidence Interval (2-Sided) 95%
0.87 to 1.10
Estimation Comments [Not Specified]
6.Other Pre-specified Outcome
Title TIMI Major Bleeding Event (Primary Safety Objective)
Hide Description Participants with TIMI major bleeding event. If no event, censoring occurs at the earliest of last endpoint assessment date, death date and 7 days following the date of last dose of study medication
Time Frame From randomisation to 7 days following the date of last dose of study medication. Maximum duration of exposure was 59 months.
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 randomised ticagrelor or placebo
Arm/Group Title Ticagrelor 60 mg Ticagrelor Placebo
Hide Arm/Group Description:
Initially ticagrelor 90 mg or corresponding placebo was the selected dose, but reduced to ticagrelor 60 mg or corresponding placebo in Clinical Study Protocol Amendment No 1.
Initially ticagrelor 90 mg or corresponding placebo was the selected dose, but reduced to ticagrelor 60 mg or corresponding placebo in Clinical Study Protocol Amendment No 1.
Overall Number of Participants Analyzed 9562 9531
Measure Type: Number
Unit of Measure: Number of participants with event
206 100
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ticagrelor 60 mg, Ticagrelor Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 2.32
Confidence Interval (2-Sided) 95%
1.82 to 2.94
Estimation Comments [Not Specified]
7.Other Pre-specified Outcome
Title TIMI Major or Minor Bleeding Event
Hide Description Participants with TIMI major or minor bleeding event. If no event, censoring occurs at the earliest of last endpoint assessment date, death date and 7 days following the date of last dose of study medication
Time Frame From randomisation to 7 days following the date of last dose of study medication. Maximum duration of exposure was 59 months.
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 randomised ticagrelor or placebo
Arm/Group Title Ticagrelor 60 mg Ticagrelor Placebo
Hide Arm/Group Description:
Initially ticagrelor 90 mg or corresponding placebo was the selected dose, but reduced to ticagrelor 60 mg or corresponding placebo in Clinical Study Protocol Amendment No 1.
Initially ticagrelor 90 mg or corresponding placebo was the selected dose, but reduced to ticagrelor 60 mg or corresponding placebo in Clinical Study Protocol Amendment No 1.
Overall Number of Participants Analyzed 9562 9531
Measure Type: Number
Unit of Measure: Number of participants with event
285 129
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ticagrelor 60 mg, Ticagrelor Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 2.49
Confidence Interval (2-Sided) 95%
2.02 to 3.07
Estimation Comments [Not Specified]
8.Other Pre-specified Outcome
Title PLATO Major Bleeding Event
Hide Description Participants with PLATO major bleeding event. If no event, censoring occurs at the earliest of last endpoint assessment date, death date and 7 days following the date of last dose of study medication
Time Frame From randomisation to 7 days following the date of last dose of study medication. Maximum duration of exposure was 59 months.
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 randomised ticagrelor or placebo
Arm/Group Title Ticagrelor 60 mg Ticagrelor Placebo
Hide Arm/Group Description:
Initially ticagrelor 90 mg or corresponding placebo was the selected dose, but reduced to ticagrelor 60 mg or corresponding placebo in Clinical Study Protocol Amendment No 1.
Initially ticagrelor 90 mg or corresponding placebo was the selected dose, but reduced to ticagrelor 60 mg or corresponding placebo in Clinical Study Protocol Amendment No 1.
Overall Number of Participants Analyzed 9562 9531
Measure Type: Number
Unit of Measure: Number of participants with event
310 145
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ticagrelor 60 mg, Ticagrelor Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 2.41
Confidence Interval (2-Sided) 95%
1.98 to 2.93
Estimation Comments [Not Specified]
9.Other Pre-specified Outcome
Title Permanent Discontinuation of Study Medication Due to Any Bleeding Event
Hide Description Participants with permanent discontinuation of study medication due to any bleeding event. If no event, censoring occurs at the earliest of last endpoint assessment date, death date and the date of last dose of study medication
Time Frame From randomisation to 7 days following the date of last dose of study medication. Maximum duration of exposure was 59 months.
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 randomised ticagrelor or placebo
Arm/Group Title Ticagrelor 60 mg Ticagrelor Placebo
Hide Arm/Group Description:
Initially ticagrelor 90 mg or corresponding placebo was the selected dose, but reduced to ticagrelor 60 mg or corresponding placebo in Clinical Study Protocol Amendment No 1.
Initially ticagrelor 90 mg or corresponding placebo was the selected dose, but reduced to ticagrelor 60 mg or corresponding placebo in Clinical Study Protocol Amendment No 1.
Overall Number of Participants Analyzed 9562 9531
Measure Type: Number
Unit of Measure: Number of participants with event
466 125
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ticagrelor 60 mg, Ticagrelor Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 4.04
Confidence Interval (2-Sided) 95%
3.32 to 4.92
Estimation Comments [Not Specified]
Time Frame All-cause death includes all deaths that occur between randomisation and last visit (before and after primary analysis censoring date, and including vital status known from public records). The other adverse event categories are presented with event onset date between randomisation to 7 days following the date of last dose of study medication. Maximum duration of exposure was 59 months.
Adverse Event Reporting Description

All-cause death was assessed for all randomised participants, except the 51 patients who were randomised to study drug at a site prematurely closed by sponsor.

Systematic assessment of suspected bleeding events, suspected endpoint events, SAEs, AEs that leads to permanent discontinuation of study drug and non-serious AEs of interest. The analysis set included all patients who received at least 1 dose of study drug, except those patients randomised at the prematurely closed site.
 
Arm/Group Title Ticagrelor 60 mg Ticagrelor Placebo
Hide Arm/Group Description Initially ticagrelor 90 mg or corresponding placebo was the selected dose, but reduced to ticagrelor 60 mg or corresponding placebo in Clinical Study Protocol Amendment No 1. Initially ticagrelor 90 mg or corresponding placebo was the selected dose, but reduced to ticagrelor 60 mg or corresponding placebo in Clinical Study Protocol Amendment No 1.
All-Cause Mortality
Ticagrelor 60 mg Ticagrelor Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   589/9619 (6.12%)      602/9601 (6.27%)    
Hide Serious Adverse Events
Ticagrelor 60 mg Ticagrelor Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3049/9562 (31.89%)      3210/9531 (33.68%)    
Blood and lymphatic system disorders     
Abdominal lymphadenopathy † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Agranulocytosis † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Anaemia † 1  20/9562 (0.21%)  20 14/9531 (0.15%)  14
Anaemia macrocytic † 1  3/9562 (0.03%)  3 0/9531 (0.00%)  0
Anaemia of chronic disease † 1  2/9562 (0.02%)  2 1/9531 (0.01%)  1
Anaemia of malignant disease † 1  2/9562 (0.02%)  2 1/9531 (0.01%)  1
Anaemia vitamin b12 deficiency † 1  1/9562 (0.01%)  1 1/9531 (0.01%)  1
Deficiency anaemia † 1  2/9562 (0.02%)  2 1/9531 (0.01%)  1
Disseminated intravascular coagulation † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Haemorrhagic anaemia † 1  10/9562 (0.10%)  10 3/9531 (0.03%)  3
Hypochromic anaemia † 1  1/9562 (0.01%)  1 1/9531 (0.01%)  1
Immune thrombocytopenic purpura † 1  1/9562 (0.01%)  1 1/9531 (0.01%)  1
Increased tendency to bruise † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Iron deficiency anaemia † 1  26/9562 (0.27%)  26 6/9531 (0.06%)  6
Leukocytosis † 1  2/9562 (0.02%)  2 1/9531 (0.01%)  1
Lymphadenopathy † 1  1/9562 (0.01%)  1 1/9531 (0.01%)  1
Microcytic anaemia † 1  3/9562 (0.03%)  3 1/9531 (0.01%)  1
Nephrogenic anaemia † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Neutropenia † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Normochromic normocytic anaemia † 1  2/9562 (0.02%)  2 0/9531 (0.00%)  0
Normocytic anaemia † 1  2/9562 (0.02%)  3 1/9531 (0.01%)  1
Pancytopenia † 1  3/9562 (0.03%)  3 0/9531 (0.00%)  0
Splenic infarction † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Spontaneous haematoma † 1  3/9562 (0.03%)  3 2/9531 (0.02%)  2
Spontaneous haemorrhage † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Thrombocytopenia † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Cardiac disorders     
Acute coronary syndrome † 1  20/9562 (0.21%)  20 22/9531 (0.23%)  22
Acute left ventricular failure † 1  5/9562 (0.05%)  6 2/9531 (0.02%)  2
Acute myocardial infarction † 1  126/9562 (1.32%)  133 197/9531 (2.07%)  203
Adams-stokes syndrome † 1  2/9562 (0.02%)  2 0/9531 (0.00%)  0
Angina pectoris † 1  200/9562 (2.09%)  239 251/9531 (2.63%)  267
Angina unstable † 1  354/9562 (3.70%)  403 405/9531 (4.25%)  449
Aortic valve disease † 1  1/9562 (0.01%)  1 1/9531 (0.01%)  1
Aortic valve incompetence † 1  1/9562 (0.01%)  1 2/9531 (0.02%)  2
Aortic valve stenosis † 1  8/9562 (0.08%)  8 14/9531 (0.15%)  14
Arrhythmia † 1  0/9562 (0.00%)  0 3/9531 (0.03%)  5
Arteriosclerosis coronary artery † 1  9/9562 (0.09%)  9 8/9531 (0.08%)  8
Atrial fibrillation † 1  82/9562 (0.86%)  84 76/9531 (0.80%)  80
Atrial flutter † 1  12/9562 (0.13%)  13 13/9531 (0.14%)  14
Atrial tachycardia † 1  2/9562 (0.02%)  2 4/9531 (0.04%)  4
Atrial thrombosis † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Atrioventricular block † 1  2/9562 (0.02%)  2 2/9531 (0.02%)  2
Atrioventricular block complete † 1  16/9562 (0.17%)  16 18/9531 (0.19%)  18
Atrioventricular block first degree † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Atrioventricular block second degree † 1  12/9562 (0.13%)  12 6/9531 (0.06%)  6
Bifascicular block † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Bradyarrhythmia † 1  2/9562 (0.02%)  2 2/9531 (0.02%)  2
Bradycardia † 1  15/9562 (0.16%)  15 6/9531 (0.06%)  6
Bundle branch block left † 1  1/9562 (0.01%)  1 1/9531 (0.01%)  1
Bundle branch block right † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Cardiac arrest † 1  7/9562 (0.07%)  7 12/9531 (0.13%)  12
Cardiac disorder † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Cardiac failure † 1  64/9562 (0.67%)  84 87/9531 (0.91%)  108
Cardiac failure acute † 1  20/9562 (0.21%)  27 14/9531 (0.15%)  15
Cardiac failure chronic † 1  18/9562 (0.19%)  19 30/9531 (0.31%)  44
Cardiac failure congestive † 1  60/9562 (0.63%)  71 47/9531 (0.49%)  53
Cardiac tamponade † 1  0/9562 (0.00%)  0 2/9531 (0.02%)  2
Cardiac valve disease † 1  0/9562 (0.00%)  0 2/9531 (0.02%)  2
Cardiac ventricular scarring † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Cardio-respiratory arrest † 1  3/9562 (0.03%)  3 3/9531 (0.03%)  3
Cardiogenic shock † 1  6/9562 (0.06%)  6 4/9531 (0.04%)  4
Cardiomyopathy † 1  1/9562 (0.01%)  1 2/9531 (0.02%)  2
Cardiopulmonary failure † 1  1/9562 (0.01%)  1 2/9531 (0.02%)  2
Cardiovascular insufficiency † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Coronary artery disease † 1  85/9562 (0.89%)  89 90/9531 (0.94%)  95
Coronary artery insufficiency † 1  2/9562 (0.02%)  2 2/9531 (0.02%)  2
Coronary artery occlusion † 1  2/9562 (0.02%)  2 2/9531 (0.02%)  2
Coronary artery stenosis † 1  14/9562 (0.15%)  14 4/9531 (0.04%)  4
Dressler's syndrome † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Extrasystoles † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Hypertensive heart disease † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Ischaemic cardiomyopathy † 1  3/9562 (0.03%)  3 2/9531 (0.02%)  4
Left ventricular dysfunction † 1  1/9562 (0.01%)  1 1/9531 (0.01%)  1
Left ventricular failure † 1  7/9562 (0.07%)  8 4/9531 (0.04%)  4
Microvascular coronary artery disease † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Mitral valve incompetence † 1  2/9562 (0.02%)  2 3/9531 (0.03%)  3
Mitral valve stenosis † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Myocardial fibrosis † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Myocardial infarction † 1  41/9562 (0.43%)  43 65/9531 (0.68%)  66
Myocardial ischaemia † 1  36/9562 (0.38%)  37 47/9531 (0.49%)  50
Myocarditis † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Nodal arrhythmia † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Palpitations † 1  4/9562 (0.04%)  4 2/9531 (0.02%)  2
Pericardial effusion † 1  2/9562 (0.02%)  2 1/9531 (0.01%)  1
Pericardial haemorrhage † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Pericarditis † 1  3/9562 (0.03%)  3 0/9531 (0.00%)  0
Pericarditis constrictive † 1  1/9562 (0.01%)  1 1/9531 (0.01%)  1
Prinzmetal angina † 1  0/9562 (0.00%)  0 3/9531 (0.03%)  4
Pulmonary valve incompetence † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Right ventricular failure † 1  1/9562 (0.01%)  1 2/9531 (0.02%)  2
Sinoatrial block † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Sinus arrhythmia † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Sinus bradycardia † 1  7/9562 (0.07%)  7 4/9531 (0.04%)  4
Sinus node dysfunction † 1  5/9562 (0.05%)  5 4/9531 (0.04%)  4
Sinus tachycardia † 1  1/9562 (0.01%)  1 1/9531 (0.01%)  1
Stress cardiomyopathy † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Supraventricular extrasystoles † 1  3/9562 (0.03%)  3 2/9531 (0.02%)  2
Supraventricular tachycardia † 1  5/9562 (0.05%)  5 9/9531 (0.09%)  11
Tachycardia † 1  1/9562 (0.01%)  2 4/9531 (0.04%)  4
Tricuspid valve incompetence † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Ventricular arrhythmia † 1  1/9562 (0.01%)  1 2/9531 (0.02%)  2
Ventricular asystole † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Ventricular extrasystoles † 1  4/9562 (0.04%)  4 7/9531 (0.07%)  7
Ventricular fibrillation † 1  2/9562 (0.02%)  2 3/9531 (0.03%)  3
Ventricular tachycardia † 1  10/9562 (0.10%)  10 6/9531 (0.06%)  6
Congenital, familial and genetic disorders     
Corneal dystrophy † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Glucose-6-phosphate dehydrogenase deficiency † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Neurofibromatosis † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Ear and labyrinth disorders     
Deafness † 1  1/9562 (0.01%)  1 2/9531 (0.02%)  2
Deafness neurosensory † 1  0/9562 (0.00%)  0 2/9531 (0.02%)  2
Deafness unilateral † 1  3/9562 (0.03%)  3 0/9531 (0.00%)  0
Ear pain † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Eustachian tube dysfunction † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Hypoacusis † 1  1/9562 (0.01%)  1 1/9531 (0.01%)  1
Inner ear disorder † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Meniere's disease † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Sudden hearing loss † 1  2/9562 (0.02%)  2 1/9531 (0.01%)  1
Tinnitus † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Tympanic membrane perforation † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Tympanosclerosis † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Vertigo † 1  13/9562 (0.14%)  13 7/9531 (0.07%)  7
Vertigo positional † 1  7/9562 (0.07%)  7 3/9531 (0.03%)  3
Vestibular disorder † 1  2/9562 (0.02%)  2 2/9531 (0.02%)  2
Endocrine disorders     
Adrenal insufficiency † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Goitre † 1  5/9562 (0.05%)  6 2/9531 (0.02%)  2
Hyperparathyroidism † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Hyperparathyroidism primary † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Hyperthyroidism † 1  1/9562 (0.01%)  1 2/9531 (0.02%)  2
Hypothyroidism † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Thyroiditis subacute † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Eye disorders     
Age-related macular degeneration † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Aphakia † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Cataract † 1  22/9562 (0.23%)  26 30/9531 (0.31%)  35
Cataract cortical † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Cataract diabetic † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Cataract nuclear † 1  1/9562 (0.01%)  1 1/9531 (0.01%)  1
Corneal degeneration † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Diabetic retinopathy † 1  3/9562 (0.03%)  5 4/9531 (0.04%)  4
Entropion † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Eye haemorrhage † 1  4/9562 (0.04%)  4 1/9531 (0.01%)  1
Eyelid ptosis † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Glaucoma † 1  2/9562 (0.02%)  2 3/9531 (0.03%)  4
Lacrimal disorder † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Macular degeneration † 1  1/9562 (0.01%)  1 1/9531 (0.01%)  1
Macular fibrosis † 1  2/9562 (0.02%)  2 2/9531 (0.02%)  2
Macular oedema † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Macular pseudohole † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Maculopathy † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Open angle glaucoma † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Optic ischaemic neuropathy † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Retinal artery occlusion † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Retinal artery thrombosis † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Retinal degeneration † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Retinal detachment † 1  2/9562 (0.02%)  2 3/9531 (0.03%)  3
Retinal haemorrhage † 1  2/9562 (0.02%)  2 5/9531 (0.05%)  5
Retinal vein occlusion † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Retinal vein thrombosis † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Retinopathy † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Retinopathy proliferative † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Rhegmatogenous retinal detachment † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Strabismus † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Trichiasis † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Ulcerative keratitis † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Visual impairment † 1  1/9562 (0.01%)  1 1/9531 (0.01%)  1
Vitreous haemorrhage † 1  9/9562 (0.09%)  9 5/9531 (0.05%)  5
Vitreous opacities † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Gastrointestinal disorders     
Abdominal discomfort † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Abdominal distension † 1  2/9562 (0.02%)  4 0/9531 (0.00%)  0
Abdominal hernia † 1  2/9562 (0.02%)  2 3/9531 (0.03%)  3
Abdominal pain † 1  7/9562 (0.07%)  7 4/9531 (0.04%)  4
Abdominal pain lower † 1  1/9562 (0.01%)  1 2/9531 (0.02%)  2
Abdominal pain upper † 1  1/9562 (0.01%)  1 5/9531 (0.05%)  5
Abdominal wall haematoma † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Anal fissure † 1  0/9562 (0.00%)  0 3/9531 (0.03%)  3
Anal fistula † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Anal haemorrhage † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Anal inflammation † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Appendicitis noninfective † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Appendix disorder † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Ascites † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Barrett's oesophagus † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Bezoar † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Change of bowel habit † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Chronic gastritis † 1  2/9562 (0.02%)  2 4/9531 (0.04%)  4
Chronic gastrointestinal bleeding † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Coeliac disease † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Colitis † 1  4/9562 (0.04%)  4 5/9531 (0.05%)  5
Colitis ischaemic † 1  1/9562 (0.01%)  1 1/9531 (0.01%)  1
Constipation † 1  4/9562 (0.04%)  4 3/9531 (0.03%)  3
Dental caries † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Diabetic gastroparesis † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  2
Diaphragmatic hernia † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Diarrhoea † 1  18/9562 (0.19%)  18 8/9531 (0.08%)  8
Diverticular perforation † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Diverticulitis oesophageal † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Diverticulum † 1  3/9562 (0.03%)  3 2/9531 (0.02%)  2
Diverticulum intestinal † 1  4/9562 (0.04%)  4 4/9531 (0.04%)  4
Diverticulum intestinal haemorrhagic † 1  5/9562 (0.05%)  6 2/9531 (0.02%)  2
Duodenal polyp † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Duodenal ulcer † 1  4/9562 (0.04%)  4 3/9531 (0.03%)  3
Duodenal ulcer haemorrhage † 1  7/9562 (0.07%)  8 4/9531 (0.04%)  4
Duodenitis † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Dyspepsia † 1  3/9562 (0.03%)  3 1/9531 (0.01%)  1
Dysphagia † 1  2/9562 (0.02%)  2 3/9531 (0.03%)  3
Enteritis † 1  2/9562 (0.02%)  2 4/9531 (0.04%)  4
Enterocolitis † 1  1/9562 (0.01%)  1 2/9531 (0.02%)  2
Epigastric discomfort † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Erosive oesophagitis † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Faecaloma † 1  1/9562 (0.01%)  1 1/9531 (0.01%)  1
Faeces discoloured † 1  2/9562 (0.02%)  2 0/9531 (0.00%)  0
Food poisoning † 1  0/9562 (0.00%)  0 2/9531 (0.02%)  2
Functional gastrointestinal disorder † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Gastric antral vascular ectasia † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Gastric disorder † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Gastric haemorrhage † 1  6/9562 (0.06%)  6 0/9531 (0.00%)  0
Gastric polyps † 1  5/9562 (0.05%)  5 6/9531 (0.06%)  8
Gastric ulcer † 1  18/9562 (0.19%)  18 9/9531 (0.09%)  9
Gastric ulcer haemorrhage † 1  6/9562 (0.06%)  6 3/9531 (0.03%)  3
Gastric ulcer perforation † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Gastritis † 1  8/9562 (0.08%)  8 12/9531 (0.13%)  12
Gastritis erosive † 1  9/9562 (0.09%)  9 2/9531 (0.02%)  2
Gastritis haemorrhagic † 1  6/9562 (0.06%)  6 1/9531 (0.01%)  1
Gastroduodenal ulcer † 1  2/9562 (0.02%)  2 0/9531 (0.00%)  0
Gastrointestinal angiodysplasia † 1  2/9562 (0.02%)  2 1/9531 (0.01%)  1
Gastrointestinal disorder † 1  2/9562 (0.02%)  2 1/9531 (0.01%)  1
Gastrointestinal haemorrhage † 1  43/9562 (0.45%)  44 22/9531 (0.23%)  23
Gastrointestinal inflammation † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Gastrointestinal ischaemia † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Gastrointestinal motility disorder † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Gastrointestinal polyp haemorrhage † 1  2/9562 (0.02%)  2 1/9531 (0.01%)  1
Gastrointestinal stenosis † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Gastrointestinal ulcer haemorrhage † 1  3/9562 (0.03%)  3 2/9531 (0.02%)  2
Gastrooesophageal reflux disease † 1  5/9562 (0.05%)  6 7/9531 (0.07%)  7
Haematemesis † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Haematochezia † 1  4/9562 (0.04%)  4 2/9531 (0.02%)  2
Haemorrhagic erosive gastritis † 1  1/9562 (0.01%)  1 2/9531 (0.02%)  2
Haemorrhoidal haemorrhage † 1  3/9562 (0.03%)  3 0/9531 (0.00%)  0
Haemorrhoids † 1  5/9562 (0.05%)  5 2/9531 (0.02%)  2
Hernial eventration † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Hiatus hernia † 1  1/9562 (0.01%)  1 2/9531 (0.02%)  2
Ileus † 1  4/9562 (0.04%)  5 3/9531 (0.03%)  3
Ileus paralytic † 1  2/9562 (0.02%)  2 0/9531 (0.00%)  0
Incarcerated inguinal hernia † 1  1/9562 (0.01%)  1 2/9531 (0.02%)  2
Inguinal hernia † 1  16/9562 (0.17%)  16 20/9531 (0.21%)  20
Intestinal haemorrhage † 1  6/9562 (0.06%)  6 3/9531 (0.03%)  3
Intestinal ischaemia † 1  0/9562 (0.00%)  0 3/9531 (0.03%)  3
Intestinal obstruction † 1  4/9562 (0.04%)  6 5/9531 (0.05%)  5
Intestinal perforation † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Intestinal polyp † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Intestinal pseudo-obstruction † 1  1/9562 (0.01%)  2 0/9531 (0.00%)  0
Intestinal strangulation † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Large intestinal haemorrhage † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Large intestine perforation † 1  1/9562 (0.01%)  1 2/9531 (0.02%)  2
Large intestine polyp † 1  18/9562 (0.19%)  18 14/9531 (0.15%)  14
Lower gastrointestinal haemorrhage † 1  3/9562 (0.03%)  3 3/9531 (0.03%)  3
Lumbar hernia † 1  0/9562 (0.00%)  0 2/9531 (0.02%)  2
Mallory-weiss syndrome † 1  2/9562 (0.02%)  2 1/9531 (0.01%)  1
Mechanical ileus † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Melaena † 1  12/9562 (0.13%)  12 4/9531 (0.04%)  4
Nausea † 1  0/9562 (0.00%)  0 2/9531 (0.02%)  2
Obstruction gastric † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Obstructive pancreatitis † 1  2/9562 (0.02%)  2 2/9531 (0.02%)  2
Oesophageal motility disorder † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Oesophageal spasm † 1  1/9562 (0.01%)  2 0/9531 (0.00%)  0
Oesophageal ulcer † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Oesophageal ulcer haemorrhage † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Oesophagitis † 1  2/9562 (0.02%)  2 1/9531 (0.01%)  1
Oesophagitis ulcerative † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Pancreatic mass † 1  1/9562 (0.01%)  1 1/9531 (0.01%)  1
Pancreatic pseudocyst † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Pancreatitis † 1  11/9562 (0.12%)  14 7/9531 (0.07%)  7
Pancreatitis acute † 1  2/9562 (0.02%)  2 5/9531 (0.05%)  6
Pancreatitis chronic † 1  4/9562 (0.04%)  4 2/9531 (0.02%)  2
Pancreatolithiasis † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Peptic ulcer † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Peptic ulcer haemorrhage † 1  2/9562 (0.02%)  2 0/9531 (0.00%)  0
Periodontal disease † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Peritoneal adhesions † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Peritoneal haemorrhage † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Proctitis † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Rectal haemorrhage † 1  13/9562 (0.14%)  13 2/9531 (0.02%)  2
Rectal polyp † 1  1/9562 (0.01%)  1 1/9531 (0.01%)  1
Rectal prolapse † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Reflux gastritis † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Salivary gland calculus † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Small intestinal haemorrhage † 1  2/9562 (0.02%)  2 0/9531 (0.00%)  0
Small intestinal obstruction † 1  3/9562 (0.03%)  3 4/9531 (0.04%)  4
Subileus † 1  2/9562 (0.02%)  2 1/9531 (0.01%)  1
Swollen tongue † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  2
Tooth disorder † 1  1/9562 (0.01%)  1 1/9531 (0.01%)  1
Tooth socket haemorrhage † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Ulcerative gastritis † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Umbilical hernia † 1  4/9562 (0.04%)  4 2/9531 (0.02%)  2
Umbilical hernia, obstructive † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Upper gastrointestinal haemorrhage † 1  22/9562 (0.23%)  23 10/9531 (0.10%)  10
Varices oesophageal † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Vomiting † 1  2/9562 (0.02%)  2 2/9531 (0.02%)  2
General disorders     
Administration site phlebitis † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Asthenia † 1  4/9562 (0.04%)  4 1/9531 (0.01%)  1
Capsular contracture associated with breast implant † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Cardiac death † 1  4/9562 (0.04%)  4 1/9531 (0.01%)  1
Catheter site haemorrhage † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Chest discomfort † 1  5/9562 (0.05%)  5 0/9531 (0.00%)  0
Chest pain † 1  6/9562 (0.06%)  6 11/9531 (0.12%)  11
Complication associated with device † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Death † 1  52/9562 (0.54%)  52 60/9531 (0.63%)  60
Drowning † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Facial pain † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Fatigue † 1  1/9562 (0.01%)  1 1/9531 (0.01%)  1
Foreign body reaction † 1  2/9562 (0.02%)  2 0/9531 (0.00%)  0
Gait disturbance † 1  1/9562 (0.01%)  1 1/9531 (0.01%)  1
Gait inability † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
General physical health deterioration † 1  2/9562 (0.02%)  2 1/9531 (0.01%)  1
Impaired healing † 1  1/9562 (0.01%)  1 1/9531 (0.01%)  1
Medical device site haemorrhage † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Mucosal exfoliation † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Multiple organ dysfunction syndrome † 1  2/9562 (0.02%)  2 0/9531 (0.00%)  0
Necrobiosis † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Necrosis † 1  2/9562 (0.02%)  2 2/9531 (0.02%)  2
Nodule † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Non-cardiac chest pain † 1  54/9562 (0.56%)  60 66/9531 (0.69%)  72
Oedema † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Oedema peripheral † 1  1/9562 (0.01%)  1 4/9531 (0.04%)  4
Pacemaker generated arrhythmia † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Pain † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Peripheral swelling † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Pyrexia † 1  8/9562 (0.08%)  8 6/9531 (0.06%)  6
Sudden cardiac death † 1  6/9562 (0.06%)  6 8/9531 (0.08%)  8
Sudden death † 1  5/9562 (0.05%)  5 5/9531 (0.05%)  5
Ulcer haemorrhage † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Vascular stent occlusion † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Vascular stent stenosis † 1  6/9562 (0.06%)  6 4/9531 (0.04%)  5
Hepatobiliary disorders     
Acute hepatic failure † 1  3/9562 (0.03%)  3 0/9531 (0.00%)  0
Bile duct obstruction † 1  2/9562 (0.02%)  2 2/9531 (0.02%)  2
Bile duct stone † 1  7/9562 (0.07%)  7 3/9531 (0.03%)  3
Biliary colic † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  2
Biliary dyskinesia † 1  2/9562 (0.02%)  2 0/9531 (0.00%)  0
Cholangitis † 1  1/9562 (0.01%)  1 4/9531 (0.04%)  5
Cholangitis acute † 1  3/9562 (0.03%)  3 3/9531 (0.03%)  3
Cholangitis chronic † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Cholecystitis † 1  13/9562 (0.14%)  14 23/9531 (0.24%)  27
Cholecystitis acute † 1  19/9562 (0.20%)  19 14/9531 (0.15%)  15
Cholecystitis chronic † 1  5/9562 (0.05%)  5 6/9531 (0.06%)  6
Cholelithiasis † 1  23/9562 (0.24%)  24 25/9531 (0.26%)  25
Cholestasis † 1  0/9562 (0.00%)  0 2/9531 (0.02%)  2
Chronic hepatitis † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Cirrhosis alcoholic † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Drug-induced liver injury † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Gallbladder disorder † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Hepatic cirrhosis † 1  4/9562 (0.04%)  4 7/9531 (0.07%)  7
Hepatic failure † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Hepatic function abnormal † 1  1/9562 (0.01%)  1 2/9531 (0.02%)  2
Hepatitis † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Hepatitis acute † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Jaundice † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Jaundice cholestatic † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Liver injury † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Non-alcoholic steatohepatitis † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Portal vein thrombosis † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Steatohepatitis † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Immune system disorders     
Allergy to arthropod bite † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Anaphylactic reaction † 1  0/9562 (0.00%)  0 4/9531 (0.04%)  4
Anaphylactic shock † 1  2/9562 (0.02%)  2 1/9531 (0.01%)  1
Contrast media allergy † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Drug hypersensitivity † 1  0/9562 (0.00%)  0 4/9531 (0.04%)  4
Haemophagocytic lymphohistiocytosis † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Sarcoidosis † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Transplant rejection † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Infections and infestations     
Abdominal abscess † 1  1/9562 (0.01%)  1 2/9531 (0.02%)  2
Abdominal sepsis † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Abdominal wall abscess † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Abscess jaw † 1  1/9562 (0.01%)  1 1/9531 (0.01%)  1
Abscess limb † 1  5/9562 (0.05%)  5 1/9531 (0.01%)  1
Abscess neck † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Acinetobacter infection † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Acute endocarditis † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Acute hepatitis b † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Acute sinusitis † 1  1/9562 (0.01%)  1 1/9531 (0.01%)  1
Anal abscess † 1  3/9562 (0.03%)  3 2/9531 (0.02%)  2
Anal fistula infection † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Appendiceal abscess † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Appendicitis † 1  13/9562 (0.14%)  14 10/9531 (0.10%)  10
Appendicitis perforated † 1  3/9562 (0.03%)  3 0/9531 (0.00%)  0
Arthritis infective † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Atypical pneumonia † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Bacteraemia † 1  2/9562 (0.02%)  2 1/9531 (0.01%)  1
Bacterial diarrhoea † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Bacterial sepsis † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Biliary sepsis † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Brain abscess † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Breast abscess † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Breast cellulitis † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Bronchiolitis † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Bronchitis † 1  18/9562 (0.19%)  18 22/9531 (0.23%)  23
Bronchitis bacterial † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Bursitis infective † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Campylobacter gastroenteritis † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Cellulitis † 1  35/9562 (0.37%)  40 45/9531 (0.47%)  51
Cellulitis gangrenous † 1  0/9562 (0.00%)  0 2/9531 (0.02%)  2
Cellulitis of male external genital organ † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Cholangitis infective † 1  2/9562 (0.02%)  2 1/9531 (0.01%)  1
Cholecystitis infective † 1  3/9562 (0.03%)  3 2/9531 (0.02%)  2
Chronic hepatitis c † 1  1/9562 (0.01%)  1 2/9531 (0.02%)  2
Chronic sinusitis † 1  1/9562 (0.01%)  1 2/9531 (0.02%)  2
Clostridium difficile colitis † 1  1/9562 (0.01%)  1 1/9531 (0.01%)  1
Clostridium difficile infection † 1  2/9562 (0.02%)  2 3/9531 (0.03%)  5
Complicated appendicitis † 1  1/9562 (0.01%)  1 1/9531 (0.01%)  1
Cystitis † 1  4/9562 (0.04%)  4 4/9531 (0.04%)  4
Dacryocystitis † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Dengue fever † 1  1/9562 (0.01%)  1 1/9531 (0.01%)  1
Dengue haemorrhagic fever † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Device related infection † 1  1/9562 (0.01%)  1 1/9531 (0.01%)  1
Device related sepsis † 1  2/9562 (0.02%)  2 0/9531 (0.00%)  0
Diabetic foot infection † 1  3/9562 (0.03%)  4 3/9531 (0.03%)  4
Diabetic gangrene † 1  1/9562 (0.01%)  1 1/9531 (0.01%)  1
Diarrhoea infectious † 1  2/9562 (0.02%)  2 0/9531 (0.00%)  0
Diverticulitis † 1  11/9562 (0.12%)  12 4/9531 (0.04%)  4
Diverticulitis intestinal haemorrhagic † 1  3/9562 (0.03%)  3 2/9531 (0.02%)  2
Dysentery † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Ear infection † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Emphysematous cystitis † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Endocarditis † 1  0/9562 (0.00%)  0 5/9531 (0.05%)  5
Endophthalmitis † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  2
Enteritis infectious † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Enterobacter pneumonia † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Enterocolitis infectious † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Epididymitis † 1  4/9562 (0.04%)  4 0/9531 (0.00%)  0
Epiglottitis † 1  1/9562 (0.01%)  1 2/9531 (0.02%)  3
Erysipelas † 1  12/9562 (0.13%)  12 10/9531 (0.10%)  13
Escherichia urinary tract infection † 1  2/9562 (0.02%)  2 2/9531 (0.02%)  2
Eye infection viral † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Febrile infection † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Fungal infection † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Gangrene † 1  5/9562 (0.05%)  5 12/9531 (0.13%)  13
Gastroenteritis † 1  14/9562 (0.15%)  15 18/9531 (0.19%)  19
Gastroenteritis bacterial † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Gastroenteritis salmonella † 1  0/9562 (0.00%)  0 3/9531 (0.03%)  3
Gastroenteritis viral † 1  3/9562 (0.03%)  3 2/9531 (0.02%)  2
Gastrointestinal infection † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Genitourinary tract infection † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Graft infection † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Groin abscess † 1  0/9562 (0.00%)  0 2/9531 (0.02%)  2
H1n1 influenza † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Helicobacter gastritis † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Helicobacter infection † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Hepatitis a † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Hepatitis c † 1  2/9562 (0.02%)  2 0/9531 (0.00%)  0
Hepatitis e † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Herpes ophthalmic † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Herpes virus infection † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Herpes zoster † 1  5/9562 (0.05%)  5 5/9531 (0.05%)  5
Incision site abscess † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Infected bite † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Infected cyst † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Infected dermal cyst † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Infected skin ulcer † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Infection † 1  1/9562 (0.01%)  1 1/9531 (0.01%)  1
Infectious colitis † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Infectious pleural effusion † 1  1/9562 (0.01%)  1 1/9531 (0.01%)  1
Infective exacerbation of bronchiectasis † 1  0/9562 (0.00%)  0 2/9531 (0.02%)  3
Infective exacerbation of chronic obstructive airways disease † 1  1/9562 (0.01%)  2 1/9531 (0.01%)  1
Influenza † 1  8/9562 (0.08%)  8 10/9531 (0.10%)  10
Joint abscess † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Kidney infection † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Labyrinthitis † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Liver abscess † 1  1/9562 (0.01%)  1 2/9531 (0.02%)  2
Localised infection † 1  7/9562 (0.07%)  8 7/9531 (0.07%)  8
Lower respiratory tract infection † 1  4/9562 (0.04%)  4 5/9531 (0.05%)  5
Ludwig angina † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Lung abscess † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Lung infection † 1  10/9562 (0.10%)  12 6/9531 (0.06%)  7
Meningitis † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  2
Meningitis bacterial † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Meningococcal infection † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Necrotising fasciitis † 1  1/9562 (0.01%)  1 1/9531 (0.01%)  1
Neutropenic sepsis † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Oesophageal candidiasis † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Ophthalmic herpes zoster † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Orchitis † 1  5/9562 (0.05%)  5 1/9531 (0.01%)  1
Osteomyelitis † 1  14/9562 (0.15%)  16 7/9531 (0.07%)  8
Osteomyelitis acute † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Osteomyelitis chronic † 1  3/9562 (0.03%)  3 0/9531 (0.00%)  0
Otitis media † 1  1/9562 (0.01%)  1 1/9531 (0.01%)  1
Otitis media acute † 1  2/9562 (0.02%)  2 0/9531 (0.00%)  0
Otitis media chronic † 1  2/9562 (0.02%)  2 0/9531 (0.00%)  0
Pancreas infection † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Papilloma viral infection † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Parainfluenzae virus infection † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Parotitis † 1  2/9562 (0.02%)  2 1/9531 (0.01%)  1
Perineal abscess † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Periodontitis † 1  1/9562 (0.01%)  1 1/9531 (0.01%)  1
Periorbital cellulitis † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Peritonitis † 1  3/9562 (0.03%)  3 2/9531 (0.02%)  2
Peritonitis bacterial † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Peritonsillar abscess † 1  2/9562 (0.02%)  2 1/9531 (0.01%)  1
Pharyngeal abscess † 1  0/9562 (0.00%)  0 2/9531 (0.02%)  2
Pneumocystis jirovecii infection † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Pneumonia † 1  130/9562 (1.36%)  137 147/9531 (1.54%)  153
Pneumonia bacterial † 1  3/9562 (0.03%)  3 3/9531 (0.03%)  3
Pneumonia escherichia † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Pneumonia influenzal † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Pneumonia mycoplasmal † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Pneumonia staphylococcal † 1  1/9562 (0.01%)  1 1/9531 (0.01%)  1
Pneumonia streptococcal † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Pneumonia viral † 1  2/9562 (0.02%)  2 1/9531 (0.01%)  1
Post procedural infection † 1  2/9562 (0.02%)  2 3/9531 (0.03%)  3
Post procedural sepsis † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Postoperative abscess † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Postoperative wound infection † 1  3/9562 (0.03%)  3 7/9531 (0.07%)  7
Prostatic abscess † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Prostatitis escherichia coli † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Pyelonephritis † 1  8/9562 (0.08%)  8 4/9531 (0.04%)  4
Pyelonephritis acute † 1  3/9562 (0.03%)  3 12/9531 (0.13%)  12
Pyelonephritis chronic † 1  0/9562 (0.00%)  0 2/9531 (0.02%)  2
Rectal abscess † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Respiratory tract infection † 1  4/9562 (0.04%)  4 5/9531 (0.05%)  5
Respiratory tract infection viral † 1  2/9562 (0.02%)  2 1/9531 (0.01%)  1
Salmonellosis † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Scrotal abscess † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Sepsis † 1  14/9562 (0.15%)  15 20/9531 (0.21%)  20
Septic shock † 1  7/9562 (0.07%)  7 7/9531 (0.07%)  7
Sinusitis † 1  1/9562 (0.01%)  1 2/9531 (0.02%)  2
Skin infection † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Soft tissue infection † 1  0/9562 (0.00%)  0 2/9531 (0.02%)  2
Staphylococcal infection † 1  1/9562 (0.01%)  1 1/9531 (0.01%)  1
Staphylococcal sepsis † 1  1/9562 (0.01%)  1 1/9531 (0.01%)  1
Streptococcal infection † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Streptococcal sepsis † 1  4/9562 (0.04%)  4 0/9531 (0.00%)  0
Subcutaneous abscess † 1  2/9562 (0.02%)  3 1/9531 (0.01%)  1
Tonsillitis † 1  1/9562 (0.01%)  1 1/9531 (0.01%)  1
Tooth abscess † 1  2/9562 (0.02%)  2 1/9531 (0.01%)  1
Tracheobronchitis † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Tracheobronchitis mycoplasmal † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Tuberculosis † 1  2/9562 (0.02%)  2 0/9531 (0.00%)  0
Tuberculosis of genitourinary system † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Upper respiratory tract infection † 1  3/9562 (0.03%)  3 5/9531 (0.05%)  5
Ureteritis † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Urinary tract infection † 1  33/9562 (0.35%)  37 36/9531 (0.38%)  50
Urinary tract infection bacterial † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Urosepsis † 1  12/9562 (0.13%)  13 10/9531 (0.10%)  11
Vestibular neuronitis † 1  1/9562 (0.01%)  1 1/9531 (0.01%)  1
Viral infection † 1  2/9562 (0.02%)  2 6/9531 (0.06%)  6
Vulval abscess † 1  2/9562 (0.02%)  2 0/9531 (0.00%)  0
Vulval cellulitis † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
West nile viral infection † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Wound infection † 1  5/9562 (0.05%)  5 4/9531 (0.04%)  5
Injury, poisoning and procedural complications     
Abdominal injury † 1  2/9562 (0.02%)  2 0/9531 (0.00%)  0
Accident at home † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Acetabulum fracture † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Adrenal gland injury † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Anaemia postoperative † 1  2/9562 (0.02%)  2 0/9531 (0.00%)  0
Anastomotic leak † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Anastomotic stenosis † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Ankle fracture † 1  8/9562 (0.08%)  8 8/9531 (0.08%)  8
Arterial bypass thrombosis † 1  0/9562 (0.00%)  0 2/9531 (0.02%)  2
Arthropod bite † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Avulsion fracture † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Brain contusion † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Burns third degree † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Carbon monoxide poisoning † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Carotid artery restenosis † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Cataract traumatic † 1  1/9562 (0.01%)  1 1/9531 (0.01%)  1
Cervical vertebral fracture † 1  2/9562 (0.02%)  2 1/9531 (0.01%)  1
Clavicle fracture † 1  1/9562 (0.01%)  1 3/9531 (0.03%)  3
Concussion † 1  2/9562 (0.02%)  2 1/9531 (0.01%)  1
Contusion † 1  7/9562 (0.07%)  7 7/9531 (0.07%)  7
Coronary artery restenosis † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Coronary vascular graft occlusion † 1  1/9562 (0.01%)  1 1/9531 (0.01%)  1
Coronary vascular graft stenosis † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Craniocerebral injury † 1  5/9562 (0.05%)  5 1/9531 (0.01%)  1
Dislocation of sternum † 1  1/9562 (0.01%)  2 0/9531 (0.00%)  0
Epidural haemorrhage † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Extradural haematoma † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Extraskeletal ossification † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Facial bones fracture † 1  1/9562 (0.01%)  1 2/9531 (0.02%)  2
Failure to anastomose † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Fall † 1  5/9562 (0.05%)  5 1/9531 (0.01%)  2
Femoral neck fracture † 1  3/9562 (0.03%)  3 4/9531 (0.04%)  4
Femur fracture † 1  8/9562 (0.08%)  8 15/9531 (0.16%)  15
Fibula fracture † 1  1/9562 (0.01%)  1 1/9531 (0.01%)  1
Foot fracture † 1  2/9562 (0.02%)  2 4/9531 (0.04%)  4
Foreign body † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Foreign body in gastrointestinal tract † 1  1/9562 (0.01%)  1 2/9531 (0.02%)  2
Fracture † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Fractured sacrum † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Hand fracture † 1  1/9562 (0.01%)  1 1/9531 (0.01%)  1
Head injury † 1  8/9562 (0.08%)  8 3/9531 (0.03%)  3
Heat stroke † 1  0/9562 (0.00%)  0 2/9531 (0.02%)  2
Hip fracture † 1  8/9562 (0.08%)  8 9/9531 (0.09%)  9
Humerus fracture † 1  12/9562 (0.13%)  12 8/9531 (0.08%)  8
Hyphaema † 1  1/9562 (0.01%)  1 1/9531 (0.01%)  1
Incisional hernia † 1  1/9562 (0.01%)  1 3/9531 (0.03%)  3
Intervertebral disc injury † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Joint dislocation † 1  2/9562 (0.02%)  2 2/9531 (0.02%)  2
Joint injury † 1  3/9562 (0.03%)  3 4/9531 (0.04%)  4
Ligament injury † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Ligament rupture † 1  4/9562 (0.04%)  4 2/9531 (0.02%)  2
Ligament sprain † 1  1/9562 (0.01%)  1 1/9531 (0.01%)  1
Limb injury † 1  12/9562 (0.13%)  13 7/9531 (0.07%)  8
Lower limb fracture † 1  2/9562 (0.02%)  2 2/9531 (0.02%)  2
Lumbar vertebral fracture † 1  1/9562 (0.01%)  1 2/9531 (0.02%)  2
Lumbosacral plexus injury † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Median nerve injury † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Meniscus injury † 1  9/9562 (0.09%)  9 5/9531 (0.05%)  5
Multiple fractures † 1  3/9562 (0.03%)  3 1/9531 (0.01%)  1
Multiple injuries † 1  1/9562 (0.01%)  1 1/9531 (0.01%)  1
Muscle injury † 1  0/9562 (0.00%)  0 2/9531 (0.02%)  2
Muscle strain † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Nail injury † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Nerve injury † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Nerve root injury † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Nerve root injury lumbar † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Overdose † 1  1/9562 (0.01%)  2 0/9531 (0.00%)  0
Patella fracture † 1  2/9562 (0.02%)  2 2/9531 (0.02%)  2
Pelvic fracture † 1  3/9562 (0.03%)  3 1/9531 (0.01%)  1
Periorbital haemorrhage † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Periprocedural myocardial infarction † 1  0/9562 (0.00%)  0 2/9531 (0.02%)  2
Post procedural complication † 1  1/9562 (0.01%)  1 2/9531 (0.02%)  2
Post procedural fever † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Post procedural haematoma † 1  4/9562 (0.04%)  4 1/9531 (0.01%)  1
Post procedural haemorrhage † 1  11/9562 (0.12%)  11 5/9531 (0.05%)  5
Postoperative ileus † 1  2/9562 (0.02%)  2 0/9531 (0.00%)  0
Postoperative respiratory failure † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Postoperative thoracic procedure complication † 1  2/9562 (0.02%)  2 0/9531 (0.00%)  0
Procedural complication † 1  2/9562 (0.02%)  2 0/9531 (0.00%)  0
Procedural haemorrhage † 1  2/9562 (0.02%)  2 3/9531 (0.03%)  3
Procedural pain † 1  1/9562 (0.01%)  1 2/9531 (0.02%)  2
Pubis fracture † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Pulmonary contusion † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Radiation pneumonitis † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Radius fracture † 1  6/9562 (0.06%)  7 8/9531 (0.08%)  8
Rib fracture † 1  4/9562 (0.04%)  4 10/9531 (0.10%)  10
Road traffic accident † 1  1/9562 (0.01%)  1 2/9531 (0.02%)  2
Scapula fracture † 1  0/9562 (0.00%)  0 2/9531 (0.02%)  2
Seroma † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Shunt malfunction † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Skeletal injury † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Skin abrasion † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Skin injury † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Skin laceration † 1  2/9562 (0.02%)  2 6/9531 (0.06%)  6
Skull fracture † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Skull fractured base † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Spinal column injury † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Spinal compression fracture † 1  0/9562 (0.00%)  0 7/9531 (0.07%)  7
Spinal cord injury cervical † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Spinal fracture † 1  1/9562 (0.01%)  1 1/9531 (0.01%)  1
Sternal fracture † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Stomal hernia † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Subcutaneous haematoma † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Subdural haematoma † 1  23/9562 (0.24%)  23 6/9531 (0.06%)  6
Subdural haemorrhage † 1  8/9562 (0.08%)  8 5/9531 (0.05%)  5
Tendon injury † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Tendon rupture † 1  2/9562 (0.02%)  2 8/9531 (0.08%)  8
Thermal burn † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Thoracic vertebral fracture † 1  0/9562 (0.00%)  0 2/9531 (0.02%)  2
Tibia fracture † 1  3/9562 (0.03%)  3 6/9531 (0.06%)  6
Toxicity to various agents † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Traumatic fracture † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Traumatic haematoma † 1  7/9562 (0.07%)  7 2/9531 (0.02%)  2
Traumatic haemorrhage † 1  2/9562 (0.02%)  2 1/9531 (0.01%)  1
Traumatic haemothorax † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Traumatic intracranial haemorrhage † 1  11/9562 (0.12%)  11 7/9531 (0.07%)  7
Ulna fracture † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Upper limb fracture † 1  6/9562 (0.06%)  6 0/9531 (0.00%)  0
Urinary retention postoperative † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Vascular graft complication † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Vascular graft thrombosis † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Vascular pseudoaneurysm † 1  2/9562 (0.02%)  2 0/9531 (0.00%)  0
Wound † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Wound dehiscence † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Wound haemorrhage † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Wound necrosis † 1  0/9562 (0.00%)  0 3/9531 (0.03%)  3
Wrist fracture † 1  2/9562 (0.02%)  2 3/9531 (0.03%)  3
Investigations     
Alanine aminotransferase increased † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Bile output decreased † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Blood follicle stimulating hormone increased † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Blood glucose fluctuation † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Blood glucose increased † 1  5/9562 (0.05%)  5 3/9531 (0.03%)  3
Blood lactic acid increased † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Blood potassium increased † 1  0/9562 (0.00%)  0 2/9531 (0.02%)  3
Blood pressure increased † 1  2/9562 (0.02%)  2 0/9531 (0.00%)  0
Blood urine present † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Cardiac stress test abnormal † 1  3/9562 (0.03%)  3 4/9531 (0.04%)  4
Electrocardiogram qrs complex prolonged † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Electrocardiogram st segment depression † 1  1/9562 (0.01%)  2 0/9531 (0.00%)  0
Electrocardiogram abnormal † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Glycosylated haemoglobin increased † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Haemoglobin decreased † 1  2/9562 (0.02%)  2 3/9531 (0.03%)  3
Heart rate irregular † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Hepatic enzyme increased † 1  1/9562 (0.01%)  1 1/9531 (0.01%)  1
Hepatitis b surface antigen positive † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Occult blood positive † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Oxygen saturation decreased † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Prostatic specific antigen increased † 1  2/9562 (0.02%)  2 0/9531 (0.00%)  0
Troponin increased † 1  1/9562 (0.01%)  1 2/9531 (0.02%)  2
Weight decreased † 1  2/9562 (0.02%)  2 1/9531 (0.01%)  1
White blood cell count decreased † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Metabolism and nutrition disorders     
Decreased appetite † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Dehydration † 1  6/9562 (0.06%)  7 5/9531 (0.05%)  5
Diabetes mellitus † 1  24/9562 (0.25%)  28 42/9531 (0.44%)  46
Diabetes mellitus inadequate control † 1  50/9562 (0.52%)  55 60/9531 (0.63%)  78
Diabetic complication † 1  0/9562 (0.00%)  0 2/9531 (0.02%)  2
Diabetic ketoacidosis † 1  10/9562 (0.10%)  11 11/9531 (0.12%)  13
Diabetic metabolic decompensation † 1  9/9562 (0.09%)  9 17/9531 (0.18%)  17
Euglycaemic diabetic ketoacidosis † 1  0/9562 (0.00%)  0 1/9531 (0.01%)  1
Fluid overload † 1  2/9562 (0.02%)  2 1/9531 (0.01%)  2
Gout † 1  5/9562 (0.05%)  7 6/9531 (0.06%)  6
Hypercalcaemia † 1  1/9562 (0.01%)  1 0/9531 (0.00%)  0
Hyperglycaemia † 1  20/9562 (0.21%)  21