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A Study of Vericiguat in Participants With Heart Failure With Reduced Ejection Fraction (HFrEF) (MK-1242-001) (VICTORIA)

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: NCT02861534
Recruitment Status : Completed
First Posted : August 10, 2016
Results First Posted : June 29, 2020
Last Update Posted : July 14, 2020
Sponsor:
Collaborators:
Bayer
Canadian VIGOUR Centre
Duke Clinical Research Institute
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Conditions Heart Failure
Chronic Heart Failure With Reduced Ejection Fraction
Interventions Drug: Vericiguat
Drug: Placebo for vericiguat
Enrollment 5050
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Vericiguat Placebo
Hide Arm/Group Description Participants received a starting dose of 2.5 mg of vericiguat taken orally once daily with food, on a background of heart failure (HF) standard of care. The vericiguat dose was uptitrated to 5 mg and to 10 mg. Participants received a starting matching placebo dose of 2.5 mg taken orally once daily with food, on a background of HF standard of care. The matching placebo dose was uptitrated to 5 mg and to 10 mg.
Period Title: Overall Study
Started 2526 2524
Treated 2519 2515
Completed 1952 1937
Not Completed 574 587
Reason Not Completed
Death             541             552
Lost to Follow-up             14             14
Site Terminated by Sponsor             4             3
Withdrawal by Subject             15             18
Arm/Group Title Vericiguat Placebo Total
Hide Arm/Group Description Participants received a starting dose of 2.5 mg of vericiguat taken orally once daily with food, on a background of heart failure (HF) standard of care. The vericiguat dose was uptitrated to 5 mg and to 10 mg. Participants received a starting matching placebo dose of 2.5 mg taken orally once daily with food, on a background of HF standard of care. The matching placebo dose was uptitrated to 5 mg and to 10 mg. Total of all reporting groups
Overall Number of Baseline Participants 2526 2524 5050
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 2526 participants 2524 participants 5050 participants
67.5  (12.2) 67.2  (12.2) 67.3  (12.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2526 participants 2524 participants 5050 participants
Female
605
  24.0%
603
  23.9%
1208
  23.9%
Male
1921
  76.0%
1921
  76.1%
3842
  76.1%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2526 participants 2524 participants 5050 participants
American Indian or Alaska Native
24
   1.0%
28
   1.1%
52
   1.0%
Asian
571
  22.6%
561
  22.2%
1132
  22.4%
Native Hawaiian or Other Pacific Islander
3
   0.1%
11
   0.4%
14
   0.3%
Black or African American
123
   4.9%
126
   5.0%
249
   4.9%
White
1621
  64.2%
1618
  64.1%
3239
  64.1%
More than one race
183
   7.2%
180
   7.1%
363
   7.2%
Unknown or Not Reported
1
   0.0%
0
   0.0%
1
   0.0%
1.Primary Outcome
Title Time to First Occurrence of Composite Endpoint of Cardiovascular (CV) Death or Heart Failure (HF) Hospitalization
Hide Description Time to First Occurrence of Composite Endpoint of CV Death or HF Hospitalization was analyzed using a one-sided stratified log-rank test. Randomized participants without any HF hospitalization or CV death event at the time of analysis were censored at their last available information, the date of their non-CV death, or the primary analysis database cutoff date of 18-June-2019, whichever occurred first. A clinical events committee (CEC) reviewed and adjudicated the endpoint events. A time-to-event methodology was used to evaluate the results; the incidence rate of participants with an event (number of participants with an event per 100 participant-years at risk) is provided.
Time Frame Up to approximately 33 months (through primary analysis database cutoff date of 18-June-2019)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants
Arm/Group Title Vericiguat Placebo
Hide Arm/Group Description:
Participants received a starting dose of 2.5 mg of vericiguat taken orally once daily with food, on a background of HF standard of care. The vericiguat dose was uptitrated to 5 mg and to 10 mg.
Participants received a starting matching placebo dose of 2.5 mg taken orally once daily with food, on a background of HF standard of care. The matching placebo dose was uptitrated to 5 mg and to 10 mg.
Overall Number of Participants Analyzed 2526 2524
Measure Type: Number
Unit of Measure: Parts w/ event per 100 part-yrs at risk
33.6 37.8
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vericiguat, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.019
Comments [Not Specified]
Method Cox proportional hazard model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.90
Confidence Interval (2-Sided) 95%
0.82 to 0.98
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Time to the First Occurrence of CV Death
Hide Description Time to First Occurrence of CV Death was analyzed using a one-sided stratified log-rank test. Randomized participants without a CV death at the time of analysis were censored at their last available information, the date of their non-CV death, or the primary analysis database cutoff date of 18-June-2019, whichever occurred first. A CEC reviewed and adjudicated the endpoint events. A time-to-event methodology was used to evaluate the results; the incidence rate of participants with an event (number of participants with an event per 100 participant-years at risk) is provided.
Time Frame Up to approximately 33 months (through primary analysis database cutoff date of 18-June-2019)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants
Arm/Group Title Vericiguat Placebo
Hide Arm/Group Description:
Participants received a starting dose of 2.5 mg of vericiguat taken orally once daily with food, on a background of HF standard of care. The vericiguat dose was uptitrated to 5 mg and to 10 mg.
Participants received a starting matching placebo dose of 2.5 mg taken orally once daily with food, on a background of HF standard of care. The matching placebo dose was uptitrated to 5 mg and to 10 mg.
Overall Number of Participants Analyzed 2526 2524
Measure Type: Number
Unit of Measure: Parts w/ event per 100 part-yrs at risk
12.9 13.9
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vericiguat, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.269
Comments [Not Specified]
Method Cox proportional hazard model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.93
Confidence Interval (2-Sided) 95%
0.81 to 1.06
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Time to the First Occurrence of HF Hospitalization
Hide Description Time to the First Occurrence of HF Hospitalization was analyzed using a one-sided stratified log-rank test. Randomized participants without any HF hospitalization at the time of analysis were censored at their last available information, the date of their death, or the primary analysis database cutoff date of 18-June-2019, whichever occurred first. A CEC reviewed and adjudicated the endpoint events. A time-to-event methodology was used to evaluate the results; the incidence rate of participants with an event (number of participants with an event per 100 participant-years at risk) is provided.
Time Frame Up to approximately 33 months (through primary analysis database cutoff date of 18-June-2019)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants
Arm/Group Title Vericiguat Placebo
Hide Arm/Group Description:
Participants received a starting dose of 2.5 mg of vericiguat taken orally once daily with food, on a background of HF standard of care. The vericiguat dose was uptitrated to 5 mg and to 10 mg.
Participants received a starting matching placebo dose of 2.5 mg taken orally once daily with food, on a background of HF standard of care. The matching placebo dose was uptitrated to 5 mg and to 10 mg.
Overall Number of Participants Analyzed 2526 2524
Measure Type: Number
Unit of Measure: Parts w/ event per 100 part-yrs at risk
25.9 29.1
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vericiguat, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.048
Comments [Not Specified]
Method Cox proportional hazard model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.90
Confidence Interval (2-Sided) 95%
0.81 to 1.00
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Time to Total HF Hospitalizations (Including First and Recurrent Events)
Hide Description Time to Total HF Hospitalizations (including first and recurring) was analyzed using an Andersen-Gill model. Randomized participants without any HF hospitalization at the time of analysis were censored at their last available information, the date of their death, or the primary analysis database cutoff date of 18-June-2019, whichever occurred first. A CEC reviewed and adjudicated the endpoint events. A time-to-event methodology was used to evaluate the results; the incidence rate of participants with an event (number of participants with an event per 100 participant-years of follow-up) is provided.
Time Frame Up to approximately 33 months (through primary analysis database cutoff date of 18-June-2019)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants
Arm/Group Title Vericiguat Placebo
Hide Arm/Group Description:
Participants received a starting dose of 2.5 mg of vericiguat taken orally once daily with food, on a background of HF standard of care. The vericiguat dose was uptitrated to 5 mg and to 10 mg.
Participants received a starting matching placebo dose of 2.5 mg taken orally once daily with food, on a background of HF standard of care. The matching placebo dose was uptitrated to 5 mg and to 10 mg.
Overall Number of Participants Analyzed 2526 2524
Measure Type: Number
Unit of Measure: Parts w/ event per 100 part-yrs
38.3 42.4
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vericiguat, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.023
Comments [Not Specified]
Method Andersen-Gill model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.91
Confidence Interval (2-Sided) 95%
0.84 to 0.99
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Time to First Occurrence of Composite Endpoint of All-Cause Mortality or HF Hospitalization
Hide Description Time to First Occurrence of Composite Endpoint of All-Cause Mortality or HF Hospitalization was analyzed using a one-sided stratified log-rank test. Randomized participants without any all-cause mortality event or HF hospitalization at the time of analysis were censored at their last available information or the primary analysis database cutoff date of 18-June-2019, whichever occurred first. A CEC reviewed and adjudicated the endpoint events. A time-to-event methodology was used to evaluate the results; the incidence rate of participants with an event (number of participants with an event per 100 participant-years at risk) is provided.
Time Frame Up to approximately 33 months (through primary analysis database cutoff date of 18-June-2019)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants
Arm/Group Title Vericiguat Placebo
Hide Arm/Group Description:
Participants received a starting dose of 2.5 mg of vericiguat taken orally once daily with food, on a background of HF standard of care. The vericiguat dose was uptitrated to 5 mg and to 10 mg.
Participants received a starting matching placebo dose of 2.5 mg taken orally once daily with food, on a background of HF standard of care. The matching placebo dose was uptitrated to 5 mg and to 10 mg.
Overall Number of Participants Analyzed 2526 2524
Measure Type: Number
Unit of Measure: Parts w/ event per 100 part-yrs at risk
35.9 40.1
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vericiguat, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.021
Comments [Not Specified]
Method Cox proportional hazard model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.90
Confidence Interval (2-Sided) 95%
0.83 to 0.98
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Time to All-Cause Mortality
Hide Description Time to All-Cause Mortality was analyzed using a one-sided stratified log-rank test. Randomized participants without any all-cause mortality event at the time of analysis were censored at their last available information or the primary analysis database cutoff date of 18-June-2019, whichever occurred first. A CEC reviewed and adjudicated the endpoint events. A time-to-event methodology was used to evaluate the results: the incidence rate of participants with an event (number of participants with an event per 100 participant-years at risk) is provided.
Time Frame Up to approximately 33 months (through primary analysis database cutoff date of 18-June-2019)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants
Arm/Group Title Vericiguat Placebo
Hide Arm/Group Description:
Participants received a starting dose of 2.5 mg of vericiguat taken orally once daily with food, on a background of HF standard of care. The vericiguat dose was uptitrated to 5 mg and to 10 mg.
Participants received a starting matching placebo dose of 2.5 mg taken orally once daily with food, on a background of HF standard of care. The matching placebo dose was uptitrated to 5 mg and to 10 mg.
Overall Number of Participants Analyzed 2526 2524
Measure Type: Number
Unit of Measure: Parts w/ event per 100 part-yrs at risk
16.0 16.9
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vericiguat, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.377
Comments [Not Specified]
Method Cox proportional hazard model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.95
Confidence Interval (2-Sided) 95%
0.84 to 1.07
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Number of Participants Who Experienced One or More Adverse Events
Hide Description An adverse event (AE) is any untoward medical occurrence in a study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.
Time Frame Up to approximately 33 months (through primary analysis database cutoff date of 18-June-2019)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study treatment
Arm/Group Title Vericiguat Placebo
Hide Arm/Group Description:
Participants received a starting dose of 2.5 mg of vericiguat taken orally once daily with food, on a background of HF standard of care. The vericiguat dose was uptitrated to 5 mg and to 10 mg.
Participants received a starting matching placebo dose of 2.5 mg taken orally once daily with food, on a background of HF standard of care. The matching placebo dose was uptitrated to 5 mg and to 10 mg.
Overall Number of Participants Analyzed 2519 2515
Measure Type: Count of Participants
Unit of Measure: Participants
2027
  80.5%
2036
  81.0%
8.Secondary Outcome
Title Number of Participants Who Discontinued Treatment Due to an Adverse Event
Hide Description An adverse event (AE) is any untoward medical occurrence in a study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.
Time Frame Up to approximately 33 months (through primary analysis database cutoff date of 18-June-2019)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study treatment
Arm/Group Title Vericiguat Placebo
Hide Arm/Group Description:
Participants received a starting dose of 2.5 mg of vericiguat taken orally once daily with food, on a background of HF standard of care. The vericiguat dose was uptitrated to 5 mg and to 10 mg.
Participants received a starting matching placebo dose of 2.5 mg taken orally once daily with food, on a background of HF standard of care. The matching placebo dose was uptitrated to 5 mg and to 10 mg.
Overall Number of Participants Analyzed 2519 2515
Measure Type: Count of Participants
Unit of Measure: Participants
167
   6.6%
158
   6.3%
9.Secondary Outcome
Title Percentage of Participants Who Experienced Symptomatic Hypotension
Hide Description Study participants were monitored for symptomatic hypotension, an event of clinical interest, and results were reported.
Time Frame Up to approximately 33 months (through primary analysis database cutoff date of 18-June-2019)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study treatment
Arm/Group Title Vericiguat Placebo
Hide Arm/Group Description:
Participants received a starting dose of 2.5 mg of vericiguat taken orally once daily with food, on a background of HF standard of care. The vericiguat dose was uptitrated to 5 mg and to 10 mg.
Participants received a starting matching placebo dose of 2.5 mg taken orally once daily with food, on a background of HF standard of care. The matching placebo dose was uptitrated to 5 mg and to 10 mg.
Overall Number of Participants Analyzed 2519 2515
Measure Type: Number
Unit of Measure: Percentage of participants
9.1 7.9
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vericiguat, Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.121
Comments [Not Specified]
Method Miettinen & Nurminen method
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percentage
Estimated Value 1.2
Confidence Interval (2-Sided) 95%
-0.3 to 2.8
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Percentage of Participants Who Experienced Syncope
Hide Description Study participants were monitored for syncope, an event of clinical interest, and results were reported.
Time Frame Up to approximately 33 months (through primary analysis database cutoff date of 18-June-2019)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study treatment
Arm/Group Title Vericiguat Placebo
Hide Arm/Group Description:
Participants received a starting dose of 2.5 mg of vericiguat taken orally once daily with food, on a background of HF standard of care. The vericiguat dose was uptitrated to 5 mg and to 10 mg.
Participants received a starting matching placebo dose of 2.5 mg taken orally once daily with food, on a background of HF standard of care. The matching placebo dose was uptitrated to 5 mg and to 10 mg.
Overall Number of Participants Analyzed 2519 2515
Measure Type: Number
Unit of Measure: Percentage of participants
4.0 3.5
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vericiguat, Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.303
Comments [Not Specified]
Method Miettinen & Nurminen method
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percentage
Estimated Value 0.6
Confidence Interval (2-Sided) 95%
-0.5 to 1.6
Estimation Comments [Not Specified]
Time Frame Up to approximately 35 months (through Last Subject Last Visit date of 02-Sept-2019)
Adverse Event Reporting Description

Serious Adverse Events and Other Adverse Events: All randomized participants who received at least 1 dose of study treatment

All-Cause Mortality: All randomized participants

 
Arm/Group Title Vericiguat Placebo
Hide Arm/Group Description Participants received a starting dose of 2.5 mg of vericiguat taken orally once daily with food, on a background of HF standard of care. The vericiguat dose was uptitrated to 5 mg and to 10 mg. Participants received a starting matching placebo dose of 2.5 mg taken orally once daily with food, on a background of HF standard of care. The matching placebo dose was uptitrated to 5 mg and to 10 mg.
All-Cause Mortality
Vericiguat Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   553/2526 (21.89%)      561/2524 (22.23%)    
Hide Serious Adverse Events
Vericiguat Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   852/2519 (33.82%)      897/2515 (35.67%)    
Blood and lymphatic system disorders     
Anaemia  1  41/2519 (1.63%)  50 24/2515 (0.95%)  25
Anaemia of chronic disease  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Autoimmune haemolytic anaemia  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Bicytopenia  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Blood loss anaemia  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Bone marrow failure  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Coagulopathy  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Disseminated intravascular coagulation  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Hypocoagulable state  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Iron deficiency anaemia  1  3/2519 (0.12%)  3 2/2515 (0.08%)  2
Normochromic normocytic anaemia  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Normocytic anaemia  1  1/2519 (0.04%)  1 1/2515 (0.04%)  1
Pancytopenia  1  3/2519 (0.12%)  3 1/2515 (0.04%)  1
Splenic infarction  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Thrombocytopenia  1  2/2519 (0.08%)  2 1/2515 (0.04%)  1
Cardiac disorders     
Acute coronary syndrome  1  1/2519 (0.04%)  1 4/2515 (0.16%)  4
Acute myocardial infarction  1  5/2519 (0.20%)  6 5/2515 (0.20%)  5
Angina pectoris  1  9/2519 (0.36%)  10 8/2515 (0.32%)  9
Angina unstable  1  2/2519 (0.08%)  2 7/2515 (0.28%)  13
Aortic valve calcification  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Aortic valve incompetence  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Aortic valve stenosis  1  3/2519 (0.12%)  3 3/2515 (0.12%)  3
Arrhythmia  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Arteriosclerosis coronary artery  1  2/2519 (0.08%)  2 0/2515 (0.00%)  0
Atrial fibrillation  1  14/2519 (0.56%)  15 29/2515 (1.15%)  31
Atrial flutter  1  6/2519 (0.24%)  7 7/2515 (0.28%)  7
Atrial tachycardia  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Atrial thrombosis  1  0/2519 (0.00%)  0 2/2515 (0.08%)  2
Atrioventricular block  1  2/2519 (0.08%)  2 0/2515 (0.00%)  0
Atrioventricular block complete  1  0/2519 (0.00%)  0 2/2515 (0.08%)  2
Atrioventricular block second degree  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Bradyarrhythmia  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Bradycardia  1  3/2519 (0.12%)  3 3/2515 (0.12%)  3
Bundle branch block left  1  0/2519 (0.00%)  0 2/2515 (0.08%)  2
Cardiac arrest  1  3/2519 (0.12%)  3 3/2515 (0.12%)  3
Cardiac asthma  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Cardiac failure  1  82/2519 (3.26%)  88 116/2515 (4.61%)  128
Cardiac failure acute  1  2/2519 (0.08%)  2 4/2515 (0.16%)  4
Cardiac failure chronic  1  5/2519 (0.20%)  5 10/2515 (0.40%)  10
Cardiac failure congestive  1  13/2519 (0.52%)  13 25/2515 (0.99%)  25
Cardiac perforation  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Cardiac ventricular thrombosis  1  2/2519 (0.08%)  2 0/2515 (0.00%)  0
Cardio-respiratory arrest  1  4/2519 (0.16%)  4 1/2515 (0.04%)  1
Cardiogenic shock  1  8/2519 (0.32%)  8 4/2515 (0.16%)  4
Cardiopulmonary failure  1  1/2519 (0.04%)  1 1/2515 (0.04%)  1
Cardiorenal syndrome  1  3/2519 (0.12%)  3 2/2515 (0.08%)  2
Cardiovascular disorder  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Cardiovascular insufficiency  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Congestive cardiomyopathy  1  3/2519 (0.12%)  3 3/2515 (0.12%)  3
Coronary artery disease  1  7/2519 (0.28%)  8 3/2515 (0.12%)  3
Coronary artery occlusion  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Coronary artery stenosis  1  3/2519 (0.12%)  4 2/2515 (0.08%)  2
Extrasystoles  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Heart valve incompetence  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Intracardiac thrombus  1  0/2519 (0.00%)  0 2/2515 (0.08%)  2
Ischaemic cardiomyopathy  1  1/2519 (0.04%)  1 2/2515 (0.08%)  2
Left ventricular dysfunction  1  1/2519 (0.04%)  1 1/2515 (0.04%)  1
Left ventricular failure  1  0/2519 (0.00%)  0 2/2515 (0.08%)  2
Mitral valve incompetence  1  7/2519 (0.28%)  7 5/2515 (0.20%)  5
Myocardial infarction  1  6/2519 (0.24%)  6 3/2515 (0.12%)  3
Myocardial ischaemia  1  3/2519 (0.12%)  3 2/2515 (0.08%)  2
Palpitations  1  2/2519 (0.08%)  2 1/2515 (0.04%)  1
Pericardial effusion  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Pericarditis  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Sinus bradycardia  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Sinus node dysfunction  1  2/2519 (0.08%)  2 2/2515 (0.08%)  2
Supraventricular tachycardia  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Tachyarrhythmia  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Tachycardia  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Ventricular arrhythmia  1  2/2519 (0.08%)  2 1/2515 (0.04%)  1
Ventricular dysfunction  1  0/2519 (0.00%)  0 2/2515 (0.08%)  2
Ventricular extrasystoles  1  2/2519 (0.08%)  2 2/2515 (0.08%)  2
Ventricular fibrillation  1  9/2519 (0.36%)  10 7/2515 (0.28%)  9
Ventricular tachycardia  1  14/2519 (0.56%)  18 27/2515 (1.07%)  29
Congenital, familial and genetic disorders     
Corneal dystrophy  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Gastrointestinal arteriovenous malformation  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Hydrocele  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Phimosis  1  1/2519 (0.04%)  1 1/2515 (0.04%)  1
Pyloric stenosis  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Ear and labyrinth disorders     
Vertigo  1  3/2519 (0.12%)  3 7/2515 (0.28%)  7
Vertigo positional  1  1/2519 (0.04%)  1 3/2515 (0.12%)  4
Endocrine disorders     
Basedow's disease  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Carcinoid syndrome  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Glucocorticoid deficiency  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Hyperthyroidism  1  4/2519 (0.16%)  4 1/2515 (0.04%)  1
Hypoparathyroidism secondary  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Hypothyroidism  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Eye disorders     
Blindness  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Cataract  1  9/2519 (0.36%)  10 6/2515 (0.24%)  8
Diabetic retinopathy  1  2/2519 (0.08%)  2 1/2515 (0.04%)  1
Diplopia  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Eye haemorrhage  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Eyelid ptosis  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Glaucoma  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Macular cyst  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Retinal artery thrombosis  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Retinal haemorrhage  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Vitreous haemorrhage  1  2/2519 (0.08%)  2 1/2515 (0.04%)  1
Gastrointestinal disorders     
Abdominal distension  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Abdominal pain  1  4/2519 (0.16%)  4 4/2515 (0.16%)  4
Abdominal pain lower  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Abdominal pain upper  1  4/2519 (0.16%)  5 3/2515 (0.12%)  3
Abdominal rigidity  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Alcoholic pancreatitis  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Anorectal ulcer  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Ascites  1  8/2519 (0.32%)  10 4/2515 (0.16%)  5
Barrett's oesophagus  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Colitis  1  2/2519 (0.08%)  2 2/2515 (0.08%)  2
Colitis ischaemic  1  1/2519 (0.04%)  1 1/2515 (0.04%)  1
Constipation  1  3/2519 (0.12%)  3 2/2515 (0.08%)  2
Dental caries  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Dental cyst  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Diarrhoea  1  10/2519 (0.40%)  10 7/2515 (0.28%)  7
Diverticulum  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Diverticulum intestinal  1  1/2519 (0.04%)  1 1/2515 (0.04%)  1
Duodenal ulcer  1  0/2519 (0.00%)  0 3/2515 (0.12%)  3
Erosive oesophagitis  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Faecaloma  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Gastric haemorrhage  1  2/2519 (0.08%)  2 0/2515 (0.00%)  0
Gastric perforation  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Gastric ulcer  1  1/2519 (0.04%)  1 2/2515 (0.08%)  2
Gastric ulcer haemorrhage  1  1/2519 (0.04%)  1 2/2515 (0.08%)  2
Gastritis  1  4/2519 (0.16%)  4 7/2515 (0.28%)  7
Gastritis erosive  1  1/2519 (0.04%)  1 2/2515 (0.08%)  2
Gastritis haemorrhagic  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Gastrointestinal angiodysplasia  1  1/2519 (0.04%)  1 2/2515 (0.08%)  2
Gastrointestinal haemorrhage  1  12/2519 (0.48%)  14 7/2515 (0.28%)  7
Gastrointestinal toxicity  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Gastrooesophageal reflux disease  1  0/2519 (0.00%)  0 4/2515 (0.16%)  4
Gingival bleeding  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Haematemesis  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Haematochezia  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Haemorrhoidal haemorrhage  1  1/2519 (0.04%)  1 1/2515 (0.04%)  1
Haemorrhoids  1  3/2519 (0.12%)  3 2/2515 (0.08%)  2
Ileus  1  2/2519 (0.08%)  2 0/2515 (0.00%)  0
Impaired gastric emptying  1  2/2519 (0.08%)  2 0/2515 (0.00%)  0
Incarcerated inguinal hernia  1  0/2519 (0.00%)  0 3/2515 (0.12%)  3
Incarcerated umbilical hernia  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Inguinal hernia  1  11/2519 (0.44%)  11 9/2515 (0.36%)  9
Inguinal hernia strangulated  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Inguinal hernia, obstructive  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Intestinal infarction  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Intestinal ischaemia  1  1/2519 (0.04%)  1 2/2515 (0.08%)  2
Intestinal obstruction  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Intra-abdominal haematoma  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Ischaemic enteritis  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Large intestinal haemorrhage  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Large intestinal obstruction  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Large intestinal stenosis  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Large intestinal ulcer  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Large intestinal ulcer haemorrhage  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Large intestinal ulcer perforation  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Large intestine polyp  1  1/2519 (0.04%)  2 4/2515 (0.16%)  4
Lower gastrointestinal haemorrhage  1  1/2519 (0.04%)  1 1/2515 (0.04%)  1
Melaena  1  1/2519 (0.04%)  1 2/2515 (0.08%)  2
Nausea  1  2/2519 (0.08%)  2 0/2515 (0.00%)  0
Obstructive pancreatitis  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Oesophageal achalasia  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Oesophageal stenosis  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Oesophageal varices haemorrhage  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Pancreatitis  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Pancreatitis acute  1  2/2519 (0.08%)  2 1/2515 (0.04%)  1
Pancreatitis chronic  1  1/2519 (0.04%)  1 1/2515 (0.04%)  1
Pancreatolithiasis  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Peptic ulcer  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Pneumatosis intestinalis  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Rectal haemorrhage  1  4/2519 (0.16%)  4 1/2515 (0.04%)  1
Small intestinal obstruction  1  2/2519 (0.08%)  2 0/2515 (0.00%)  0
Subileus  1  0/2519 (0.00%)  0 2/2515 (0.08%)  2
Umbilical hernia  1  2/2519 (0.08%)  2 0/2515 (0.00%)  0
Upper gastrointestinal haemorrhage  1  3/2519 (0.12%)  3 6/2515 (0.24%)  6
Vomiting  1  4/2519 (0.16%)  4 2/2515 (0.08%)  2
General disorders     
Asthenia  1  6/2519 (0.24%)  6 6/2515 (0.24%)  7
Cardiac complication associated with device  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Chest discomfort  1  1/2519 (0.04%)  1 2/2515 (0.08%)  2
Chest pain  1  10/2519 (0.40%)  10 8/2515 (0.32%)  14
Device related thrombosis  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Discomfort  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
General physical health deterioration  1  6/2519 (0.24%)  6 1/2515 (0.04%)  1
Generalised oedema  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Hernia  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Impaired healing  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Implant site erythema  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Implant site haematoma  1  2/2519 (0.08%)  2 0/2515 (0.00%)  0
Implant site haemorrhage  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Influenza like illness  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Medical device pain  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Medical device site haematoma  1  2/2519 (0.08%)  2 0/2515 (0.00%)  0
Medical device site swelling  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Medical device site thrombosis  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Multiple organ dysfunction syndrome  1  2/2519 (0.08%)  2 4/2515 (0.16%)  4
Non-cardiac chest pain  1  4/2519 (0.16%)  4 7/2515 (0.28%)  7
Oedema  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Oedema peripheral  1  0/2519 (0.00%)  0 3/2515 (0.12%)  3
Physical deconditioning  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Pyrexia  1  3/2519 (0.12%)  3 2/2515 (0.08%)  2
Sensation of foreign body  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Strangulated hernia  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Sudden cardiac death  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
UGT1A1 gene polymorphism  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Vascular stent occlusion  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Vascular stent stenosis  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Vascular stent thrombosis  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Hepatobiliary disorders     
Acute hepatic failure  1  1/2519 (0.04%)  1 3/2515 (0.12%)  3
Bile duct stone  1  2/2519 (0.08%)  2 1/2515 (0.04%)  1
Biloma  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Cholangitis  1  1/2519 (0.04%)  1 1/2515 (0.04%)  1
Cholangitis acute  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Cholecystitis  1  4/2519 (0.16%)  4 4/2515 (0.16%)  4
Cholecystitis acute  1  4/2519 (0.16%)  4 6/2515 (0.24%)  6
Cholecystitis chronic  1  2/2519 (0.08%)  2 0/2515 (0.00%)  0
Cholelithiasis  1  4/2519 (0.16%)  4 2/2515 (0.08%)  2
Cholestasis  1  1/2519 (0.04%)  1 1/2515 (0.04%)  1
Chronic hepatic failure  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Hepatic cirrhosis  1  2/2519 (0.08%)  2 1/2515 (0.04%)  1
Hepatic congestion  1  4/2519 (0.16%)  4 0/2515 (0.00%)  0
Hepatic failure  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Hepatitis acute  1  1/2519 (0.04%)  1 1/2515 (0.04%)  1
Hepatitis toxic  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Hepatocellular injury  1  2/2519 (0.08%)  2 0/2515 (0.00%)  0
Ischaemic hepatitis  1  4/2519 (0.16%)  4 2/2515 (0.08%)  2
Jaundice cholestatic  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Liver disorder  1  2/2519 (0.08%)  2 0/2515 (0.00%)  0
Liver injury  1  5/2519 (0.20%)  5 2/2515 (0.08%)  2
Portosplenomesenteric venous thrombosis  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Immune system disorders     
Amyloidosis  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Infections and infestations     
Abscess limb  1  3/2519 (0.12%)  3 2/2515 (0.08%)  2
Acinetobacter bacteraemia  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Amoebic dysentery  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Anal abscess  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Appendicitis  1  2/2519 (0.08%)  2 1/2515 (0.04%)  1
Arteriovenous fistula site infection  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Atypical pneumonia  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Bacteraemia  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Bacterial sepsis  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Bronchitis  1  10/2519 (0.40%)  10 7/2515 (0.28%)  7
Bronchitis viral  1  2/2519 (0.08%)  2 1/2515 (0.04%)  1
Campylobacter gastroenteritis  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Cellulitis  1  25/2519 (0.99%)  27 19/2515 (0.76%)  20
Cellulitis gangrenous  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Chest wall abscess  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Cholecystitis infective  1  0/2519 (0.00%)  0 2/2515 (0.08%)  2
Chronic sinusitis  1  1/2519 (0.04%)  1 1/2515 (0.04%)  1
Clostridium difficile colitis  1  2/2519 (0.08%)  2 0/2515 (0.00%)  0
Complicated appendicitis  1  2/2519 (0.08%)  2 0/2515 (0.00%)  0
Cystitis  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Cystitis bacterial  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Device related infection  1  4/2519 (0.16%)  4 2/2515 (0.08%)  2
Diabetic foot infection  1  1/2519 (0.04%)  1 2/2515 (0.08%)  2
Diarrhoea infectious  1  1/2519 (0.04%)  1 1/2515 (0.04%)  1
Disseminated tuberculosis  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Diverticulitis  1  1/2519 (0.04%)  1 2/2515 (0.08%)  2
Endocarditis  1  4/2519 (0.16%)  7 1/2515 (0.04%)  1
Enteritis infectious  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Enterobacter bacteraemia  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Enterococcal bacteraemia  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Enterococcal infection  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Enterocolitis viral  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Epididymitis  1  2/2519 (0.08%)  2 0/2515 (0.00%)  0
Erysipelas  1  2/2519 (0.08%)  2 6/2515 (0.24%)  6
Escherichia urinary tract infection  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Extradural abscess  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Eye infection bacterial  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Febrile infection  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Fungaemia  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Gangrene  1  4/2519 (0.16%)  4 4/2515 (0.16%)  4
Gas gangrene  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Gastroenteritis  1  16/2519 (0.64%)  16 10/2515 (0.40%)  10
Gastroenteritis bacterial  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Gastroenteritis norovirus  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Gastroenteritis salmonella  1  1/2519 (0.04%)  1 1/2515 (0.04%)  1
Gastroenteritis viral  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Groin abscess  1  0/2519 (0.00%)  0 2/2515 (0.08%)  2
H1N1 influenza  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Haematoma infection  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Herpes zoster  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Implant site cellulitis  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Implant site infection  1  3/2519 (0.12%)  3 3/2515 (0.12%)  3
Infected bite  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Infected skin ulcer  1  2/2519 (0.08%)  2 0/2515 (0.00%)  0
Infection  1  0/2519 (0.00%)  0 3/2515 (0.12%)  3
Infectious pleural effusion  1  1/2519 (0.04%)  1 1/2515 (0.04%)  1
Infective exacerbation of chronic obstructive airways disease  1  1/2519 (0.04%)  1 3/2515 (0.12%)  3
Influenza  1  11/2519 (0.44%)  11 8/2515 (0.32%)  8
Intervertebral discitis  1  1/2519 (0.04%)  1 1/2515 (0.04%)  1
Intestinal sepsis  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Klebsiella sepsis  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Liver abscess  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Localised infection  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Lower respiratory tract infection  1  7/2519 (0.28%)  8 4/2515 (0.16%)  4
Lower respiratory tract infection viral  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Lung infection  1  10/2519 (0.40%)  12 3/2515 (0.12%)  3
Measles  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Medical device site abscess  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Myocarditis infectious  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Necrotising fasciitis  1  2/2519 (0.08%)  2 0/2515 (0.00%)  0
Nosocomial infection  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Ophthalmic herpes zoster  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Osteomyelitis  1  6/2519 (0.24%)  6 6/2515 (0.24%)  7
Osteomyelitis acute  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Osteomyelitis chronic  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Otitis externa  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Parainfluenzae virus infection  1  1/2519 (0.04%)  1 1/2515 (0.04%)  1
Parotid abscess  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Periodontitis  1  1/2519 (0.04%)  1 1/2515 (0.04%)  1
Perirectal abscess  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Peritonitis  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Peritonitis bacterial  1  2/2519 (0.08%)  2 0/2515 (0.00%)  0
Pertussis  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Pneumonia  1  104/2519 (4.13%)  113 116/2515 (4.61%)  127
Pneumonia bacterial  1  3/2519 (0.12%)  3 4/2515 (0.16%)  4
Pneumonia chlamydial  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Pneumonia mycoplasmal  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Pneumonia pneumococcal  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Pneumonia respiratory syncytial viral  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Pneumonia staphylococcal  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Pneumonia streptococcal  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Pneumonia viral  1  1/2519 (0.04%)  1 1/2515 (0.04%)  1
Postoperative wound infection  1  2/2519 (0.08%)  2 1/2515 (0.04%)  1
Pseudomembranous colitis  1  0/2519 (0.00%)  0 2/2515 (0.08%)  2
Psoas abscess  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Pulmonary sepsis  1  2/2519 (0.08%)  2 3/2515 (0.12%)  3
Pyelonephritis  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Pyelonephritis acute  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Pyelonephritis chronic  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Renal abscess  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Respiratory tract infection  1  5/2519 (0.20%)  5 4/2515 (0.16%)  4
Respiratory tract infection viral  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Salmonella bacteraemia  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Sepsis  1  16/2519 (0.64%)  16 25/2515 (0.99%)  25
Septic shock  1  11/2519 (0.44%)  11 14/2515 (0.56%)  14
Serratia bacteraemia  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Sinusitis  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Skin bacterial infection  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Skin infection  1  2/2519 (0.08%)  4 0/2515 (0.00%)  0
Staphylococcal bacteraemia  1  2/2519 (0.08%)  2 2/2515 (0.08%)  2
Staphylococcal infection  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Staphylococcal sepsis  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Staphylococcal skin infection  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Streptococcal bacteraemia  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Subcutaneous abscess  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Systemic candida  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Thrombophlebitis septic  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Tooth abscess  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Tracheobronchitis  1  2/2519 (0.08%)  2 0/2515 (0.00%)  0
Tuberculous pleurisy  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Typhoid fever  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Upper respiratory tract infection  1  11/2519 (0.44%)  11 10/2515 (0.40%)  10
Ureter abscess  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Urinary tract infection  1  20/2519 (0.79%)  23 16/2515 (0.64%)  18
Urosepsis  1  7/2519 (0.28%)  8 0/2515 (0.00%)  0
Vestibular neuronitis  1  1/2519 (0.04%)  1 2/2515 (0.08%)  2
Viral diarrhoea  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Viral infection  1  2/2519 (0.08%)  2 0/2515 (0.00%)  0
Viral upper respiratory tract infection  1  3/2519 (0.12%)  3 0/2515 (0.00%)  0
West Nile viral infection  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Wound infection  1  0/2519 (0.00%)  0 4/2515 (0.16%)  4
Wound sepsis  1  0/2519 (0.00%)  0 2/2515 (0.08%)  2
Injury, poisoning and procedural complications     
Accidental overdose  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Acetabulum fracture  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Alcohol poisoning  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Ankle fracture  1  2/2519 (0.08%)  2 0/2515 (0.00%)  0
Arterial bypass occlusion  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Arteriovenous fistula site complication  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Asbestosis  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Bone fissure  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Burns second degree  1  1/2519 (0.04%)  1 1/2515 (0.04%)  1
Burns third degree  1  0/2519 (0.00%)  0 2/2515 (0.08%)  2
Cardiac valve replacement complication  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Cervical vertebral fracture  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Chest injury  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Concussion  1  3/2519 (0.12%)  3 0/2515 (0.00%)  0
Contusion  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Coronary vascular graft stenosis  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Costal cartilage fracture  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Craniocerebral injury  1  1/2519 (0.04%)  1 2/2515 (0.08%)  2
Facial bones fracture  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Fall  1  6/2519 (0.24%)  6 5/2515 (0.20%)  5
Femoral neck fracture  1  2/2519 (0.08%)  3 8/2515 (0.32%)  8
Femur fracture  1  3/2519 (0.12%)  3 12/2515 (0.48%)  12
Fibula fracture  1  1/2519 (0.04%)  1 1/2515 (0.04%)  1
Foot fracture  1  2/2519 (0.08%)  2 1/2515 (0.04%)  1
Head injury  1  4/2519 (0.16%)  4 1/2515 (0.04%)  1
Heat illness  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Hip fracture  1  6/2519 (0.24%)  6 3/2515 (0.12%)  3
Humerus fracture  1  0/2519 (0.00%)  0 3/2515 (0.12%)  3
Incision site haemorrhage  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Limb crushing injury  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Limb injury  1  1/2519 (0.04%)  1 5/2515 (0.20%)  5
Lower limb fracture  1  1/2519 (0.04%)  1 2/2515 (0.08%)  2
Lumbar vertebral fracture  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Multiple injuries  1  0/2519 (0.00%)  0 2/2515 (0.08%)  2
Overdose  1  1/2519 (0.04%)  1 2/2515 (0.08%)  2
Patella fracture  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Pelvic fracture  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Penis injury  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Post procedural haematuria  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Post procedural haemorrhage  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Post procedural hypothyroidism  1  0/2519 (0.00%)  0 1/2515 (0.04%)  2
Postoperative hypotension  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Pubis fracture  1  2/2519 (0.08%)  2 1/2515 (0.04%)  1
Radius fracture  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Rib fracture  1  1/2519 (0.04%)  1 1/2515 (0.04%)  1
Road traffic accident  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Sedation complication  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Seroma  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Skin laceration  1  3/2519 (0.12%)  3 0/2515 (0.00%)  0
Snake bite  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Spinal compression fracture  1  1/2519 (0.04%)  1 1/2515 (0.04%)  1
Spinal fracture  1  0/2519 (0.00%)  0 2/2515 (0.08%)  2
Subdural haematoma  1  6/2519 (0.24%)  6 1/2515 (0.04%)  1
Subdural haemorrhage  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Suture related complication  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Tendon rupture  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Thermal burn  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Thoracic vertebral fracture  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Tibia fracture  1  1/2519 (0.04%)  1 2/2515 (0.08%)  2
Toxicity to various agents  1  1/2519 (0.04%)  1 6/2515 (0.24%)  6
Traumatic fracture  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Traumatic liver injury  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Traumatic ulcer  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Upper limb fracture  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Urinary retention postoperative  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Vascular graft occlusion  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Vascular pseudoaneurysm  1  1/2519 (0.04%)  1 3/2515 (0.12%)  3
Vasoplegia syndrome  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Wrist fracture  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Investigations     
Alanine aminotransferase increased  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Angiocardiogram  1  1/2519 (0.04%)  1 1/2515 (0.04%)  1
Anticoagulation drug level above therapeutic  1  2/2519 (0.08%)  2 1/2515 (0.04%)  1
Aspartate aminotransferase increased  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Blood bilirubin increased  1  0/2519 (0.00%)  0 2/2515 (0.08%)  2
Blood creatinine increased  1  1/2519 (0.04%)  1 1/2515 (0.04%)  1
Blood potassium increased  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Blood sodium decreased  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Blood urea increased  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Bone density abnormal  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Cardiac index abnormal  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Cardiac stress test abnormal  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Catheterisation cardiac  1  1/2519 (0.04%)  1 1/2515 (0.04%)  1
Cortisol decreased  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Ejection fraction decreased  1  0/2519 (0.00%)  0 3/2515 (0.12%)  3
Gamma-glutamyltransferase increased  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Haemoglobin decreased  1  1/2519 (0.04%)  1 1/2515 (0.04%)  1
Heart rate irregular  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Hepatic enzyme abnormal  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Hepatic enzyme increased  1  2/2519 (0.08%)  2 2/2515 (0.08%)  2
Influenza A virus test positive  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
International normalised ratio increased  1  1/2519 (0.04%)  1 2/2515 (0.08%)  2
Liver function test abnormal  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Liver function test increased  1  1/2519 (0.04%)  1 1/2515 (0.04%)  1
Occult blood positive  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Transaminases increased  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Troponin increased  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Weight decreased  1  1/2519 (0.04%)  1 1/2515 (0.04%)  1
Weight increased  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Metabolism and nutrition disorders     
Cachexia  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Dehydration  1  7/2519 (0.28%)  7 12/2515 (0.48%)  13
Diabetes mellitus  1  5/2519 (0.20%)  6 10/2515 (0.40%)  11
Diabetes mellitus inadequate control  1  0/2519 (0.00%)  0 2/2515 (0.08%)  2
Diabetes with hyperosmolarity  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Diabetic ketoacidosis  1  4/2519 (0.16%)  4 2/2515 (0.08%)  2
Diabetic metabolic decompensation  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Fluid overload  1  2/2519 (0.08%)  2 1/2515 (0.04%)  1
Gout  1  10/2519 (0.40%)  12 12/2515 (0.48%)  14
Hyperammonaemia  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Hypercalcaemia  1  1/2519 (0.04%)  1 1/2515 (0.04%)  1
Hyperglycaemia  1  6/2519 (0.24%)  6 4/2515 (0.16%)  4
Hyperglycaemic hyperosmolar nonketotic syndrome  1  3/2519 (0.12%)  3 2/2515 (0.08%)  2
Hyperkalaemia  1  13/2519 (0.52%)  13 14/2515 (0.56%)  14
Hypernatraemia  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Hyperosmolar state  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Hypoalbuminaemia  1  0/2519 (0.00%)  0 2/2515 (0.08%)  2
Hypocalcaemia  1  2/2519 (0.08%)  2 0/2515 (0.00%)  0
Hypochloraemia  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Hypoglycaemia  1  12/2519 (0.48%)  13 9/2515 (0.36%)  9
Hypokalaemia  1  7/2519 (0.28%)  8 7/2515 (0.28%)  7
Hypomagnesaemia  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Hyponatraemia  1  5/2519 (0.20%)  5 5/2515 (0.20%)  5
Hypophosphataemia  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Hypovolaemia  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Ketoacidosis  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Marasmus  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Metabolic acidosis  1  2/2519 (0.08%)  2 4/2515 (0.16%)  4
Metabolic alkalosis  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Mineral metabolism disorder  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Type 2 diabetes mellitus  1  5/2519 (0.20%)  5 8/2515 (0.32%)  8
Musculoskeletal and connective tissue disorders     
Arthralgia  1  4/2519 (0.16%)  4 1/2515 (0.04%)  1
Arthritis  1  0/2519 (0.00%)  0 2/2515 (0.08%)  2
Back pain  1  6/2519 (0.24%)  6 3/2515 (0.12%)  3
Cervical spinal stenosis  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Chondritis  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Enthesopathy  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Gouty arthritis  1  7/2519 (0.28%)  9 6/2515 (0.24%)  7
Gouty tophus  1  0/2519 (0.00%)  0 2/2515 (0.08%)  2
Haematoma muscle  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Intervertebral disc disorder  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Intervertebral disc protrusion  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Lumbar spinal stenosis  1  1/2519 (0.04%)  2 5/2515 (0.20%)  5
Muscular weakness  1  1/2519 (0.04%)  1 1/2515 (0.04%)  1
Musculoskeletal chest pain  1  1/2519 (0.04%)  1 4/2515 (0.16%)  4
Musculoskeletal pain  1  4/2519 (0.16%)  4 0/2515 (0.00%)  0
Osteoarthritis  1  3/2519 (0.12%)  3 2/2515 (0.08%)  2
Osteonecrosis  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Pain in extremity  1  1/2519 (0.04%)  1 3/2515 (0.12%)  4
Pathological fracture  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Polyarthritis  1  1/2519 (0.04%)  1 1/2515 (0.04%)  1
Rhabdomyolysis  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Rheumatoid arthritis  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Sjogren's syndrome  1  1/2519 (0.04%)  1 1/2515 (0.04%)  1
Spinal pain  1  1/2519 (0.04%)  1 3/2515 (0.12%)  3
Spinal stenosis  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Spondylitis  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Tendonitis  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Adenocarcinoma gastric  1  3/2519 (0.12%)  3 1/2515 (0.04%)  1
Adenocarcinoma of colon  1  2/2519 (0.08%)  2 1/2515 (0.04%)  1
Adenocarcinoma pancreas  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Adrenal gland cancer metastatic  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Angiocentric lymphoma  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Basal cell carcinoma  1  1/2519 (0.04%)  1 2/2515 (0.08%)  2
Benign gastric neoplasm  1  1/2519 (0.04%)  1 1/2515 (0.04%)  1
Benign neoplasm of bladder  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Bladder cancer  1  2/2519 (0.08%)  2 0/2515 (0.00%)  0
Bladder cancer recurrent  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Bladder neoplasm  1  1/2519 (0.04%)  1 1/2515 (0.04%)  1
Bladder transitional cell carcinoma  1  0/2519 (0.00%)  0 2/2515 (0.08%)  2
Bowen's disease  1  0/2519 (0.00%)  0 1/2515 (0.04%)  2
Breast cancer  1  0/2519 (0.00%)  0 4/2515 (0.16%)  4
Bronchial carcinoma  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Chronic lymphocytic leukaemia  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Colon adenoma  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Colon cancer  1  1/2519 (0.04%)  1 1/2515 (0.04%)  1
Colon neoplasm  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Cutaneous T-cell lymphoma  1  1/2519 (0.04%)  2 0/2515 (0.00%)  0
Diffuse large B-cell lymphoma  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Gastric cancer  1  3/2519 (0.12%)  3 1/2515 (0.04%)  1
Glioblastoma multiforme  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Hepatic cancer  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Hepatic cancer metastatic  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Hepatic neoplasm  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Hepatobiliary cancer  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Hepatocellular carcinoma  1  0/2519 (0.00%)  0 2/2515 (0.08%)  2
Inflammatory pseudotumour  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Lung adenocarcinoma  1  1/2519 (0.04%)  1 1/2515 (0.04%)  1
Lung cancer metastatic  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Lung neoplasm malignant  1  0/2519 (0.00%)  0 4/2515 (0.16%)  4
Lymphoma  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Lymphoproliferative disorder  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Malignant melanoma  1  1/2519 (0.04%)  1 1/2515 (0.04%)  1
Meningioma  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Metastases to abdominal cavity  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Metastases to bone  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Metastases to central nervous system  1  1/2519 (0.04%)  1 1/2515 (0.04%)  1
Metastases to lung  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Metastases to lymph nodes  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Metastatic neoplasm  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Myelodysplastic syndrome  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Oesophageal carcinoma  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Oropharyngeal cancer  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Oropharyngeal squamous cell carcinoma  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Ovarian cancer  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Pancreatic carcinoma  1  1/2519 (0.04%)  1 1/2515 (0.04%)  1
Pancreatic carcinoma metastatic  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Plasma cell myeloma  1  1/2519 (0.04%)  1 2/2515 (0.08%)  2
Plasmacytoma  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Polycythaemia vera  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Prostate cancer  1  2/2519 (0.08%)  2 5/2515 (0.20%)  5
Prostate cancer metastatic  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Rectal cancer  1  0/2519 (0.00%)  0 2/2515 (0.08%)  2
Rectosigmoid cancer  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Renal cancer  1  1/2519 (0.04%)  1 1/2515 (0.04%)  1
Renal neoplasm  1  3/2519 (0.12%)  3 0/2515 (0.00%)  0
Retroperitoneal cancer  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Skin cancer  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Squamous cell carcinoma  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Squamous cell carcinoma of head and neck  1  2/2519 (0.08%)  2 0/2515 (0.00%)  0
Squamous cell carcinoma of lung  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Squamous cell carcinoma of the oral cavity  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Sweat gland tumour  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
T-cell lymphoma  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Tongue neoplasm malignant stage unspecified  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Tumour ulceration  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Uterine cancer  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Uterine leiomyoma  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Waldenstrom's macroglobulinaemia  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Nervous system disorders     
Altered state of consciousness  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Autonomic neuropathy  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Axonal neuropathy  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Brain hypoxia  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Brain injury  1  2/2519 (0.08%)  2 1/2515 (0.04%)  1
Brain oedema  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Carotid artery stenosis  1  0/2519 (0.00%)  0 3/2515 (0.12%)  3
Cauda equina syndrome  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Cerebral artery embolism  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Cerebral artery stenosis  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Cerebral haemorrhage  1  1/2519 (0.04%)  1 1/2515 (0.04%)  1
Cerebral infarction  1  1/2519 (0.04%)  1 2/2515 (0.08%)  2
Cerebral ischaemia  1  1/2519 (0.04%)  1 1/2515 (0.04%)  1
Cerebrovascular accident  1  3/2519 (0.12%)  3 6/2515 (0.24%)  6
Cerebrovascular disorder  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Cognitive disorder  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Coma  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Dementia  1  2/2519 (0.08%)  2 0/2515 (0.00%)  0
Dementia Alzheimer's type  1  0/2519 (0.00%)  0 2/2515 (0.08%)  2
Diabetic neuropathy  1  0/2519 (0.00%)  0 2/2515 (0.08%)  2
Dizziness  1  6/2519 (0.24%)  6 2/2515 (0.08%)  2
Dizziness postural  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Dysarthria  1  0/2519 (0.00%)  0 2/2515 (0.08%)  2
Encephalopathy  1  0/2519 (0.00%)  0 2/2515 (0.08%)  2
Facial paralysis  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Generalised tonic-clonic seizure  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Headache  1  1/2519 (0.04%)  1 1/2515 (0.04%)  1
Hemiparesis  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Hepatic encephalopathy  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Hydrocephalus  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Hypoxic-ischaemic encephalopathy  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Ischaemic stroke  1  2/2519 (0.08%)  2 2/2515 (0.08%)  2
Lethargy  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Loss of consciousness  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Lumbar radiculopathy  1  2/2519 (0.08%)  2 0/2515 (0.00%)  0
Metabolic encephalopathy  1  1/2519 (0.04%)  1 2/2515 (0.08%)  2
Myelopathy  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Myoclonus  1  0/2519 (0.00%)  0 2/2515 (0.08%)  2
Neuropathy peripheral  1  2/2519 (0.08%)  2 0/2515 (0.00%)  0
Paraesthesia  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Post stroke epilepsy  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Presyncope  1  4/2519 (0.16%)  4 0/2515 (0.00%)  0
Sciatica  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Seizure  1  2/2519 (0.08%)  2 2/2515 (0.08%)  2
Spinal cord compression  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Status epilepticus  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Subarachnoid haemorrhage  1  1/2519 (0.04%)  1 1/2515 (0.04%)  1
Syncope  1  43/2519 (1.71%)  45 33/2515 (1.31%)  35
Tension headache  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Toxic encephalopathy  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Transient ischaemic attack  1  2/2519 (0.08%)  2 2/2515 (0.08%)  2
Vascular dementia  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Vertebrobasilar insufficiency  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Product Issues     
Device battery issue  1  1/2519 (0.04%)  1 4/2515 (0.16%)  4
Device dislocation  1  0/2519 (0.00%)  0 2/2515 (0.08%)  3
Device failure  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Device ineffective  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Device malfunction  1  1/2519 (0.04%)  1 4/2515 (0.16%)  4
Lead dislodgement  1  1/2519 (0.04%)  2 0/2515 (0.00%)  0
Psychiatric disorders     
Alcohol abuse  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Anxiety  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Anxiety disorder  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Confusional state  1  1/2519 (0.04%)  1 2/2515 (0.08%)  2
Delirium  1  0/2519 (0.00%)  0 3/2515 (0.12%)  4
Depression  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Drug use disorder  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Mental status changes  1  0/2519 (0.00%)  0 2/2515 (0.08%)  2
Panic attack  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Suicide attempt  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Renal and urinary disorders     
Acute kidney injury  1  66/2519 (2.62%)  69 51/2515 (2.03%)  53
Azotaemia  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Bladder cyst  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Bladder mass  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Calculus bladder  1  2/2519 (0.08%)  2 0/2515 (0.00%)  0
Chronic kidney disease  1  40/2519 (1.59%)  42 31/2515 (1.23%)  31
Costovertebral angle tenderness  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
End stage renal disease  1  2/2519 (0.08%)  2 1/2515 (0.04%)  1
Haematuria  1  3/2519 (0.12%)  3 7/2515 (0.28%)  7
Nephritis  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Nephrolithiasis  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Nephropathy  1  3/2519 (0.12%)  3 1/2515 (0.04%)  1
Nephrotic syndrome  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Renal artery stenosis  1  1/2519 (0.04%)  1 1/2515 (0.04%)  1
Renal colic  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Renal cyst  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Renal failure  1  24/2519 (0.95%)  25 30/2515 (1.19%)  31
Renal impairment  1  6/2519 (0.24%)  6 7/2515 (0.28%)  7
Renal infarct  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Renal mass  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Urate nephropathy  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Ureterolithiasis  1  2/2519 (0.08%)  2 0/2515 (0.00%)  0
Urethral stenosis  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Urinary retention  1  2/2519 (0.08%)  2 2/2515 (0.08%)  2
Reproductive system and breast disorders     
Benign prostatic hyperplasia  1  1/2519 (0.04%)  1 8/2515 (0.32%)  8
Endometrial hyperplasia  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Acute pulmonary oedema  1  4/2519 (0.16%)  5 1/2515 (0.04%)  1
Acute respiratory failure  1  9/2519 (0.36%)  9 7/2515 (0.28%)  7
Asthma  1  6/2519 (0.24%)  6 4/2515 (0.16%)  6
Atelectasis  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Bronchial haemorrhage  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Bronchitis chronic  1  2/2519 (0.08%)  2 0/2515 (0.00%)  0
Bronchospasm  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Chronic obstructive pulmonary disease  1  38/2519 (1.51%)  51 30/2515 (1.19%)  50
Chylothorax  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Cough  1  0/2519 (0.00%)  0 2/2515 (0.08%)  2
Dyspnoea  1  11/2519 (0.44%)  11 7/2515 (0.28%)  7
Dyspnoea exertional  1  0/2519 (0.00%)  0 3/2515 (0.12%)  3
Epistaxis  1  1/2519 (0.04%)  1 2/2515 (0.08%)  2
Haemoptysis  1  0/2519 (0.00%)  0 2/2515 (0.08%)  3
Haemothorax  1  0/2519 (0.00%)  0 2/2515 (0.08%)  2
Hyperventilation  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Hypoxia  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Interstitial lung disease  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Obstructive airways disorder  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Pleural effusion  1  6/2519 (0.24%)  8 13/2515 (0.52%)  15
Pleurisy  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Pleuritic pain  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Pneumonia aspiration  1  6/2519 (0.24%)  7 2/2515 (0.08%)  2
Pneumothorax  1  2/2519 (0.08%)  2 4/2515 (0.16%)  4
Pulmonary congestion  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Pulmonary embolism  1  4/2519 (0.16%)  4 6/2515 (0.24%)  6
Pulmonary haematoma  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Pulmonary hypertension  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Pulmonary infarction  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Pulmonary mass  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Pulmonary oedema  1  4/2519 (0.16%)  4 3/2515 (0.12%)  4
Respiratory disorder  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Respiratory failure  1  3/2519 (0.12%)  3 5/2515 (0.20%)  5
Rhinitis hypertrophic  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Sleep apnoea syndrome  1  1/2519 (0.04%)  1 1/2515 (0.04%)  1
Tonsillar haemorrhage  1  1/2519 (0.04%)  2 0/2515 (0.00%)  0
Skin and subcutaneous tissue disorders     
Angioedema  1  1/2519 (0.04%)  1 1/2515 (0.04%)  1
Dermatitis bullous  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Diabetic foot  1  1/2519 (0.04%)  1 4/2515 (0.16%)  4
Drug eruption  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Ecchymosis  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Haemorrhage subcutaneous  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Henoch-Schonlein purpura  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Neurodermatitis  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Psoriasis  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Skin necrosis  1  1/2519 (0.04%)  1 1/2515 (0.04%)  1
Skin ulcer  1  5/2519 (0.20%)  5 9/2515 (0.36%)  14
Stasis dermatitis  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Stevens-Johnson syndrome  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Urticaria  1  1/2519 (0.04%)  1 0/2515 (0.00%)  0
Surgical and medical procedures     
Aortic aneurysm repair  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Arrhythmia prophylaxis  1  0/2519 (0.00%)  0 1/2515 (0.04%)  1
Cardiac pacemaker replacement  1  0/2519 (0.00%)  0