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A Phase III Study of Apixaban in Patients With Atrial Fibrillation (AVERROES)

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ClinicalTrials.gov Identifier: NCT00496769
Recruitment Status : Completed
First Posted : July 4, 2007
Results First Posted : November 14, 2013
Last Update Posted : June 15, 2018
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Bristol-Myers Squibb

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Prevention
Condition Atrial Fibrillation
Interventions Drug: Apixaban
Drug: Acetylsalicylic acid
Enrollment 6421
Recruitment Details  
Pre-assignment Details A total 6421 patients were enrolled in the study. Of these, 5598 were randomized (2807 to apixaban and 2791 to acetylsalicylic acid). Most (435) of the patients who were not randomized (823) no longer met study criteria. Of those randomized, 5578 received treatment (2798 with apixaban, and 2780 with acetylsalicylic acid).
Arm/Group Title Apixaban, 2.5 or 5 mg Twice Daily Acetylsalicylic Acid, 81-324 mg Once Daily Open Label Apixaban
Hide Arm/Group Description Patients received 5 mg of apixaban twice daily. Participants who fulfilled any 2 of the following criteria at baseline received apixaban, 2.5 mg twice daily: age older than 80 years, body weight of 60 kg or less, Serum creatinine level ≥1.5 mg/dL. Participants randomized to the 2.5 mg twice daily dose of apixaban continued on this dose throughout the study even if they no longer fulfilled the previous criteria. Patients received 81 to 324 mg of acetylsalicylic acid once daily, with dosage based on investigator discretion Participants who completed the double-blind treatment period and met eligibility criteria had the option of enrolling in the Long Term Open Label Extension to receive open-label apixaban. Participants who completed the double-blind treatment period and met eligibility criteria had the option of enrolling in the Long Term Open Label Extension to receive open-label apixaban.
Period Title: Double Blind
Started 2807 [1] 2791 [1] 0
Received Treatment 2798 2708 0
Completed 2249 2142 0
Not Completed 558 649 0
Reason Not Completed
>=1 reason assigned per patient             558             649             0
[1]
Randomized
Period Title: Open Label
Started 0 0 3275
Completed 0 0 2264
Not Completed 0 0 1011
Reason Not Completed
>=1 reason assigned per patient             0             0             1011
Arm/Group Title Apixaban, 2.5 or 5 mg Twice Daily Acetylsalicylic Acid, 81-324 mg Once Daily Total
Hide Arm/Group Description Patients received 5 mg of apixaban twice daily. Participants who fulfilled any 2 of the following criteria at baseline received apixaban, 2.5 mg twice daily: age older than 80 years, body weight of 60 kg or less, Serum creatinine level ≥1.5 mg/dL. Participants randomized to the 2.5 mg twice daily dose of apixaban continued on this dose throughout the study even if they no longer fulfilled the previous criteria. Patients received 81 to 324 mg of acetylsalicylic acid once daily, with dosage based on investigator discretion Total of all reporting groups
Overall Number of Baseline Participants 2807 2791 5598
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 2807 participants 2791 participants 5598 participants
69.7  (9.44) 70.0  (9.71) 69.9  (9.58)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2807 participants 2791 participants 5598 participants
< 65 years
855
  30.5%
865
  31.0%
1720
  30.7%
>=65 but <75 years
1049
  37.4%
938
  33.6%
1987
  35.5%
>=75 years
903
  32.2%
988
  35.4%
1891
  33.8%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2807 participants 2791 participants 5598 participants
Female
1147
  40.9%
1174
  42.1%
2321
  41.5%
Male
1660
  59.1%
1617
  57.9%
3277
  58.5%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2807 participants 2791 participants 5598 participants
American Indian or Alaska Native
6
   0.2%
6
   0.2%
12
   0.2%
Asian
541
  19.3%
544
  19.5%
1085
  19.4%
Native Hawaiian or Other Pacific Islander
3
   0.1%
1
   0.0%
4
   0.1%
Black or African American
10
   0.4%
26
   0.9%
36
   0.6%
White
2221
  79.1%
2178
  78.0%
4399
  78.6%
Other
26
   0.9%
36
   1.3%
62
   1.1%
Number of Participants by Number of Risk Factors for Stroke  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2807 participants 2791 participants 5598 participants
1 or fewer
1085
  38.7%
1077
  38.6%
2162
  38.6%
2 or more
1722
  61.3%
1714
  61.4%
3436
  61.4%
Number of Participants With Risk Factors for Stroke   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2807 participants 2791 participants 5598 participants
Age of 75 years or older
903
  32.2%
988
  35.4%
1891
  33.8%
Prior stroke or transient ischemic attack
390
  13.9%
374
  13.4%
764
  13.6%
Heart failure (NYHA class ≥2) or LVEF ≤35%
961
  34.2%
926
  33.2%
1887
  33.7%
Diabetes mellitus
536
  19.1%
559
  20.0%
1095
  19.6%
Hypertension requiring pharmacologic treatment
2408
  85.8%
2429
  87.0%
4837
  86.4%
Peripheral artery disease
66
   2.4%
78
   2.8%
144
   2.6%
[1]
Measure Description: NYHA=New York Health Authority; LVEF=left ventricular ejection fraction
1.Primary Outcome
Title Event Rate of Stroke/Systemic Embolism During the Intended-treatment Period
Hide Description Event rate=percent of participants with an event divided by the total participants in the arm. Intended-treatment period=date of randomization to the efficacy cutoff date, which was to be the date on which at least 226 unrefuted original primary efficacy events occurred (date revised to May 28, 2010 following cessation of study for superior efficacy.)
Time Frame Randomization to efficacy cutoff date of May 28, 2010 (date revised following cessation of study for superior efficacy)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study drug.
Arm/Group Title Apixaban, 2.5 or 5 mg Twice Daily Acetylsalicylic Acid, 81-324 mg Once Daily
Hide Arm/Group Description:
Patients received 5 mg of apixaban twice daily. Participants who fulfilled any 2 of the following criteria at baseline received apixaban, 2.5 mg twice daily: age older than 80 years, body weight of 60 kg or less, Serum creatinine level ≥1.5 mg/dL. Participants randomized to the 2.5 mg twice daily dose of apixaban continued on this dose throughout the study even if they no longer fulfilled the previous criteria.
Patients received 81 to 324 mg of acetylsalicylic acid once daily, with dosage based on investigator discretion
Overall Number of Participants Analyzed 2807 2791
Measure Type: Number
Unit of Measure: Percentage of events
1.62 3.63
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Apixaban, 2.5 or 5 mg Twice Daily, Acetylsalicylic Acid, 81-324 mg Once Daily
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.00001
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.45
Confidence Interval (2-Sided) 95%
0.32 to 0.62
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Event Rate for the Composite of Stroke of Any Type, Systemic Embolism, Myocardial Infarction, or Vascular Death During the Double-blind Treatment Period
Hide Description Event rate=percent of participants with an event divided by the total participants in the arm.
Time Frame Randomization to efficacy cutoff date of May 28, 2010 (date revised following cessation of study for superior efficacy)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study drug.
Arm/Group Title Apixaban, 2.5 or 5 mg Twice Daily Acetylsalicylic Acid, 81-324 mg Once Daily
Hide Arm/Group Description:

Patients received 5 mg of apixaban twice daily. Participants who fulfilled any 2 of the following criteria at baseline received apixaban, 2.5 mg twice daily: age older than 80 years, body weight of 60 kg or less, Serum creatinine level ≥1.5 mg/dL. Participants randomized to the 2.5 mg twice daily dose of apixaban continued on this dose throughout the study even if they no longer fulfilled the previous criteria.

Participants who completed the double-blind treatment period and met eligibility criteria had the option of enrolling in the Long Term Open Label Extension to receive open-label apixaban.

Patients received 81 to 324 mg of acetylsalicylic acid once daily, with dosage based on investigator discretion

Participants who completed the double-blind treatment period and met eligibility criteria had the option of enrolling in the Long Term Open Label Extension to receive open-label apixaban.

Overall Number of Participants Analyzed 2807 2791
Measure Type: Number
Unit of Measure: Percentage of events per year
4.21 6.35
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Apixaban, 2.5 or 5 mg Twice Daily, Acetylsalicylic Acid, 81-324 mg Once Daily
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.00026
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.66
Confidence Interval (2-Sided) 95%
0.53 to 0.83
Estimation Comments Vascular death
3.Secondary Outcome
Title Event Rate of All-cause Death; Net Clinical Benefit-Composite of Stroke, Systemic Embolism, Myocardial Infarction, Vascular Death, and Major Bleeding; and Vascular Death
Hide Description Event rate=percent of participants with an event divided by the total participants in the arm.
Time Frame Randomization to efficacy cutoff date of May 28, 2010 (date revised following cessation of study for superior efficacy)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study drug.
Arm/Group Title Apixaban, 2.5 or 5 mg Twice Daily Acetylsalicylic Acid, 81-324 mg Once Daily
Hide Arm/Group Description:

Patients received 5 mg of apixaban twice daily. Participants who fulfilled any 2 of the following criteria at baseline received apixaban, 2.5 mg twice daily: age older than 80 years, body weight of 60 kg or less, Serum creatinine level ≥1.5 mg/dL. Participants randomized to the 2.5 mg twice daily dose of apixaban continued on this dose throughout the study even if they no longer fulfilled the previous criteria.

Participants who completed the double-blind treatment period and met eligibility criteria had the option of enrolling in the Long Term Open Label Extension to receive open-label apixaban.

Patients received 81 to 324 mg of acetylsalicylic acid once daily, with dosage based on investigator discretion

Participants who completed the double-blind treatment period and met eligibility criteria had the option of enrolling in the Long Term Open Label Extension to receive open-label apixaban.

Overall Number of Participants Analyzed 2807 2791
Measure Type: Number
Unit of Measure: Percentage of events per year
All-cause death (n=111, 140) 3.51 4.42
Net clinical benefit (n=163, 220) 5.23 7.13
Vascular death (n=84, 96) 2.65 3.03
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Apixaban, 2.5 or 5 mg Twice Daily, Acetylsalicylic Acid, 81-324 mg Once Daily
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.06782
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.79
Confidence Interval (2-Sided) 95%
0.62 to 1.02
Estimation Comments All-cause death
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Apixaban, 2.5 or 5 mg Twice Daily, Acetylsalicylic Acid, 81-324 mg Once Daily
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.00280
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.73
Confidence Interval (2-Sided) 95%
0.60 to 0.90
Estimation Comments Composite endpoint of major vascular events and major bleeding-net clinical benefit
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Apixaban, 2.5 or 5 mg Twice Daily, Acetylsalicylic Acid, 81-324 mg Once Daily
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.36586
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.87
Confidence Interval (2-Sided) 95%
0.65 to 1.17
Estimation Comments Vascular death
4.Secondary Outcome
Title Event Rates for Major Bleeding, Major or Clinically Relevant Nonmajor (CNRM) Bleeding, and All Bleeding in the Double-blind Period
Hide Description Event rate=percent of participants with an event divided by the total participants in the arm.
Time Frame First dose of study drug (Day 1) to the earlier of a patient's discontinuation of double-blind study drug or the attainment of at least 226 primary efficacy events up to May 28, 2010
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study drug.
Arm/Group Title Apixaban, 2.5 or 5 mg Twice Daily Acetylsalicylic Acid, 81-324 mg Once Daily
Hide Arm/Group Description:

Patients received 5 mg of apixaban twice daily. Participants who fulfilled any 2 of the following criteria at baseline received apixaban, 2.5 mg twice daily: age older than 80 years, body weight of 60 kg or less, Serum creatinine level ≥1.5 mg/dL. Participants randomized to the 2.5 mg twice daily dose of apixaban continued on this dose throughout the study even if they no longer fulfilled the previous criteria.

Participants who completed the double-blind treatment period and met eligibility criteria had the option of enrolling in the Long Term Open Label Extension to receive open-label apixaban.

Patients received 81 to 324 mg of acetylsalicylic acid once daily, with dosage based on investigator discretion

Participants who completed the double-blind treatment period and met eligibility criteria had the option of enrolling in the Long Term Open Label Extension to receive open-label apixaban.

Overall Number of Participants Analyzed 2798 2780
Measure Type: Number
Unit of Measure: Percentage of events per year
Major bleeding 1.41 0.92
Major or CRNM bleeding 4.46 3.24
All bleeding 10.85 8.32
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Apixaban, 2.5 or 5 mg Twice Daily, Acetylsalicylic Acid, 81-324 mg Once Daily
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0716
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.54
Confidence Interval (2-Sided) 95%
0.96 to 2.45
Estimation Comments Major bleeding
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Apixaban, 2.5 or 5 mg Twice Daily, Acetylsalicylic Acid, 81-324 mg Once Daily
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0017
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.30
Confidence Interval (2-Sided) 95%
1.10 to 1.53
Estimation Comments All bleeding
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Apixaban, 2.5 or 5 mg Twice Daily, Acetylsalicylic Acid, 81-324 mg Once Daily
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0144
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.38
Confidence Interval (2-Sided) 95%
1.07 to 1.78
Estimation Comments Major or CNRM bleeding
5.Secondary Outcome
Title Rate of Unrefuted Bleeding From First Dose of Double-blind Study Drug to First Occurence of Unrefuted Bleeding During the Double-blind Treatment Period
Hide Description Event rate=percent of participants with an event divided by the total participants in the arm.
Time Frame Day 1 to first bleeding event up to efficacy cutoff date of May 28, 2010 (date revised following cessation of study for superior efficacy)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study drug.
Arm/Group Title Apixaban, 2.5 or 5 mg Twice Daily Acetylsalicylic Acid, 81-324 mg Once Daily
Hide Arm/Group Description:

Patients received 5 mg of apixaban twice daily. Participants who fulfilled any 2 of the following criteria at baseline received apixaban, 2.5 mg twice daily: age older than 80 years, body weight of 60 kg or less, Serum creatinine level ≥1.5 mg/dL. Participants randomized to the 2.5 mg twice daily dose of apixaban continued on this dose throughout the study even if they no longer fulfilled the previous criteria.

Participants who completed the double-blind treatment period and met eligibility criteria had the option of enrolling in the Long Term Open Label Extension to receive open-label apixaban.

Patients received 81 to 324 mg of acetylsalicylic acid once daily, with dosage based on investigator discretion

Participants who completed the double-blind treatment period and met eligibility criteria had the option of enrolling in the Long Term Open Label Extension to receive open-label apixaban.

Overall Number of Participants Analyzed 2798 2780
Measure Type: Number
Unit of Measure: Percentage of events per year
10.85 8.32
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Apixaban, 2.5 or 5 mg Twice Daily, Acetylsalicylic Acid, 81-324 mg Once Daily
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0017
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.30
Confidence Interval (2-Sided) 95%
1.10 to 1.53
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs), Bleeding AEs, Discontinuations Due to AEs, and Death as Outcome
Hide Description AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.
Time Frame First dose of study drug (Day 1) to 30 days after last dose of blinded study drug
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study drug.
Arm/Group Title Apixaban, 2.5 or 5 mg Twice Daily Acetylsalicylic Acid, 81-324 mg Once Daily
Hide Arm/Group Description:

Patients received 5 mg of apixaban twice daily. Participants who fulfilled any 2 of the following criteria at baseline received apixaban, 2.5 mg twice daily: age older than 80 years, body weight of 60 kg or less, Serum creatinine level ≥1.5 mg/dL. Participants randomized to the 2.5 mg twice daily dose of apixaban continued on this dose throughout the study even if they no longer fulfilled the previous criteria.

Participants who completed the double-blind treatment period and met eligibility criteria had the option of enrolling in the Long Term Open Label Extension to receive open-label apixaban.

Patients received 81 to 324 mg of acetylsalicylic acid once daily, with dosage based on investigator discretion

Participants who completed the double-blind treatment period and met eligibility criteria had the option of enrolling in the Long Term Open Label Extension to receive open-label apixaban.

Overall Number of Participants Analyzed 2798 2780
Measure Type: Number
Unit of Measure: Participants
AEs 1833 1925
SAEs 657 804
Bleeding AEs 281 259
Discontinuations due to AE 266 362
Deaths 91 115
7.Secondary Outcome
Title Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality
Hide Description BL=baseline, LLN=lower limit of normal, ULN=upper limit of normal. Hemoglobin (g/dL), low: BL>2 or value ≤8; hematocrit(%), low: <0.75*BL; erythrocytes (*10^6 cells/μL), low: <0.75*BL; platelet count (*10^9 cells/L),low: <100*10^9 cells/L; leukocytes (*10^3 cells/μL), low if <0.8*BL and BL<LLN or <LLN and BL >ULN or <0.75*LLN when BL is missing or LLN ≤BL≤ ULN, high if >1.2*BL and BL>ULN or >ULN when BL and BL<LLN or >1.25*ULN when BL is missing or LLN≤BL≤ULN; neutrophils (absolute), low: <1.0*10^3 cells/μL; eosinophils (absolute), high: >0.750*10^3 cells/μL; basophils (absolute), high: >0.4*10^3 cells/μL; monocytes (absolute), high: 2*10^3 cells/μL; lymphocytes (absolute), low if <0.75*10^3 cells/μL, high if >7.50*10^3 cells/μL; ALP (U/L), high: 2*ULN; AST (U/L), high: 3*ULN; AST (U/L), high: 3*ULN; bilirubin, total (mg/dL), high: >2*ULN; bilirubin, direct (mg/dL), high: 1.5*ULN; BUN (mg/dL), high:>2*ULN; creatinine (mg/dL), high: >1.5*ULN.
Time Frame First dose of study drug (Day 1) to 30 days after last dose of blinded study drug
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study drug. n=number evaluable
Arm/Group Title Apixaban, 2.5 or 5 mg Twice Daily Acetylsalicylic Acid, 81-324 mg Once Daily
Hide Arm/Group Description:

Patients received 5 mg of apixaban twice daily. Participants who fulfilled any 2 of the following criteria at baseline received apixaban, 2.5 mg twice daily: age older than 80 years, body weight of 60 kg or less, Serum creatinine level ≥1.5 mg/dL. Participants randomized to the 2.5 mg twice daily dose of apixaban continued on this dose throughout the study even if they no longer fulfilled the previous criteria.

Participants who completed the double-blind treatment period and met eligibility criteria had the option of enrolling in the Long Term Open Label Extension to receive open-label apixaban.

Patients received 81 to 324 mg of acetylsalicylic acid once daily, with dosage based on investigator discretion

Participants who completed the double-blind treatment period and met eligibility criteria had the option of enrolling in the Long Term Open Label Extension to receive open-label apixaban.

Overall Number of Participants Analyzed 2798 2780
Measure Type: Number
Unit of Measure: Participants
Hemoglobin, low (n=1956, 1893) 131 120
Hemoglobin, high (n=1956, 1893) 0 0
Hematocrit, low (n=1728, 1687) 13 9
Hematocrit, high (n=1728, 1687) 0 0
Erythrocytes, low (n=1728, 1687) 12 12
Erythrocytes, high (n=1728, 1687) 0 0
Platelet count, low (n=2148, 2098) 7 10
Platelet count, high (n=2148, 2098) 0 0
Leukocytes, low (n=1738, 1698) 12 14
Leukocytes, high (n=1738, 1698) 14 18
Neutrophils (absolute), low (n=2170, 2138) 2 1
Neutrophils (absolute), high (n=2170, 2138) 0 0
Eosinophils (absolute), low (n=2170, 2138) 0 0
Eosinophils (absolute), high (n=2170, 2138) 48 68
Basophils (absolute), low (n=2170, 2138) 0 0
Basophils (absolute), high (n=2170, 2138) 0 0
Monocytes (absolute), low (n=2170, 2138) 0 0
Monocytes (absolute), high (n=2170, 2138) 0 2
Lymphocytes (absolute), low (n=2170, 2138) 52 62
Lymphocytes (absolute), high (n=2170, 2138) 4 5
Alkaline phosphatase (ALP), low (n=2781, 2758) 0 0
ALP, high (n=2781, 2758) 34 27
Aspartate phosphatase (AST), low (n=2779, 2753) 0 0
AST, high (n=2779, 2753) 28 33
Alanine aminotransferase (ALT), low (n=2779, 2753) 0 0
ALT, high (n=2779, 2753) 23 31
Bilirubin (total), low (n=2781, 2758) 0 0
Bilirubin (total), high (n=2781, 2758) 30 43
Bilirubin (direct), low (n=2773, 2750) 0 0
Bilirubin (direct), high (n=2773, 2750) 241 248
Blood urea nitrogen (BUN), low (n=2201, 2172) 0 0
BUN, high (n=2201, 2172) 42 50
Creatinine, low (n=2209, 2178) 0 0
Creatinine, high (n=2209, 2178) 67 71
8.Secondary Outcome
Title Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued)
Hide Description LLN=lower limit of normal; ULN=upper limit of normal; BL=baseline. Sodium, serum (mEq/L):low if <0.95*BL and BL<LLN or <LLN and BL>ULN or <0.95*LLN when BL missing or LLN ≤BL≤ULN, high if >1.05*BL and BL>ULN or >ULN and BL<LLN or >1.05*ULN when BL missing or LLN≤BL≤ULN; potassium(mEq/L):low if <0.90*BL and BL<LLN or <LLN and BL>ULN or <0.90*LLN if BL missing or LLN≤BL≤ULN, high if >1.10*BL and BL>ULN or>ULN and BL<LLN or >1.10*ULN when BL missing or LLN≤BL≤ULN; chloride(mEq/L):low if <0.90*BL and BL<LLN or <LLN and BL>ULN or <0.90*LLN if BL missing or LLN≤BL ≤ULN, high if >1.10*BL and BL>ULN or >ULN and BL<LLN or >1.10* ULN if BL missing or LLN≤BL≤ULN; calcium(mg/dL):low if <0.75*BL and BL<LLN or <LLN and BL>ULN or <0.80*LLN if BL missing or LLN≤BL≤ULN, high if >1.25*BL and BL>ULN or >ULN if BL<LLN or >1.20*ULN if BL missing or LLN≤BL≤ULN ; bicarbonate(mEq/L):low if <0.75*BL when BL<LLN or <LLN when BL>ULN or <0.75*LLN if BL missing or LLN≤BL≤ULN, high if >1.25*BL when BL>ULN or >ULN
Time Frame First dose of study drug (Day 1) to 30 days after last dose of blinded study drug
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study drug. n=number evaluable
Arm/Group Title Apixaban, 2.5 or 5 mg Twice Daily Acetylsalicylic Acid, 81-324 mg Once Daily
Hide Arm/Group Description:

Patients received 5 mg of apixaban twice daily. Participants who fulfilled any 2 of the following criteria at baseline received apixaban, 2.5 mg twice daily: age older than 80 years, body weight of 60 kg or less, Serum creatinine level ≥1.5 mg/dL. Participants randomized to the 2.5 mg twice daily dose of apixaban continued on this dose throughout the study even if they no longer fulfilled the previous criteria.

Participants who completed the double-blind treatment period and met eligibility criteria had the option of enrolling in the Long Term Open Label Extension to receive open-label apixaban.

Patients received 81 to 324 mg of acetylsalicylic acid once daily, with dosage based on investigator discretion

Participants who completed the double-blind treatment period and met eligibility criteria had the option of enrolling in the Long Term Open Label Extension to receive open-label apixaban.

Overall Number of Participants Analyzed 2798 2780
Measure Type: Number
Unit of Measure: Participants
Sodium (serum), low (n=1768, 1740) 2 6
Sodium (serum), high (n=1768, 1740) 1 2
Potassium (serum), low (n=1763, 1737) 6 8
Potassium (serum), high (n=1763, 1737) 20 28
Chloride (serum), low (n=1768, 1740) 0 3
Chloride (serum), high (n=1768, 1740) 0 1
Calcium (total), low (n=106, 109) 0 0
Calcium (total), high (n=106, 109) 0 0
Bicarbonate, low (n=1664, 1619) 0 0
Bicarbonate, high (n=1664, 1619) 0 0
9.Secondary Outcome
Title Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued)
Hide Description ULN=upper limit of normal; LLN=lower limit of normal; BL=baseline. Creatine kinase (U/L), high:>5*ULN; protein, total(g/L):low if <0.90*BL when BL<LLN or <LLN when B >ULN or <0.90*LLN when BL is missing or LLN≤BL≤ULN, high if >1.10*BL if BL>ULN or >ULN when BL<LLN or >1.10*ULN if BL missing or LLN≤BL≤ULN.Protein,total(g/L): low if <0.90*BL if BL<LLN or <LLN if BL>ULN or <0.90*LLN if BL missing or LLN≤BL≤ULN, high if >1.10*BL if BL>ULN or >ULN if BL<LLN or >1.10*ULN if BL or LLN≤BL≤ULN; glucose, serum fasting (mg/dL): low if <0.8*BL if BL<LLN or <LLN when BL>ULN or <0.8*LLN when BL missing or LLN≤BL≤ULN, high if >2*BL when BL>ULN or >ULN when BL<LLN or >1.5*ULN if BL missing or LLN≤BL≤ULN; uric acid (mg/dL), high: >2*BL and BL>ULN or>1.5*ULN when BL missing or BL≤ULN; glucose, urine, high; protein, urine, high; blood, urine, high; leukocyte esterase, urine, high; RBC count, urine (Hpf), high; WBC count, urine (Hpf), high: ≥2 if BL=missing,=0 or =0.5 or if ≥3 if BL=1, or if ≥4 and BL≥2.
Time Frame First dose of study drug (Day 1) to 30 days after last dose of blinded study drug
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Hide Analysis Population Description
Participants who received at least 1 dose of study drug. n=number evaluable
Arm/Group Title Apixaban, 2.5 or 5 mg Twice Daily Acetylsalicylic Acid, 81-324 mg Once Daily
Hide Arm/Group Description:

Patients received 5 mg of apixaban twice daily. Participants who fulfilled any 2 of the following criteria at baseline received apixaban, 2.5 mg twice daily: age older than 80 years, body weight of 60 kg or less, Serum creatinine level ≥1.5 mg/dL. Participants randomized to the 2.5 mg twice daily dose of apixaban continued on this dose throughout the study even if they no longer fulfilled the previous criteria.

Participants who completed the double-blind treatment period and met eligibility criteria had the option of enrolling in the Long Term Open Label Extension to receive open-label apixaban.

Patients received 81 to 324 mg of acetylsalicylic acid once daily, with dosage based on investigator discretion

Participants who completed the double-blind treatment period and met eligibility criteria had the option of enrolling in the Long Term Open Label Extension to receive open-label apixaban.

Overall Number of Participants Analyzed 2798 2780
Measure Type: Number
Unit of Measure: Participants
Creatine kinase, low (n=2780, 2758) 0 0
Creatine kinase, high (n=2780, 2758) 13 25
Protein (total), low (n=103, 109) 0 0
Protein (total), high (n=103, 109) 0 0
Uric acid, low (n=386, 390) 0 0
Uric acid, high (n=386, 390) 1 0
Glucose (urine), low (n=2, 3) 0 0
Glucose (urine), high (n=2, 3) 0 1
Protein (urine), low (n=3, 5) 0 0
Protein (urine), high (n=3, 5) 1 1
Blood (urine), low (n=3, 5) 0 0
Blood (urine), high (n=3, 5) 1 0
Leukocyte esterase (urine), low (n=3,5) 0 0
Leukocyte esterase (urine), high (n=3,5) 0 0
Red blood cells (RBC) (urine), low (n=2,2) 0 0
RBC (urine), high (n=2,2) 1 0
White blood cells (urine), low (n=2,2) 0 0
WBC (urine), high (n=2,2) 0 0
Time Frame From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Apixaban, 2.5 or 5 mg Twice Daily Acetylsalicylic Acid, 81-324 mg Once Daily Open Label Apixaban
Hide Arm/Group Description Patients received 5 mg of apixaban twice daily. Participants who fulfilled any 2 of the following criteria at baseline received apixaban, 2.5 mg twice daily: age older than 80 years, body weight of 60 kg or less, Serum creatinine level ≥1.5 mg/dL. Participants randomized to the 2.5 mg twice daily dose of apixaban continued on this dose throughout the study even if they no longer fulfilled the previous criteria.

Patients received 81 to 324 mg of acetylsalicylic acid once daily, with dosage based on investigator discretion

Participants who completed the double-blind treatment period and met eligibility criteria had the option of enrolling in the Long Term Open Label Extension to receive open-label apixaban.

Participants who completed the double-blind treatment period and met eligibility criteria had the option of enrolling in the Long Term Open Label Extension to receive open-label apixaban.
All-Cause Mortality
Apixaban, 2.5 or 5 mg Twice Daily Acetylsalicylic Acid, 81-324 mg Once Daily Open Label Apixaban
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   111/2798 (3.97%)   140/2780 (5.04%)   286/3275 (8.73%) 
Show Serious Adverse Events Hide Serious Adverse Events
Apixaban, 2.5 or 5 mg Twice Daily Acetylsalicylic Acid, 81-324 mg Once Daily Open Label Apixaban
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   657/2798 (23.48%)   804/2780 (28.92%)   1228/3275 (37.50%) 
Blood and lymphatic system disorders       
Anaemia  1  12/2798 (0.43%)  11/2780 (0.40%)  23/3275 (0.70%) 
Lymphadenopathy  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Thrombocytopenia  1  1/2798 (0.04%)  1/2780 (0.04%)  1/3275 (0.03%) 
Aplastic anaemia  1  0/2798 (0.00%)  1/2780 (0.04%)  1/3275 (0.03%) 
Coagulopathy  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Haemorrhagic diathesis  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Iron deficiency anaemia  1  1/2798 (0.04%)  0/2780 (0.00%)  3/3275 (0.09%) 
Leukocytosis  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Anaemia megaloblastic  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Haemolytic anaemia  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Leukopenia  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Pancytopenia  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Cardiac disorders       
Acute myocardial infarction  1  11/2798 (0.39%)  19/2780 (0.68%)  25/3275 (0.76%) 
Atrial flutter  1  7/2798 (0.25%)  6/2780 (0.22%)  8/3275 (0.24%) 
Cardiac failure  1  60/2798 (2.14%)  76/2780 (2.73%)  116/3275 (3.54%) 
Cardiogenic shock  1  1/2798 (0.04%)  0/2780 (0.00%)  5/3275 (0.15%) 
Palpitations  1  4/2798 (0.14%)  2/2780 (0.07%)  2/3275 (0.06%) 
Pericardial effusion  1  0/2798 (0.00%)  1/2780 (0.04%)  2/3275 (0.06%) 
Atrioventricular block  1  1/2798 (0.04%)  2/2780 (0.07%)  3/3275 (0.09%) 
Bradycardia  1  5/2798 (0.18%)  4/2780 (0.14%)  11/3275 (0.34%) 
Conduction disorder  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Left ventricular dysfunction  1  0/2798 (0.00%)  1/2780 (0.04%)  3/3275 (0.09%) 
Mitral valve prolapse  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Ventricular failure  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Atrial fibrillation  1  72/2798 (2.57%)  70/2780 (2.52%)  113/3275 (3.45%) 
Cardio-respiratory arrest  1  1/2798 (0.04%)  0/2780 (0.00%)  7/3275 (0.21%) 
Cardiovascular insufficiency  1  0/2798 (0.00%)  1/2780 (0.04%)  1/3275 (0.03%) 
Myocardial ischaemia  1  3/2798 (0.11%)  2/2780 (0.07%)  4/3275 (0.12%) 
Sinoatrial block  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Supraventricular tachycardia  1  3/2798 (0.11%)  5/2780 (0.18%)  1/3275 (0.03%) 
Tachyarrhythmia  1  1/2798 (0.04%)  1/2780 (0.04%)  0/3275 (0.00%) 
Acute coronary syndrome  1  3/2798 (0.11%)  6/2780 (0.22%)  7/3275 (0.21%) 
Arrhythmia supraventricular  1  1/2798 (0.04%)  2/2780 (0.07%)  0/3275 (0.00%) 
Atrial tachycardia  1  1/2798 (0.04%)  0/2780 (0.00%)  2/3275 (0.06%) 
Cardiopulmonary failure  1  2/2798 (0.07%)  3/2780 (0.11%)  4/3275 (0.12%) 
Carditis  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Coronary artery disease  1  4/2798 (0.14%)  6/2780 (0.22%)  16/3275 (0.49%) 
Coronary artery insufficiency  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Intracardiac thrombus  1  3/2798 (0.11%)  3/2780 (0.11%)  0/3275 (0.00%) 
Sick sinus syndrome  1  8/2798 (0.29%)  11/2780 (0.40%)  0/3275 (0.00%) 
Ventricular tachycardia  1  3/2798 (0.11%)  3/2780 (0.11%)  4/3275 (0.12%) 
Angina unstable  1  20/2798 (0.71%)  12/2780 (0.43%)  17/3275 (0.52%) 
Atrioventricular block complete  1  3/2798 (0.11%)  2/2780 (0.07%)  1/3275 (0.03%) 
Cardiac failure congestive  1  39/2798 (1.39%)  28/2780 (1.01%)  53/3275 (1.62%) 
Cardiomyopathy  1  1/2798 (0.04%)  1/2780 (0.04%)  1/3275 (0.03%) 
Ischaemic cardiomyopathy  1  1/2798 (0.04%)  0/2780 (0.00%)  3/3275 (0.09%) 
Tachycardia  1  1/2798 (0.04%)  2/2780 (0.07%)  2/3275 (0.06%) 
Tricuspid valve incompetence  1  1/2798 (0.04%)  0/2780 (0.00%)  1/3275 (0.03%) 
Ventricular arrhythmia  1  1/2798 (0.04%)  0/2780 (0.00%)  4/3275 (0.12%) 
Ventricular fibrillation  1  1/2798 (0.04%)  2/2780 (0.07%)  3/3275 (0.09%) 
Arrhythmia  1  0/2798 (0.00%)  2/2780 (0.07%)  4/3275 (0.12%) 
Nodal arrhythmia  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Sinus arrhythmia  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Sinus bradycardia  1  1/2798 (0.04%)  1/2780 (0.04%)  1/3275 (0.03%) 
Angina pectoris  1  4/2798 (0.14%)  9/2780 (0.32%)  14/3275 (0.43%) 
Bradyarrhythmia  1  2/2798 (0.07%)  1/2780 (0.04%)  3/3275 (0.09%) 
Cardiac arrest  1  3/2798 (0.11%)  7/2780 (0.25%)  10/3275 (0.31%) 
Cardiac failure chronic  1  0/2798 (0.00%)  3/2780 (0.11%)  6/3275 (0.18%) 
Cor pulmonale  1  1/2798 (0.04%)  0/2780 (0.00%)  1/3275 (0.03%) 
Mitral valve incompetence  1  1/2798 (0.04%)  3/2780 (0.11%)  5/3275 (0.15%) 
Myocardial infarction  1  11/2798 (0.39%)  12/2780 (0.43%)  24/3275 (0.73%) 
Aortic valve incompetence  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Cardiac failure acute  1  3/2798 (0.11%)  7/2780 (0.25%)  3/3275 (0.09%) 
Coronary artery occlusion  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Left ventricular failure  1  0/2798 (0.00%)  3/2780 (0.11%)  6/3275 (0.18%) 
Microvascular angina  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Right ventricular failure  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Acute left ventricular failure  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Aortic valve stenosis  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Arteriosclerosis coronary artery  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Cardiac asthma  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Cardiac disorder  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Congestive cardiomyopathy  1  0/2798 (0.00%)  0/2780 (0.00%)  3/3275 (0.09%) 
Defect conduction intraventricular  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Hypertensive heart disease  1  0/2798 (0.00%)  0/2780 (0.00%)  2/3275 (0.06%) 
Mitral valve disease  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Mitral valve stenosis  1  0/2798 (0.00%)  0/2780 (0.00%)  4/3275 (0.12%) 
Nodal rhythm  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Pericarditis  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Pericarditis constrictive  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Prinzmetal angina  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Rheumatic heart disease  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Sinus arrest  1  0/2798 (0.00%)  0/2780 (0.00%)  2/3275 (0.06%) 
Sinus node dysfunction  1  0/2798 (0.00%)  0/2780 (0.00%)  18/3275 (0.55%) 
Ventricular extrasystoles  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Congenital, familial and genetic disorders       
Atrial septal defect  1  0/2798 (0.00%)  2/2780 (0.07%)  0/3275 (0.00%) 
Congenital cystic kidney disease  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Liddle's syndrome  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Ear and labyrinth disorders       
Ear disorder  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Vertigo  1  1/2798 (0.04%)  3/2780 (0.11%)  5/3275 (0.15%) 
Vertigo positional  1  0/2798 (0.00%)  1/2780 (0.04%)  1/3275 (0.03%) 
Ear haemorrhage  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Endocrine disorders       
Hyperparathyroidism  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Hyperthyroidism  1  1/2798 (0.04%)  1/2780 (0.04%)  4/3275 (0.12%) 
Thyroid haemorrhage  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Hypothyroidism  1  1/2798 (0.04%)  0/2780 (0.00%)  1/3275 (0.03%) 
Goitre  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Thyroid mass  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Eye disorders       
Eye haemorrhage  1  2/2798 (0.07%)  0/2780 (0.00%)  0/3275 (0.00%) 
Vitreous haemorrhage  1  2/2798 (0.07%)  0/2780 (0.00%)  0/3275 (0.00%) 
Retinal artery occlusion  1  0/2798 (0.00%)  1/2780 (0.04%)  1/3275 (0.03%) 
Retinal detachment  1  0/2798 (0.00%)  2/2780 (0.07%)  0/3275 (0.00%) 
Amaurosis fugax  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Retinal artery embolism  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Cataract  1  2/2798 (0.07%)  0/2780 (0.00%)  6/3275 (0.18%) 
Eye pain  1  0/2798 (0.00%)  0/2780 (0.00%)  2/3275 (0.06%) 
Eyelid ptosis  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Keratitis  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Tolosa-hunt syndrome  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Gastrointestinal disorders       
Abdominal pain upper  1  1/2798 (0.04%)  1/2780 (0.04%)  0/3275 (0.00%) 
Diverticulum  1  0/2798 (0.00%)  1/2780 (0.04%)  2/3275 (0.06%) 
Gastroduodenitis  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Haematochezia  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Intestinal ischaemia  1  0/2798 (0.00%)  2/2780 (0.07%)  0/3275 (0.00%) 
Pancreatitis chronic  1  1/2798 (0.04%)  1/2780 (0.04%)  0/3275 (0.00%) 
Abdominal hernia  1  0/2798 (0.00%)  1/2780 (0.04%)  2/3275 (0.06%) 
Colitis  1  2/2798 (0.07%)  0/2780 (0.00%)  1/3275 (0.03%) 
Duodenal ulcer  1  1/2798 (0.04%)  1/2780 (0.04%)  3/3275 (0.09%) 
Gastric disorder  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Gastritis  1  5/2798 (0.18%)  6/2780 (0.22%)  3/3275 (0.09%) 
Gastritis erosive  1  1/2798 (0.04%)  2/2780 (0.07%)  2/3275 (0.06%) 
Haematemesis  1  1/2798 (0.04%)  0/2780 (0.00%)  4/3275 (0.12%) 
Intestinal obstruction  1  1/2798 (0.04%)  2/2780 (0.07%)  6/3275 (0.18%) 
Lumbar hernia  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Mouth haemorrhage  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Peptic ulcer  1  1/2798 (0.04%)  2/2780 (0.07%)  1/3275 (0.03%) 
Retroperitoneal haematoma  1  0/2798 (0.00%)  1/2780 (0.04%)  1/3275 (0.03%) 
Colonic polyp  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Dyspepsia  1  0/2798 (0.00%)  1/2780 (0.04%)  1/3275 (0.03%) 
Dysphagia  1  1/2798 (0.04%)  0/2780 (0.00%)  1/3275 (0.03%) 
Gastrooesophageal reflux disease  1  0/2798 (0.00%)  1/2780 (0.04%)  1/3275 (0.03%) 
Gingival bleeding  1  2/2798 (0.07%)  1/2780 (0.04%)  0/3275 (0.00%) 
Mesenteric artery embolism  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Oesophageal achalasia  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Rectal haemorrhage  1  7/2798 (0.25%)  1/2780 (0.04%)  8/3275 (0.24%) 
Reflux oesophagitis  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Subileus  1  2/2798 (0.07%)  0/2780 (0.00%)  0/3275 (0.00%) 
Gastric ulcer haemorrhage  1  1/2798 (0.04%)  0/2780 (0.00%)  2/3275 (0.06%) 
Gastrointestinal haemorrhage  1  2/2798 (0.07%)  9/2780 (0.32%)  20/3275 (0.61%) 
Gastrointestinal hypomotility  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Ileus  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Oesophagitis  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Pancreatitis acute  1  1/2798 (0.04%)  1/2780 (0.04%)  3/3275 (0.09%) 
Proctitis ulcerative  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Duodenal ulcer haemorrhage  1  2/2798 (0.07%)  0/2780 (0.00%)  1/3275 (0.03%) 
Duodenitis  1  1/2798 (0.04%)  1/2780 (0.04%)  0/3275 (0.00%) 
Gastric haemorrhage  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Gastrointestinal disorder  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Intestinal haemorrhage  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Large intestinal obstruction  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Melaena  1  5/2798 (0.18%)  1/2780 (0.04%)  5/3275 (0.15%) 
Oesophageal varices haemorrhage  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Spigelian hernia  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Abdominal adhesions  1  1/2798 (0.04%)  0/2780 (0.00%)  1/3275 (0.03%) 
Constipation  1  1/2798 (0.04%)  2/2780 (0.07%)  6/3275 (0.18%) 
Food poisoning  1  0/2798 (0.00%)  1/2780 (0.04%)  2/3275 (0.06%) 
Gastric ulcer  1  1/2798 (0.04%)  1/2780 (0.04%)  4/3275 (0.12%) 
Gastrointestinal perforation  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Mesenteric artery thrombosis  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Nausea  1  1/2798 (0.04%)  0/2780 (0.00%)  1/3275 (0.03%) 
Abdominal pain  1  4/2798 (0.14%)  3/2780 (0.11%)  6/3275 (0.18%) 
Diarrhoea  1  0/2798 (0.00%)  5/2780 (0.18%)  11/3275 (0.34%) 
Faecaloma  1  1/2798 (0.04%)  0/2780 (0.00%)  2/3275 (0.06%) 
Inguinal hernia  1  3/2798 (0.11%)  6/2780 (0.22%)  12/3275 (0.37%) 
Oesophageal stenosis  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Pancreatitis  1  2/2798 (0.07%)  3/2780 (0.11%)  2/3275 (0.06%) 
Small intestinal obstruction  1  1/2798 (0.04%)  0/2780 (0.00%)  2/3275 (0.06%) 
Abdominal strangulated hernia  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Acute abdomen  1  0/2798 (0.00%)  1/2780 (0.04%)  1/3275 (0.03%) 
Duodenal ulcer perforation  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Gastritis haemorrhagic  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Hiatus hernia  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Splenic artery aneurysm  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Tooth loss  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Vomiting  1  2/2798 (0.07%)  1/2780 (0.04%)  1/3275 (0.03%) 
Abdominal distension  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Abdominal mass  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Abdominal wall haematoma  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Ascites  1  0/2798 (0.00%)  0/2780 (0.00%)  3/3275 (0.09%) 
Barrett's oesophagus  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Chronic gastritis  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Colitis ulcerative  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Diverticulum intestinal  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Haemorrhoidal haemorrhage  1  0/2798 (0.00%)  0/2780 (0.00%)  3/3275 (0.09%) 
Haemorrhoids  1  0/2798 (0.00%)  0/2780 (0.00%)  3/3275 (0.09%) 
Ileus paralytic  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Incarcerated umbilical hernia  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Large intestine perforation  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Large intestine polyp  1  0/2798 (0.00%)  0/2780 (0.00%)  3/3275 (0.09%) 
Lower gastrointestinal haemorrhage  1  0/2798 (0.00%)  0/2780 (0.00%)  2/3275 (0.06%) 
Mallory-weiss syndrome  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Oesophageal dilatation  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Proctitis  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Umbilical hernia  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Upper gastrointestinal haemorrhage  1  0/2798 (0.00%)  0/2780 (0.00%)  14/3275 (0.43%) 
Volvulus  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
General disorders       
Chest pain  1  16/2798 (0.57%)  24/2780 (0.86%)  28/3275 (0.85%) 
Gait disturbance  1  0/2798 (0.00%)  2/2780 (0.07%)  1/3275 (0.03%) 
Malaise  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Pain  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Device pacing issue  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Implant site effusion  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Device lead damage  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Generalised oedema  1  1/2798 (0.04%)  1/2780 (0.04%)  1/3275 (0.03%) 
Hernia pain  1  0/2798 (0.00%)  1/2780 (0.04%)  1/3275 (0.03%) 
Sudden cardiac death  1  3/2798 (0.11%)  1/2780 (0.04%)  6/3275 (0.18%) 
Asthenia  1  4/2798 (0.14%)  1/2780 (0.04%)  9/3275 (0.27%) 
Cardiac death  1  1/2798 (0.04%)  1/2780 (0.04%)  3/3275 (0.09%) 
General physical health deterioration  1  3/2798 (0.11%)  1/2780 (0.04%)  1/3275 (0.03%) 
Medical device complication  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Oedema peripheral  1  2/2798 (0.07%)  1/2780 (0.04%)  7/3275 (0.21%) 
Systemic inflammatory response syndrome  1  1/2798 (0.04%)  1/2780 (0.04%)  1/3275 (0.03%) 
Adverse drug reaction  1  0/2798 (0.00%)  1/2780 (0.04%)  3/3275 (0.09%) 
Chest discomfort  1  1/2798 (0.04%)  0/2780 (0.00%)  2/3275 (0.06%) 
Device malfunction  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Pelvic mass  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Fatigue  1  0/2798 (0.00%)  1/2780 (0.04%)  1/3275 (0.03%) 
Hernia  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Multi-organ failure  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Oedema  1  1/2798 (0.04%)  0/2780 (0.00%)  1/3275 (0.03%) 
Pyrexia  1  3/2798 (0.11%)  3/2780 (0.11%)  7/3275 (0.21%) 
Death  1  14/2798 (0.50%)  9/2780 (0.32%)  38/3275 (1.16%) 
Non-cardiac chest pain  1  3/2798 (0.11%)  5/2780 (0.18%)  2/3275 (0.06%) 
Sudden death  1  9/2798 (0.32%)  12/2780 (0.43%)  32/3275 (0.98%) 
Swelling  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Unassigned  1  4/2798 (0.14%)  6/2780 (0.22%)  7/3275 (0.21%) 
Exercise tolerance decreased  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Incarcerated hernia  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Multiple organ dysfunction syndrome  1  0/2798 (0.00%)  0/2780 (0.00%)  5/3275 (0.15%) 
Peripheral swelling  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Unevaluable event  1  0/2798 (0.00%)  0/2780 (0.00%)  2/3275 (0.06%) 
Hepatobiliary disorders       
Cholecystitis  1  5/2798 (0.18%)  6/2780 (0.22%)  4/3275 (0.12%) 
Bile duct stone  1  1/2798 (0.04%)  3/2780 (0.11%)  3/3275 (0.09%) 
Cholestasis  1  1/2798 (0.04%)  0/2780 (0.00%)  1/3275 (0.03%) 
Hepatitis  1  2/2798 (0.07%)  0/2780 (0.00%)  0/3275 (0.00%) 
Cholecystitis chronic  1  1/2798 (0.04%)  0/2780 (0.00%)  1/3275 (0.03%) 
Hepatic failure  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Jaundice cholestatic  1  0/2798 (0.00%)  1/2780 (0.04%)  1/3275 (0.03%) 
Cholelithiasis  1  3/2798 (0.11%)  2/2780 (0.07%)  7/3275 (0.21%) 
Bile duct stenosis  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Cholangitis  1  2/2798 (0.07%)  0/2780 (0.00%)  3/3275 (0.09%) 
Cholecystitis acute  1  5/2798 (0.18%)  2/2780 (0.07%)  4/3275 (0.12%) 
Hyperbilirubinaemia  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Liver disorder  1  0/2798 (0.00%)  1/2780 (0.04%)  1/3275 (0.03%) 
Acute hepatic failure  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Cholangitis acute  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Hepatic cirrhosis  1  0/2798 (0.00%)  0/2780 (0.00%)  2/3275 (0.06%) 
Hepatic cyst  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Hepatitis fulminant  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Hepatomegaly  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Portal hypertension  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Immune system disorders       
Anaphylactic reaction  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Infections and infestations       
Abdominal wall abscess  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Bronchitis  1  7/2798 (0.25%)  7/2780 (0.25%)  15/3275 (0.46%) 
Chronic sinusitis  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Dengue fever  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Hepatitis C  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Infection  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Infective exacerbation of chronic obstructive airways disease  1  1/2798 (0.04%)  2/2780 (0.07%)  1/3275 (0.03%) 
Lobar pneumonia  1  1/2798 (0.04%)  1/2780 (0.04%)  0/3275 (0.00%) 
Postoperative wound infection  1  1/2798 (0.04%)  2/2780 (0.07%)  2/3275 (0.06%) 
Septic shock  1  4/2798 (0.14%)  2/2780 (0.07%)  12/3275 (0.37%) 
Wound infection  1  2/2798 (0.07%)  0/2780 (0.00%)  1/3275 (0.03%) 
Bronchopneumonia  1  2/2798 (0.07%)  5/2780 (0.18%)  0/3275 (0.00%) 
Helicobacter gastritis  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Hepatic amoebiasis  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Influenza  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Meningitis  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Skin infection  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Tracheitis  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Vestibular neuronitis  1  1/2798 (0.04%)  1/2780 (0.04%)  0/3275 (0.00%) 
Abscess  1  0/2798 (0.00%)  1/2780 (0.04%)  1/3275 (0.03%) 
Abscess limb  1  0/2798 (0.00%)  1/2780 (0.04%)  2/3275 (0.06%) 
Amoebic dysentery  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Lung infection  1  0/2798 (0.00%)  1/2780 (0.04%)  2/3275 (0.06%) 
Psoas abscess  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Staphylococcal sepsis  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Viral infection  1  1/2798 (0.04%)  3/2780 (0.11%)  0/3275 (0.00%) 
Arthritis bacterial  1  2/2798 (0.07%)  0/2780 (0.00%)  0/3275 (0.00%) 
Endocarditis  1  1/2798 (0.04%)  1/2780 (0.04%)  3/3275 (0.09%) 
Escherichia bacteraemia  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Gastroenteritis  1  8/2798 (0.29%)  5/2780 (0.18%)  14/3275 (0.43%) 
Klebsiella bacteraemia  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Lower respiratory tract infection  1  2/2798 (0.07%)  2/2780 (0.07%)  5/3275 (0.15%) 
Osteomyelitis  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Pneumonia  1  37/2798 (1.32%)  55/2780 (1.98%)  99/3275 (3.02%) 
Pneumonia klebsiella  1  1/2798 (0.04%)  0/2780 (0.00%)  1/3275 (0.03%) 
Pneumonia pneumococcal  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Pyelonephritis  1  1/2798 (0.04%)  0/2780 (0.00%)  2/3275 (0.06%) 
Pyometra  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Cellulitis  1  6/2798 (0.21%)  5/2780 (0.18%)  13/3275 (0.40%) 
Clostridium colitis  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Diverticulitis  1  0/2798 (0.00%)  3/2780 (0.11%)  7/3275 (0.21%) 
Gangrene  1  0/2798 (0.00%)  1/2780 (0.04%)  1/3275 (0.03%) 
Localised infection  1  0/2798 (0.00%)  1/2780 (0.04%)  2/3275 (0.06%) 
Pneumonia viral  1  0/2798 (0.00%)  2/2780 (0.07%)  0/3275 (0.00%) 
Respiratory tract infection  1  3/2798 (0.11%)  5/2780 (0.18%)  6/3275 (0.18%) 
Sepsis  1  4/2798 (0.14%)  4/2780 (0.14%)  17/3275 (0.52%) 
Sinusitis  1  0/2798 (0.00%)  1/2780 (0.04%)  1/3275 (0.03%) 
Urinary tract infection  1  11/2798 (0.39%)  15/2780 (0.54%)  24/3275 (0.73%) 
Bronchiectasis  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Clostridium difficile colitis  1  0/2798 (0.00%)  2/2780 (0.07%)  1/3275 (0.03%) 
Gastroenteritis salmonella  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Herpes zoster  1  0/2798 (0.00%)  2/2780 (0.07%)  3/3275 (0.09%) 
Pyelonephritis acute  1  1/2798 (0.04%)  2/2780 (0.07%)  1/3275 (0.03%) 
Upper respiratory tract infection  1  3/2798 (0.11%)  1/2780 (0.04%)  3/3275 (0.09%) 
Urosepsis  1  1/2798 (0.04%)  1/2780 (0.04%)  4/3275 (0.12%) 
Appendicitis  1  0/2798 (0.00%)  1/2780 (0.04%)  6/3275 (0.18%) 
Helicobacter infection  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Oral candidiasis  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Urinary tract infection bacterial  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Abdominal wall infection  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Colonic abscess  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Cystitis  1  0/2798 (0.00%)  0/2780 (0.00%)  2/3275 (0.06%) 
Diabetic foot infection  1  0/2798 (0.00%)  0/2780 (0.00%)  2/3275 (0.06%) 
Disseminated tuberculosis  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Diverticulitis intestinal haemorrhagic  1  0/2798 (0.00%)  0/2780 (0.00%)  2/3275 (0.06%) 
Empyema  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Encephalitis viral  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Endophthalmitis  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Erysipelas  1  0/2798 (0.00%)  0/2780 (0.00%)  8/3275 (0.24%) 
Escherichia infection  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Gastroenteritis viral  1  0/2798 (0.00%)  0/2780 (0.00%)  3/3275 (0.09%) 
Gastrointestinal infection  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Groin infection  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Hepatitis E  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Infectious pleural effusion  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Listeriosis  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Liver abscess  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Nasopharyngitis  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Nosocomial infection  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Oesophageal candidiasis  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Ophthalmic herpes zoster  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Orchitis  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Periorbital cellulitis  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Peritonitis  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Pneumonia escherichia  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Pneumonia influenzal  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Prostate infection  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Pulmonary tuberculosis  1  0/2798 (0.00%)  0/2780 (0.00%)  2/3275 (0.06%) 
Sepsis syndrome  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Staphylococcal infection  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Tracheobronchitis  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Tuberculosis  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Tuberculous pleurisy  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Viral upper respiratory tract infection  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Injury, poisoning and procedural complications       
Concussion  1  1/2798 (0.04%)  1/2780 (0.04%)  0/3275 (0.00%) 
Hand fracture  1  2/2798 (0.07%)  0/2780 (0.00%)  0/3275 (0.00%) 
Multiple fractures  1  2/2798 (0.07%)  0/2780 (0.00%)  2/3275 (0.06%) 
Skull fracture  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Traumatic brain injury  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Upper limb fracture  1  0/2798 (0.00%)  1/2780 (0.04%)  4/3275 (0.12%) 
Cerebral haemorrhage traumatic  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Drug toxicity  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Foot fracture  1  0/2798 (0.00%)  1/2780 (0.04%)  1/3275 (0.03%) 
Joint dislocation  1  1/2798 (0.04%)  0/2780 (0.00%)  1/3275 (0.03%) 
Limb traumatic amputation  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Lumbar vertebral fracture  1  1/2798 (0.04%)  2/2780 (0.07%)  7/3275 (0.21%) 
Muscle strain  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Ulna fracture  1  0/2798 (0.00%)  2/2780 (0.07%)  0/3275 (0.00%) 
Fall  1  4/2798 (0.14%)  6/2780 (0.22%)  12/3275 (0.37%) 
Jaw fracture  1  1/2798 (0.04%)  0/2780 (0.00%)  1/3275 (0.03%) 
Muscle rupture  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Post procedural diarrhoea  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Procedural pain  1  0/2798 (0.00%)  1/2780 (0.04%)  1/3275 (0.03%) 
Road traffic accident  1  1/2798 (0.04%)  2/2780 (0.07%)  1/3275 (0.03%) 
Head injury  1  0/2798 (0.00%)  1/2780 (0.04%)  2/3275 (0.06%) 
Lower limb fracture  1  1/2798 (0.04%)  1/2780 (0.04%)  1/3275 (0.03%) 
Meniscus lesion  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Pubis fracture  1  2/2798 (0.07%)  1/2780 (0.04%)  2/3275 (0.06%) 
Spinal column injury  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Therapeutic agent toxicity  1  2/2798 (0.07%)  1/2780 (0.04%)  0/3275 (0.00%) 
Femur fracture  1  5/2798 (0.18%)  6/2780 (0.22%)  11/3275 (0.34%) 
Patella fracture  1  1/2798 (0.04%)  1/2780 (0.04%)  0/3275 (0.00%) 
Post procedural fistula  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Rib fracture  1  1/2798 (0.04%)  1/2780 (0.04%)  2/3275 (0.06%) 
Incisional hernia  1  1/2798 (0.04%)  0/2780 (0.00%)  3/3275 (0.09%) 
Traumatic haematoma  1  0/2798 (0.00%)  2/2780 (0.07%)  0/3275 (0.00%) 
Wound secretion  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Animal bite  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Ankle fracture  1  1/2798 (0.04%)  1/2780 (0.04%)  3/3275 (0.09%) 
Cervical vertebral fracture  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Femoral neck fracture  1  2/2798 (0.07%)  0/2780 (0.00%)  8/3275 (0.24%) 
Humerus fracture  1  1/2798 (0.04%)  1/2780 (0.04%)  0/3275 (0.00%) 
In-stent arterial restenosis  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
In-stent coronary artery restenosis  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Radius fracture  1  0/2798 (0.00%)  1/2780 (0.04%)  1/3275 (0.03%) 
Spinal compression fracture  1  0/2798 (0.00%)  1/2780 (0.04%)  2/3275 (0.06%) 
Contusion  1  2/2798 (0.07%)  1/2780 (0.04%)  0/3275 (0.00%) 
Facial bones fracture  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Hip fracture  1  5/2798 (0.18%)  4/2780 (0.14%)  12/3275 (0.37%) 
Injury  1  1/2798 (0.04%)  0/2780 (0.00%)  1/3275 (0.03%) 
Multiple injuries  1  1/2798 (0.04%)  0/2780 (0.00%)  2/3275 (0.06%) 
Overdose  1  3/2798 (0.11%)  5/2780 (0.18%)  3/3275 (0.09%) 
Subdural haematoma  1  4/2798 (0.14%)  2/2780 (0.07%)  5/3275 (0.15%) 
Thoracic vertebral fracture  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Abdominal wound dehiscence  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Accidental overdose  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Aortic injury  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Brain contusion  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Chest injury  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Confusion postoperative  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Craniocerebral injury  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Fibula fracture  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Fractured sacrum  1  0/2798 (0.00%)  0/2780 (0.00%)  2/3275 (0.06%) 
Incarcerated incisional hernia  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Laceration  1  0/2798 (0.00%)  0/2780 (0.00%)  3/3275 (0.09%) 
Ligament sprain  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Meniscus injury  1  0/2798 (0.00%)  0/2780 (0.00%)  2/3275 (0.06%) 
Pelvic fracture  1  0/2798 (0.00%)  0/2780 (0.00%)  2/3275 (0.06%) 
Periorbital haematoma  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Post procedural haematoma  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Post procedural haematuria  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Post procedural haemorrhage  1  0/2798 (0.00%)  0/2780 (0.00%)  2/3275 (0.06%) 
Procedural haemorrhage  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Scapula fracture  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Spinal fracture  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Stomal hernia  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Subarachnoid haemorrhage  1  0/2798 (0.00%)  0/2780 (0.00%)  2/3275 (0.06%) 
Tendon rupture  1  0/2798 (0.00%)  0/2780 (0.00%)  2/3275 (0.06%) 
Tibia fracture  1  0/2798 (0.00%)  0/2780 (0.00%)  3/3275 (0.09%) 
Toxicity to various agents  1  0/2798 (0.00%)  0/2780 (0.00%)  5/3275 (0.15%) 
Traumatic haemorrhage  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Wound evisceration  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Wrist fracture  1  0/2798 (0.00%)  0/2780 (0.00%)  2/3275 (0.06%) 
Investigations       
Blood magnesium decreased  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Cystoscopy  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Ejection fraction decreased  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Hepatic enzyme increased  1  1/2798 (0.04%)  1/2780 (0.04%)  0/3275 (0.00%) 
Angiogram  1  1/2798 (0.04%)  3/2780 (0.11%)  1/3275 (0.03%) 
Arteriogram coronary  1  1/2798 (0.04%)  1/2780 (0.04%)  1/3275 (0.03%) 
Heart rate irregular  1  1/2798 (0.04%)  0/2780 (0.00%)  1/3275 (0.03%) 
Red blood cell sedimentation rate increased  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Liver function test abnormal  1  1/2798 (0.04%)  2/2780 (0.07%)  0/3275 (0.00%) 
Prostatic specific antigen increased  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Weight decreased  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Arthroscopy  1  0/2798 (0.00%)  0/2780 (0.00%)  2/3275 (0.06%) 
Blood creatinine increased  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Ecg signs of myocardial ischaemia  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Haemoglobin decreased  1  0/2798 (0.00%)  0/2780 (0.00%)  2/3275 (0.06%) 
Heart rate abnormal  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Liver function test increased  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Platelet count decreased  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Metabolism and nutrition disorders       
Hypoglycaemia  1  8/2798 (0.29%)  3/2780 (0.11%)  12/3275 (0.37%) 
Diabetes mellitus inadequate control  1  0/2798 (0.00%)  2/2780 (0.07%)  3/3275 (0.09%) 
Gout  1  2/2798 (0.07%)  2/2780 (0.07%)  1/3275 (0.03%) 
Hyperkalaemia  1  0/2798 (0.00%)  2/2780 (0.07%)  5/3275 (0.15%) 
Malnutrition  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Decreased appetite  1  1/2798 (0.04%)  1/2780 (0.04%)  2/3275 (0.06%) 
Starvation  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Type 2 diabetes mellitus  1  1/2798 (0.04%)  1/2780 (0.04%)  2/3275 (0.06%) 
Cachexia  1  0/2798 (0.00%)  2/2780 (0.07%)  0/3275 (0.00%) 
Dehydration  1  7/2798 (0.25%)  5/2780 (0.18%)  11/3275 (0.34%) 
Hypokalaemia  1  0/2798 (0.00%)  3/2780 (0.11%)  2/3275 (0.06%) 
Hyponatraemia  1  4/2798 (0.14%)  3/2780 (0.11%)  6/3275 (0.18%) 
Obesity  1  0/2798 (0.00%)  1/2780 (0.04%)  1/3275 (0.03%) 
Electrolyte imbalance  1  1/2798 (0.04%)  0/2780 (0.00%)  2/3275 (0.06%) 
Hyperglycaemia  1  3/2798 (0.11%)  1/2780 (0.04%)  2/3275 (0.06%) 
Hypovolaemia  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Diabetes mellitus  1  5/2798 (0.18%)  4/2780 (0.14%)  6/3275 (0.18%) 
Diabetes with hyperosmolarity  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Hypernatraemia  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Hypomagnesaemia  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Hypophosphataemia  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Lactic acidosis  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Metabolic acidosis  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Musculoskeletal and connective tissue disorders       
Lumbar spinal stenosis  1  0/2798 (0.00%)  1/2780 (0.04%)  4/3275 (0.12%) 
Musculoskeletal stiffness  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Osteochondrosis  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Spinal column stenosis  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Myopathy  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Rotator cuff syndrome  1  0/2798 (0.00%)  2/2780 (0.07%)  1/3275 (0.03%) 
Spinal osteoarthritis  1  1/2798 (0.04%)  0/2780 (0.00%)  4/3275 (0.12%) 
Joint swelling  1  1/2798 (0.04%)  0/2780 (0.00%)  1/3275 (0.03%) 
Musculoskeletal chest pain  1  1/2798 (0.04%)  0/2780 (0.00%)  3/3275 (0.09%) 
Osteoarthritis  1  11/2798 (0.39%)  3/2780 (0.11%)  17/3275 (0.52%) 
Polyarthritis  1  0/2798 (0.00%)  1/2780 (0.04%)  1/3275 (0.03%) 
Intervertebral disc protrusion  1  0/2798 (0.00%)  4/2780 (0.14%)  4/3275 (0.12%) 
Muscle spasms  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Pain in extremity  1  1/2798 (0.04%)  1/2780 (0.04%)  0/3275 (0.00%) 
Systemic lupus erythematosus  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Back pain  1  5/2798 (0.18%)  3/2780 (0.11%)  9/3275 (0.27%) 
Gouty arthritis  1  1/2798 (0.04%)  2/2780 (0.07%)  2/3275 (0.06%) 
Haemarthrosis  1  1/2798 (0.04%)  0/2780 (0.00%)  1/3275 (0.03%) 
Muscle haemorrhage  1  1/2798 (0.04%)  0/2780 (0.00%)  1/3275 (0.03%) 
Osteopenia  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Arthralgia  1  1/2798 (0.04%)  2/2780 (0.07%)  2/3275 (0.06%) 
Musculoskeletal pain  1  0/2798 (0.00%)  1/2780 (0.04%)  1/3275 (0.03%) 
Arthritis  1  0/2798 (0.00%)  0/2780 (0.00%)  2/3275 (0.06%) 
Bursitis  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Inguinal mass  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Intervertebral disc degeneration  1  0/2798 (0.00%)  0/2780 (0.00%)  2/3275 (0.06%) 
Muscular weakness  1  0/2798 (0.00%)  0/2780 (0.00%)  2/3275 (0.06%) 
Myalgia  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Plantar fasciitis  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Polymyalgia rheumatica  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Rhabdomyolysis  1  0/2798 (0.00%)  0/2780 (0.00%)  2/3275 (0.06%) 
Rheumatoid arthritis  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Spinal pain  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Tendon pain  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Breast cancer  1  9/2798 (0.32%)  1/2780 (0.04%)  10/3275 (0.31%) 
Cholesteatoma  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Colon cancer metastatic  1  1/2798 (0.04%)  1/2780 (0.04%)  0/3275 (0.00%) 
Gastric cancer  1  1/2798 (0.04%)  2/2780 (0.07%)  2/3275 (0.06%) 
Laryngeal cancer  1  0/2798 (0.00%)  2/2780 (0.07%)  0/3275 (0.00%) 
Lip and/or oral cavity cancer  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Lung neoplasm malignant  1  3/2798 (0.11%)  5/2780 (0.18%)  15/3275 (0.46%) 
Neoplasm prostate  1  1/2798 (0.04%)  0/2780 (0.00%)  1/3275 (0.03%) 
Non-Hodgkin's lymphoma stage III  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Pancreatic carcinoma  1  0/2798 (0.00%)  1/2780 (0.04%)  6/3275 (0.18%) 
Prostatic adenoma  1  2/2798 (0.07%)  0/2780 (0.00%)  3/3275 (0.09%) 
Uterine leiomyoma  1  0/2798 (0.00%)  2/2780 (0.07%)  2/3275 (0.06%) 
Bladder cancer  1  1/2798 (0.04%)  0/2780 (0.00%)  4/3275 (0.12%) 
Brain neoplasm benign  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Omentum neoplasm  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Renal cell carcinoma  1  1/2798 (0.04%)  0/2780 (0.00%)  2/3275 (0.06%) 
Breast cancer metastatic  1  0/2798 (0.00%)  1/2780 (0.04%)  1/3275 (0.03%) 
Bronchial carcinoma  1  0/2798 (0.00%)  2/2780 (0.07%)  0/3275 (0.00%) 
Leukaemia  1  2/2798 (0.07%)  0/2780 (0.00%)  1/3275 (0.03%) 
Metastases to abdominal cavity  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Biliary neoplasm  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Hepatic neoplasm malignant  1  1/2798 (0.04%)  1/2780 (0.04%)  0/3275 (0.00%) 
Malignant melanoma  1  1/2798 (0.04%)  2/2780 (0.07%)  2/3275 (0.06%) 
Lipoma  1  1/2798 (0.04%)  0/2780 (0.00%)  1/3275 (0.03%) 
Lung adenocarcinoma metastatic  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Lung cancer metastatic  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Lymph node cancer metastatic  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Metastases to central nervous system  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Neoplasm malignant  1  1/2798 (0.04%)  1/2780 (0.04%)  1/3275 (0.03%) 
Rectal cancer metastatic  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Sebaceous carcinoma  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Squamous cell carcinoma  1  2/2798 (0.07%)  4/2780 (0.14%)  7/3275 (0.21%) 
Cervix carcinoma stage 0  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Gastrointestinal carcinoma  1  1/2798 (0.04%)  0/2780 (0.00%)  1/3275 (0.03%) 
Leiomyoma  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Malignant melanoma stage I  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Pelvic neoplasm  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Renal cancer stage III  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Squamous cell carcinoma of skin  1  2/2798 (0.07%)  0/2780 (0.00%)  4/3275 (0.12%) 
Basal cell carcinoma  1  5/2798 (0.18%)  5/2780 (0.18%)  12/3275 (0.37%) 
Basosquamous carcinoma  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Colon cancer  1  2/2798 (0.07%)  1/2780 (0.04%)  5/3275 (0.15%) 
Liposarcoma  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Prostate cancer recurrent  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Renal neoplasm  1  1/2798 (0.04%)  1/2780 (0.04%)  0/3275 (0.00%) 
Colon neoplasm  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Endometrial cancer  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Gallbladder cancer  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Lymphoma  1  1/2798 (0.04%)  0/2780 (0.00%)  2/3275 (0.06%) 
Metastases to liver  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Prostate cancer  1  7/2798 (0.25%)  10/2780 (0.36%)  12/3275 (0.37%) 
Rectal cancer  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Renal cancer  1  0/2798 (0.00%)  1/2780 (0.04%)  1/3275 (0.03%) 
Squamous cell carcinoma of the cervix  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Acute myeloid leukaemia  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Adenocarcinoma gastric  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Adenocarcinoma of colon  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Adrenal adenoma  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
B-cell lymphoma  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
B-cell small lymphocytic lymphoma stage iv  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Bladder cancer stage 0, with cancer in situ  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Bladder neoplasm  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Bowen's disease  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Brain cancer metastatic  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Brain neoplasm  1  0/2798 (0.00%)  0/2780 (0.00%)  4/3275 (0.12%) 
Carcinoid tumour of the caecum  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Cholangiocarcinoma  1  0/2798 (0.00%)  0/2780 (0.00%)  2/3275 (0.06%) 
Chronic lymphocytic leukaemia  1  0/2798 (0.00%)  0/2780 (0.00%)  2/3275 (0.06%) 
Colorectal cancer  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Diffuse large b-cell lymphoma  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Gastrointestinal stromal tumour  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Hepatocellular carcinoma  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Intraductal papillary mucinous neoplasm  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Intraocular melanoma  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Invasive ductal breast carcinoma  1  0/2798 (0.00%)  0/2780 (0.00%)  2/3275 (0.06%) 
Leiomyosarcoma metastatic  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Light chain disease  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Lung adenocarcinoma  1  0/2798 (0.00%)  0/2780 (0.00%)  2/3275 (0.06%) 
Lung neoplasm  1  0/2798 (0.00%)  0/2780 (0.00%)  2/3275 (0.06%) 
Meningioma  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Metastases to bone  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Metastases to pleura  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Metastatic neoplasm  1  0/2798 (0.00%)  0/2780 (0.00%)  2/3275 (0.06%) 
Metastatic renal cell carcinoma  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Myeloproliferative neoplasm  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Neoplasm  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Neuroendocrine tumour  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Non-hodgkin's lymphoma  1  1/2798 (0.04%)  0/2780 (0.00%)  2/3275 (0.06%) 
Oesophageal adenocarcinoma  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Oesophageal cancer metastatic  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Ovarian cancer  1  0/2798 (0.00%)  0/2780 (0.00%)  3/3275 (0.09%) 
Paraneoplastic syndrome  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Plasma cell myeloma  1  0/2798 (0.00%)  0/2780 (0.00%)  2/3275 (0.06%) 
Prostate cancer metastatic  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Rectal adenocarcinoma  1  0/2798 (0.00%)  0/2780 (0.00%)  2/3275 (0.06%) 
Seborrhoeic keratosis  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Skin cancer  1  0/2798 (0.00%)  0/2780 (0.00%)  3/3275 (0.09%) 
Throat cancer  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Thyroid adenoma  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Transitional cell carcinoma  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Tumour haemorrhage  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Uterine cancer  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Vocal cord neoplasm  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Nervous system disorders       
Cerebral infarction  1  1/2798 (0.04%)  6/2780 (0.22%)  10/3275 (0.31%) 
Dementia  1  0/2798 (0.00%)  1/2780 (0.04%)  1/3275 (0.03%) 
Dizziness  1  1/2798 (0.04%)  10/2780 (0.36%)  6/3275 (0.18%) 
Haemorrhagic cerebral infarction  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Lethargy  1  0/2798 (0.00%)  1/2780 (0.04%)  1/3275 (0.03%) 
Loss of consciousness  1  0/2798 (0.00%)  1/2780 (0.04%)  2/3275 (0.06%) 
Metabolic encephalopathy  1  0/2798 (0.00%)  2/2780 (0.07%)  1/3275 (0.03%) 
Peripheral nerve palsy  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Tremor  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Vertebrobasilar insufficiency  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Migraine  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Parkinson's disease  1  0/2798 (0.00%)  4/2780 (0.14%)  4/3275 (0.12%) 
Subarachnoid haemorrhage  1  0/2798 (0.00%)  2/2780 (0.07%)  0/3275 (0.00%) 
Cerebral haemorrhage  1  3/2798 (0.11%)  1/2780 (0.04%)  10/3275 (0.31%) 
Cubital tunnel syndrome  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Depressed level of consciousness  1  0/2798 (0.00%)  1/2780 (0.04%)  1/3275 (0.03%) 
Embolic stroke  1  0/2798 (0.00%)  2/2780 (0.07%)  3/3275 (0.09%) 
Hemiparesis  1  1/2798 (0.04%)  1/2780 (0.04%)  0/3275 (0.00%) 
Partial seizures  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Presyncope  1  5/2798 (0.18%)  2/2780 (0.07%)  4/3275 (0.12%) 
Sciatica  1  0/2798 (0.00%)  1/2780 (0.04%)  1/3275 (0.03%) 
VIIth nerve paralysis  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Cerebral microhaemorrhage  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Cerebral thrombosis  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Cervical root pain  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Encephalopathy  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Epilepsy  1  2/2798 (0.07%)  1/2780 (0.04%)  3/3275 (0.09%) 
Lumbar radiculopathy  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Neuropathy peripheral  1  1/2798 (0.04%)  1/2780 (0.04%)  0/3275 (0.00%) 
Paraesthesia  1  1/2798 (0.04%)  1/2780 (0.04%)  0/3275 (0.00%) 
Cerebral haematoma  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Convulsion  1  1/2798 (0.04%)  2/2780 (0.07%)  0/3275 (0.00%) 
Headache  1  1/2798 (0.04%)  1/2780 (0.04%)  2/3275 (0.06%) 
Ischaemic stroke  1  19/2798 (0.68%)  46/2780 (1.65%)  22/3275 (0.67%) 
Lacunar infarction  1  0/2798 (0.00%)  1/2780 (0.04%)  1/3275 (0.03%) 
Transient ischaemic attack  1  10/2798 (0.36%)  29/2780 (1.04%)  13/3275 (0.40%) 
Vascular encephalopathy  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Diabetic hyperglycaemic coma  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Haemorrhagic stroke  1  5/2798 (0.18%)  6/2780 (0.22%)  8/3275 (0.24%) 
Aphasia  1  0/2798 (0.00%)  1/2780 (0.04%)  1/3275 (0.03%) 
Brain stem infarction  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Carotid arterial embolus  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Cerebral cyst  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Cerebrovascular disorder  1  0/2798 (0.00%)  1/2780 (0.04%)  2/3275 (0.06%) 
Ischaemic cerebral infarction  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Syncope  1  8/2798 (0.29%)  18/2780 (0.65%)  26/3275 (0.79%) 
Altered state of consciousness  1  0/2798 (0.00%)  1/2780 (0.04%)  2/3275 (0.06%) 
Brain stem haemorrhage  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Cerebellar ataxia  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Cerebrovascular accident  1  16/2798 (0.57%)  40/2780 (1.44%)  15/3275 (0.46%) 
Cerebrovascular insufficiency  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Cognitive disorder  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Dementia alzheimer's type  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Diabetic neuropathy  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Dysarthria  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Dyskinesia  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Haemorrhage intracranial  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Hydrocephalus  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Hypoaesthesia  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Hypoglycaemic coma  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Hyponatraemic encephalopathy  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Intraventricular haemorrhage  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Myoclonus  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Neuritis  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Neuroglycopenia  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Paraplegia  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Seizure  1  0/2798 (0.00%)  0/2780 (0.00%)  3/3275 (0.09%) 
Simple partial seizures  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Status epilepticus  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Subdural effusion  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Thrombotic stroke  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Uraemic encephalopathy  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Vascular dementia  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Autonomic nervous system imbalance  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Balance disorder  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Basal ganglia haemorrhage  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Carotid artery stenosis  1  0/2798 (0.00%)  0/2780 (0.00%)  4/3275 (0.12%) 
Carpal tunnel syndrome  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Cerebellar infarction  1  0/2798 (0.00%)  0/2780 (0.00%)  2/3275 (0.06%) 
Cerebral artery embolism  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Pregnancy, puerperium and perinatal conditions       
Cephalhaematoma  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Product Issues       
Lead dislodgement  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Psychiatric disorders       
Alcohol abuse  1  0/2798 (0.00%)  2/2780 (0.07%)  0/3275 (0.00%) 
Anxiety  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Panic attack  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Confusional state  1  3/2798 (0.11%)  0/2780 (0.00%)  2/3275 (0.06%) 
Bipolar disorder  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Delirium  1  0/2798 (0.00%)  3/2780 (0.11%)  0/3275 (0.00%) 
Psychotic disorder  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Alcohol withdrawal syndrome  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Depression  1  2/2798 (0.07%)  1/2780 (0.04%)  3/3275 (0.09%) 
Adjustment disorder  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Bipolar i disorder  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Completed suicide  1  0/2798 (0.00%)  0/2780 (0.00%)  2/3275 (0.06%) 
Hallucination  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Insomnia  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Mental disorder  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Stress  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Suicidal ideation  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Suicide attempt  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Renal and urinary disorders       
Calculus ureteric  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Hypertensive nephropathy  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Renal failure acute  1  8/2798 (0.29%)  9/2780 (0.32%)  0/3275 (0.00%) 
Urinary incontinence  1  2/2798 (0.07%)  0/2780 (0.00%)  0/3275 (0.00%) 
Dysuria  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Renal failure  1  1/2798 (0.04%)  6/2780 (0.22%)  6/3275 (0.18%) 
Urinary retention  1  3/2798 (0.11%)  2/2780 (0.07%)  2/3275 (0.06%) 
Renal impairment  1  0/2798 (0.00%)  1/2780 (0.04%)  2/3275 (0.06%) 
Renal infarct  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Bladder mass  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Haematuria  1  5/2798 (0.18%)  4/2780 (0.14%)  13/3275 (0.40%) 
Renal failure chronic  1  1/2798 (0.04%)  1/2780 (0.04%)  0/3275 (0.00%) 
Urethral disorder  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Renal colic  1  1/2798 (0.04%)  0/2780 (0.00%)  1/3275 (0.03%) 
Calculus urinary  1  3/2798 (0.11%)  0/2780 (0.00%)  1/3275 (0.03%) 
Acute kidney injury  1  0/2798 (0.00%)  0/2780 (0.00%)  24/3275 (0.73%) 
Azotaemia  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Calculus bladder  1  0/2798 (0.00%)  0/2780 (0.00%)  2/3275 (0.06%) 
Calculus urethral  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Chronic kidney disease  1  0/2798 (0.00%)  0/2780 (0.00%)  3/3275 (0.09%) 
Cystitis haemorrhagic  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Diabetic nephropathy  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Haemorrhage urinary tract  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Nephrolithiasis  1  0/2798 (0.00%)  0/2780 (0.00%)  2/3275 (0.06%) 
Postrenal failure  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Renal haemorrhage  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Renal tubular necrosis  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Reproductive system and breast disorders       
Prostatic obstruction  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Menometrorrhagia  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Benign prostatic hyperplasia  1  2/2798 (0.07%)  3/2780 (0.11%)  8/3275 (0.24%) 
Vaginal haemorrhage  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Breast mass  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Metrorrhagia  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Postmenopausal haemorrhage  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Prostatic hypoplasia  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Prostatomegaly  1  0/2798 (0.00%)  0/2780 (0.00%)  2/3275 (0.06%) 
Spermatic cord disorder  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Uterine polyp  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Respiratory, thoracic and mediastinal disorders       
Emphysema  1  0/2798 (0.00%)  1/2780 (0.04%)  1/3275 (0.03%) 
Epistaxis  1  5/2798 (0.18%)  6/2780 (0.22%)  16/3275 (0.49%) 
Lung infiltration  1  1/2798 (0.04%)  0/2780 (0.00%)  1/3275 (0.03%) 
Mediastinal mass  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Haemothorax  1  0/2798 (0.00%)  1/2780 (0.04%)  2/3275 (0.06%) 
Pulmonary fibrosis  1  0/2798 (0.00%)  1/2780 (0.04%)  1/3275 (0.03%) 
Respiratory arrest  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Sleep apnoea syndrome  1  1/2798 (0.04%)  0/2780 (0.00%)  2/3275 (0.06%) 
Allergic bronchitis  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Chronic obstructive pulmonary disease  1  12/2798 (0.43%)  9/2780 (0.32%)  24/3275 (0.73%) 
Dyspnoea  1  13/2798 (0.46%)  11/2780 (0.40%)  22/3275 (0.67%) 
Haemoptysis  1  3/2798 (0.11%)  2/2780 (0.07%)  6/3275 (0.18%) 
Pulmonary artery thrombosis  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Respiratory failure  1  4/2798 (0.14%)  9/2780 (0.32%)  5/3275 (0.15%) 
Dyspnoea exertional  1  0/2798 (0.00%)  1/2780 (0.04%)  4/3275 (0.12%) 
Hiccups  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Lung disorder  1  1/2798 (0.04%)  2/2780 (0.07%)  3/3275 (0.09%) 
Orthopnoea  1  1/2798 (0.04%)  0/2780 (0.00%)  2/3275 (0.06%) 
Pulmonary embolism  1  2/2798 (0.07%)  11/2780 (0.40%)  7/3275 (0.21%) 
Pulmonary oedema  1  2/2798 (0.07%)  2/2780 (0.07%)  3/3275 (0.09%) 
Sinus polyp  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Acute pulmonary oedema  1  4/2798 (0.14%)  2/2780 (0.07%)  4/3275 (0.12%) 
Acute respiratory distress syndrome  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Cough  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Pleural effusion  1  1/2798 (0.04%)  4/2780 (0.14%)  5/3275 (0.15%) 
Acute respiratory failure  1  4/2798 (0.14%)  0/2780 (0.00%)  4/3275 (0.12%) 
Asthma  1  6/2798 (0.21%)  3/2780 (0.11%)  5/3275 (0.15%) 
Bronchitis chronic  1  1/2798 (0.04%)  0/2780 (0.00%)  1/3275 (0.03%) 
Bronchospasm  1  1/2798 (0.04%)  0/2780 (0.00%)  1/3275 (0.03%) 
Pneumonia aspiration  1  3/2798 (0.11%)  2/2780 (0.07%)  3/3275 (0.09%) 
Pneumothorax  1  2/2798 (0.07%)  2/2780 (0.07%)  0/3275 (0.00%) 
Pulmonary hypertension  1  1/2798 (0.04%)  0/2780 (0.00%)  1/3275 (0.03%) 
Respiratory distress  1  0/2798 (0.00%)  3/2780 (0.11%)  3/3275 (0.09%) 
Asphyxia  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Hyperventilation  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Hypoxia  1  0/2798 (0.00%)  0/2780 (0.00%)  2/3275 (0.06%) 
Lung consolidation  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Pleurisy  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Pulmonary congestion  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Pulmonary vascular disorder  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Skin and subcutaneous tissue disorders       
Blood blister  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Skin lesion  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Decubitus ulcer  1  2/2798 (0.07%)  0/2780 (0.00%)  1/3275 (0.03%) 
Dermatitis herpetiformis  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Purpura  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Rash erythematous  1  0/2798 (0.00%)  1/2780 (0.04%)  1/3275 (0.03%) 
Angioedema  1  1/2798 (0.04%)  1/2780 (0.04%)  2/3275 (0.06%) 
Dermatitis  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Diabetic foot  1  0/2798 (0.00%)  0/2780 (0.00%)  3/3275 (0.09%) 
Erythema  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Skin ulcer  1  0/2798 (0.00%)  0/2780 (0.00%)  3/3275 (0.09%) 
Social circumstances       
Activities of daily living impaired  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Physical assault  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Cardiac assistance device user  1  0/2798 (0.00%)  0/2780 (0.00%)  1/3275 (0.03%) 
Surgical and medical procedures       
Cataract operation  1  0/2798 (0.00%)  1/2780 (0.04%)  2/3275 (0.06%) 
Fasciotomy  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Gallbladder operation  1  0/2798 (0.00%)  1/2780 (0.04%)  1/3275 (0.03%) 
Genitourinary operation  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Haemorrhoid operation  1  1/2798 (0.04%)  1/2780 (0.04%)  1/3275 (0.03%) 
Knee arthroplasty  1  1/2798 (0.04%)  1/2780 (0.04%)  6/3275 (0.18%) 
Papilloma excision  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Skin graft  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Abdominoplasty  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%) 
Cardiac pacemaker removal  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Cardiac pacemaker replacement  1  1/2798 (0.04%)  1/2780 (0.04%)  2/3275 (0.06%) 
Cholecystectomy  1  1/2798 (0.04%)  1/2780 (0.04%)  0/3275 (0.00%) 
Implantable defibrillator insertion  1  0/2798 (0.00%)  1/2780 (0.04%)  1/3275 (0.03%) 
Prostatic operation  1  1/2798 (0.04%)  1/2780 (0.04%)  0/3275 (0.00%) 
Tarsal tunnel decompression  1  1/2798 (0.04%)  0/2780 (0.00%)  0/3275 (0.00%) 
Coronary artery bypass  1  0/2798 (0.00%)  1/2780 (0.04%)  1/3275 (0.03%) 
Hysterectomy  1  0/2798 (0.00%)  1/2780 (0.04%)  0/3275 (0.00%)