A Study of AMR101 to Evaluate Its Ability to Reduce Cardiovascular Events in High-Risk Patients With Hypertriglyceridemia and on Statin (REDUCE-IT)

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ClinicalTrials.gov Identifier: NCT01492361

Recruitment Status : Completed

First Posted : December 15, 2011

Results First Posted : April 14, 2022

Last Update Posted : April 14, 2022

View this study on Beta.ClinicalTrials.gov

Sponsor:

Information provided by (Responsible Party):

Amarin Pharma Inc.

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Prevention
Condition	Cardiovascular Diseases
Interventions	Drug: AMR101 Drug: Placebo Drug: Statin therapy
Enrollment	8179

Participant Flow

Recruitment Details
Pre-assignment Details


Arm/Group Title	AMR101	Placebo
Arm/Group Description	AMR101: Parallel Assignment	Placebo: Parallel Assignment
Arm/Group Description	AMR101: Parallel Assignment	Placebo: Parallel Assignment
Period Title: Overall Study
Started	4089	4090
Completed Final Visit	3419	3335
Death Before Final Visit ^[1]	265	295
Completed	3684	3630
Not Completed	405	460
Reason Not Completed
Withdrawal by Subject	281	297
Physician Decision	12	12
Lost to Follow-up	6	13
Other than specified above	106	138
[1] Participants who died on trial were considered completed

Baseline Characteristics

Arm/Group Title		AMR101	Placebo	Total
Arm/Group Description		AMR101: Parallel Assignment	Placebo: Parallel Assignment	Total of all reporting groups
Arm/Group Description		AMR101: Parallel Assignment	Placebo: Parallel Assignment	Total of all reporting groups
Overall Number of Baseline Participants		4089	4090	8179
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Continuous Median (Inter-Quartile Range) Unit of measure: Years
	Number Analyzed	4089 participants	4090 participants	8179 participants
		64.0 (57.0 to 69.0)	64.0 (57.0 to 69.0)	64.0 (57.0 to 69.0)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	4089 participants	4090 participants	8179 participants
	Female	1162 28.4%	1195 29.2%	2357 28.8%
	Male	2927 71.6%	2895 70.8%	5822 71.2%
Race/Ethnicity, Customized Measure Type: Count of Participants Unit of measure: Participants
Race	Number Analyzed	4089 participants	4090 participants	8179 participants
	White	3691 90.3%	3688 90.2%	7379 90.2%
	Other than white	398 9.7%	401 9.8%	799 9.8%
	Missing	0 0.0%	1 0.0%	1 0.0%
Region of Enrollment Measure Type: Number Unit of measure: Participants	Number Analyzed	4089 participants	4090 participants	8179 participants
New Zealand		73	61	134
Canada		123	127	250
Netherlands		847	831	1678
Romania		109	93	202
United States		1548	1598	3146
Ukraine		397	439	836
Poland		195	164	359
South Africa		213	201	414
Australia		102	87	189
India		130	132	262
Russia		352	357	709
Cardiovascular Risk Stratum Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	4089 participants	4090 participants	8179 participants
	Secondary-prevention cohort	2892 70.7%	2893 70.7%	5785 70.7%
	Primary-prevention cohort	1197 29.3%	1197 29.3%	2394 29.3%

Outcome Measures

1.Primary Outcome


Title	Composite of CV Death, Nonfatal MI (Including Silent MI), Nonfatal Stroke, Coronary Revascularization, or Unstable Angina Determined to be Caused by Myocardial Ischemia by Invasive / Non-invasive Testing and Requiring Emergent Hospitalization.
Description	The primary outcome measure was the number of patients with a first oc...
Description	The primary outcome measure was the number of patients with a first occurrence of any component of the composite of CV death, nonfatal MI (including silent MI), nonfatal stroke, coronary revascularization, or unstable angina determined to be caused by myocardial ischemia by invasive / non-invasive testing and requiring emergent hospitalization during the follow-up period.
Time Frame	Total follow-up time of up to approximately 6 years.

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	AMR101	Placebo
Arm/Group Description:	AMR101: Parallel Assignment	Placebo: Parallel Assignment
Arm/Group Description:	AMR101: Parallel Assignment	Placebo: Parallel Assignment
Overall Number of Participants Analyzed	4089	4090
Measure Type: Count of Participants Unit of Measure: Participants
	705 17.2%	901 22.0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AMR101, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.00000001
	Comments	The 2-sided alpha level for the primary analysis was adjusted to 0.0437 from 0.05 to account for the two interim analyses based on a group sequential design with O'Brien-Fleming boundaries generated using the Lan-DeMets alpha-spending function.
	Method	Log Rank
	Comments	Stratified by CV risk category, use of ezetimibe, and geographical region

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.75
	Confidence Interval	(2-Sided) 95% 0.68 to 0.83
	Estimation Comments	[Not Specified]

2.Secondary Outcome


Title	Composite of CV Death, Nonfatal MI (Including Silent MI), or Nonfatal Stroke.
Description	The key secondary outcome measure was the number of patients with a fi...
Description	The key secondary outcome measure was the number of patients with a first occurrence of any component of the composite of CV death, nonfatal MI (including silent MI), or nonfatal stroke during the follow-up period.
Time Frame	Total follow-up time of up to approximately 6 years.

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	AMR101	Placebo
Arm/Group Description:	AMR101: Parallel Assignment	Placebo: Parallel Assignment
Arm/Group Description:	AMR101: Parallel Assignment	Placebo: Parallel Assignment
Overall Number of Participants Analyzed	4089	4090
Measure Type: Count of Participants Unit of Measure: Participants
	459 11.2%	606 14.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AMR101, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.0000006
	Comments	Prespecified secondary end points were tested in a hierarchical fashion, in the order listed here, at the final alpha level of 0.0437.
	Method	Log Rank
	Comments	Stratified by CV risk category, use of ezetimibe, and geographical region.

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.74
	Confidence Interval	(2-Sided) 95% 0.65 to 0.83
	Estimation Comments	[Not Specified]

3.Secondary Outcome


Title	Composite of CV Death or Nonfatal MI (Including Silent MI).
Description	Number of patients with a first occurrence of any component of the com...
Description	Number of patients with a first occurrence of any component of the composite of CV death or nonfatal MI (including silent MI) during the follow-up period.
Time Frame	Total follow-up time of up to approximately 6 years.

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	AMR101	Placebo
Arm/Group Description:	AMR101: Parallel Assignment	Placebo: Parallel Assignment
Arm/Group Description:	AMR101: Parallel Assignment	Placebo: Parallel Assignment
Overall Number of Participants Analyzed	4089	4090
Measure Type: Count of Participants Unit of Measure: Participants
	392 9.6%	507 12.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AMR101, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Prespecified secondary end points were tested in a hierarchical fashion, in the order listed here, at the final alpha level of 0.0437.
	Method	Log Rank
	Comments	Stratified by CV risk category, use of ezetimibe, and geographical region.

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.75
	Confidence Interval	(2-Sided) 95% 0.66 to 0.86
	Estimation Comments	[Not Specified]

4.Secondary Outcome


Title	Fatal or Nonfatal MI (Including Silent MI).
Description	Number of patients with a first occurrence of fatal or nonfatal MI (in...
Description	Number of patients with a first occurrence of fatal or nonfatal MI (including silent MI) during the follow-up period.
Time Frame	Total follow-up time of up to approximately 6 years.

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	AMR101	Placebo
Arm/Group Description:	AMR101: Parallel Assignment	Placebo: Parallel Assignment
Arm/Group Description:	AMR101: Parallel Assignment	Placebo: Parallel Assignment
Overall Number of Participants Analyzed	4089	4090
Measure Type: Count of Participants Unit of Measure: Participants
	250 6.1%	355 8.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AMR101, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Prespecified secondary end points were tested in a hierarchical fashion, in the order listed here, at the final alpha level of 0.0437.
	Method	Log Rank
	Comments	Stratified by CV risk category, use of ezetimibe, and geographical region.

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.69
	Confidence Interval	(2-Sided) 95% 0.58 to 0.81
	Estimation Comments	[Not Specified]

5.Secondary Outcome


Title	Non-elective Coronary Revascularization Represented as the Composite of Emergent or Urgent Classifications.
Description	Number of patients with a first occurrence of non-elective coronary re...
Description	Number of patients with a first occurrence of non-elective coronary revascularization represented as the composite of emergent or urgent classifications during the follow-up period.
Time Frame	Total follow-up time of up to approximately 6 years.

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	AMR101	Placebo
Arm/Group Description:	AMR101: Parallel Assignment	Placebo: Parallel Assignment
Arm/Group Description:	AMR101: Parallel Assignment	Placebo: Parallel Assignment
Overall Number of Participants Analyzed	4089	4090
Measure Type: Count of Participants Unit of Measure: Participants
	216 5.3%	321 7.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AMR101, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Prespecified secondary end points were tested in a hierarchical fashion, in the order listed here, at the final alpha level of 0.0437.
	Method	Log Rank
	Comments	Stratified by CV risk category, use of ezetimibe, and geographical region.

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.65
	Confidence Interval	(2-Sided) 95% 0.55 to 0.78
	Estimation Comments	[Not Specified]

6.Secondary Outcome


Title	CV Death.
Description	Number of patients with an occurrence of CV death during the follow-up...
Description	Number of patients with an occurrence of CV death during the follow-up period.
Time Frame	Total follow-up time of up to approximately 6 years.

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	AMR101	Placebo
Arm/Group Description:	AMR101: Parallel Assignment	Placebo: Parallel Assignment
Arm/Group Description:	AMR101: Parallel Assignment	Placebo: Parallel Assignment
Overall Number of Participants Analyzed	4089	4090
Measure Type: Count of Participants Unit of Measure: Participants
	174 4.3%	213 5.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AMR101, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.0315
	Comments	Prespecified secondary end points were tested in a hierarchical fashion, in the order listed here, at the final alpha level of 0.0437.
	Method	Log Rank
	Comments	Stratified by CV risk category, use of ezetimibe, and geographical region.

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.80
	Confidence Interval	(2-Sided) 95% 0.66 to 0.98
	Estimation Comments	[Not Specified]

7.Secondary Outcome


Title	Unstable Angina Determined to be Caused by Myocardial Ischemia by Invasive / Non-invasive Testing and Requiring Emergent Hospitalization.
Description	Number of patients with a first occurrence of unstable angina determin...
Description	Number of patients with a first occurrence of unstable angina determined to be caused by myocardial ischemia by invasive / non-invasive testing and requiring emergent hospitalization during the follow-up period.
Time Frame	Total follow-up time of up to approximately 6 years.

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	AMR101	Placebo
Arm/Group Description:	AMR101: Parallel Assignment	Placebo: Parallel Assignment
Arm/Group Description:	AMR101: Parallel Assignment	Placebo: Parallel Assignment
Overall Number of Participants Analyzed	4089	4090
Measure Type: Count of Participants Unit of Measure: Participants
	108 2.6%	157 3.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AMR101, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.0018
	Comments	Prespecified secondary end points were tested in a hierarchical fashion, in the order listed here, at the final alpha level of 0.0437.
	Method	Log Rank
	Comments	Stratified by CV risk category, use of ezetimibe, and geographical region.

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.68
	Confidence Interval	(2-Sided) 95% 0.53 to 0.87
	Estimation Comments	[Not Specified]

8.Secondary Outcome


Title	Fatal or Nonfatal Stroke.
Description	Number of patients with a first occurrence of fatal or nonfatal stroke...
Description	Number of patients with a first occurrence of fatal or nonfatal stroke during the follow-up period.
Time Frame	Total follow-up time of up to approximately 6 years.

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	AMR101	Placebo
Arm/Group Description:	AMR101: Parallel Assignment	Placebo: Parallel Assignment
Arm/Group Description:	AMR101: Parallel Assignment	Placebo: Parallel Assignment
Overall Number of Participants Analyzed	4089	4090
Measure Type: Count of Participants Unit of Measure: Participants
	98 2.4%	134 3.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AMR101, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.0129
	Comments	Prespecified secondary end points were tested in a hierarchical fashion, in the order listed here, at the final alpha level of 0.0437.
	Method	Log Rank
	Comments	Stratified by CV risk category, use of ezetimibe, and geographical region.

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.72
	Confidence Interval	(2-Sided) 95% 0.55 to 0.93
	Estimation Comments	[Not Specified]

9.Secondary Outcome


Title	Total Mortality, Nonfatal MI (Including Silent MI), or Nonfatal Stroke.
Description	Number of patients with a first occurrence of any component of the com...
Description	Number of patients with a first occurrence of any component of the composite of total mortality, nonfatal MI (including silent MI), or nonfatal stroke during the follow-up period.
Time Frame	Total follow-up time of up to approximately 6 years.

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	AMR101	Placebo
Arm/Group Description:	AMR101: Parallel Assignment	Placebo: Parallel Assignment
Arm/Group Description:	AMR101: Parallel Assignment	Placebo: Parallel Assignment
Overall Number of Participants Analyzed	4089	4090
Measure Type: Count of Participants Unit of Measure: Participants
	549 13.4%	690 16.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AMR101, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Prespecified secondary end points were tested in a hierarchical fashion, in the order listed here, at the final alpha level of 0.0437.
	Method	Log Rank
	Comments	Stratified by CV risk category, use of ezetimibe, and geographical region.

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.77
	Confidence Interval	(2-Sided) 95% 0.69 to 0.86
	Estimation Comments	[Not Specified]

10.Secondary Outcome


Title	Total Mortality.
Description	Number of patients with an occurrence of death from any cause during t...
Description	Number of patients with an occurrence of death from any cause during the follow-up period.
Time Frame	Total follow-up time of up to approximately 6 years.

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	AMR101	Placebo
Arm/Group Description:	AMR101: Parallel Assignment	Placebo: Parallel Assignment
Arm/Group Description:	AMR101: Parallel Assignment	Placebo: Parallel Assignment
Overall Number of Participants Analyzed	4089	4090
Measure Type: Count of Participants Unit of Measure: Participants
	274 6.7%	310 7.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AMR101, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.0915
	Comments	Prespecified secondary end points were tested in a hierarchical fashion, in the order listed here, at the final alpha level of 0.0437.
	Method	Log Rank
	Comments	Stratified by CV risk category, use of ezetimibe, and geographical region.

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.87
	Confidence Interval	(2-Sided) 95% 0.74 to 1.02
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	Up to maximum duration of approximate 6 years from first dose of study treatment until end of study treatment plus 30 days post treatment.
Adverse Event Reporting Description	Adverse events were collected from first dose of study treatment until the completion or withdrawal from study plus 30 days post treatment.

Arm/Group Title	AMR101	Placebo
Arm/Group Description	AMR101: Parallel Assignment	Placebo: Parallel Assignment
Arm/Group Description	AMR101: Parallel Assignment	Placebo: Parallel Assignment
All-Cause Mortality
	AMR101	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	274/4089 (6.70%)	310/4090 (7.58%)
Serious Adverse Events Serious Adverse Events
	AMR101	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	1252/4089 (30.62%)	1254/4090 (30.66%)
Blood and lymphatic system disorders
Anaemia ^† 1	22/4089 (0.54%)	20/4090 (0.49%)
Iron deficiency anaemia ^† 1	4/4089 (0.10%)	3/4090 (0.07%)
Haemorrhagic anaemia ^† 1	4/4089 (0.10%)	1/4090 (0.02%)
Thrombocytopenia ^† 1	3/4089 (0.07%)	0/4090 (0.00%)
Febrile neutropenia ^† 1	2/4089 (0.05%)	0/4090 (0.00%)
Lymphadenopathy ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Coagulopathy ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Lymphoid tissue hyperplasia ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Neutropenia ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Normocytic anaemia ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Thrombotic microangiopathy ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Autoimmune haemolytic anaemia ^† 1	0/4089 (0.00%)	2/4090 (0.05%)
Pancytopenia ^† 1	0/4089 (0.00%)	2/4090 (0.05%)
Splenic infarction ^† 1	0/4089 (0.00%)	2/4090 (0.05%)
Immune thrombocytopenic purpura ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Microcytic anaemia ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Pernicious anaemia ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Splenomegaly ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Cardiac disorders
Angina pectoris ^† 1	48/4089 (1.17%)	48/4090 (1.17%)
Angina unstable ^† 1	41/4089 (1.00%)	53/4090 (1.30%)
Atrial fibrillation ^† 1	21/4089 (0.51%)	17/4090 (0.42%)
Cardiac failure congestive ^† 1	19/4089 (0.46%)	13/4090 (0.32%)
Aortic valve stenosis ^† 1	10/4089 (0.24%)	7/4090 (0.17%)
Coronary artery disease ^† 1	9/4089 (0.22%)	16/4090 (0.39%)
Cardiac failure ^† 1	7/4089 (0.17%)	8/4090 (0.20%)
Acute coronary syndrome ^† 1	6/4089 (0.15%)	4/4090 (0.10%)
Myocardial infarction ^† 1	4/4089 (0.10%)	12/4090 (0.29%)
Cardiac arrest ^† 1	4/4089 (0.10%)	9/4090 (0.22%)
Myocardial ischaemia ^† 1	4/4089 (0.10%)	4/4090 (0.10%)
Cardiomyopathy ^† 1	4/4089 (0.10%)	2/4090 (0.05%)
Mitral valve incompetence ^† 1	4/4089 (0.10%)	2/4090 (0.05%)
Ischaemic cardiomyopathy ^† 1	3/4089 (0.07%)	3/4090 (0.07%)
Arrhythmia ^† 1	3/4089 (0.07%)	2/4090 (0.05%)
Palpitations ^† 1	3/4089 (0.07%)	1/4090 (0.02%)
Cardiac failure acute ^† 1	3/4089 (0.07%)	0/4090 (0.00%)
Ventricular arrhythmia ^† 1	3/4089 (0.07%)	0/4090 (0.00%)
Cardiogenic shock ^† 1	2/4089 (0.05%)	3/4090 (0.07%)
Pericarditis ^† 1	2/4089 (0.05%)	3/4090 (0.07%)
Ventricular tachycardia ^† 1	2/4089 (0.05%)	1/4090 (0.02%)
Left ventricular failure ^† 1	2/4089 (0.05%)	0/4090 (0.00%)
Supraventricular extrasystoles ^† 1	2/4089 (0.05%)	0/4090 (0.00%)
Acute myocardial infarction ^† 1	1/4089 (0.02%)	4/4090 (0.10%)
Atrial flutter ^† 1	1/4089 (0.02%)	3/4090 (0.07%)
Aortic valve incompetence ^† 1	1/4089 (0.02%)	2/4090 (0.05%)
Arteriosclerosis coronary artery ^† 1	1/4089 (0.02%)	2/4090 (0.05%)
Coronary artery stenosis ^† 1	1/4089 (0.02%)	2/4090 (0.05%)
Left ventricular dysfunction ^† 1	1/4089 (0.02%)	2/4090 (0.05%)
Bradycardia ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Cardiac failure chronic ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Atrioventricular block complete ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Atrioventricular block second degree ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Bundle branch block left ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Cardiac valve disease ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Cor pulmonale chronic ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Hypertensive heart disease ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Pleuropericarditis ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Sinus node dysfunction ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Ventricular parasystole ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Cardio-respiratory arrest ^† 1	0/4089 (0.00%)	4/4090 (0.10%)
Cardiac tamponade ^† 1	0/4089 (0.00%)	3/4090 (0.07%)
Arteriospasm coronary ^† 1	0/4089 (0.00%)	2/4090 (0.05%)
Pericardial effusion ^† 1	0/4089 (0.00%)	2/4090 (0.05%)
Silent myocardial infarction ^† 1	0/4089 (0.00%)	2/4090 (0.05%)
Ventricular fibrillation ^† 1	0/4089 (0.00%)	2/4090 (0.05%)
Aortic valve disease ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Aortic valve disease mixed ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Cardiac ventricular thrombosis ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Congestive cardiomyopathy ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Coronary artery dissection ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Coronary artery occlusion ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Microvascular coronary artery disease ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Pericardial haemorrhage ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Stress cardiomyopathy ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Tachycardia paroxysmal ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Congenital, familial and genetic disorders
Hypertrophic cardiomyopathy ^† 1	2/4089 (0.05%)	0/4090 (0.00%)
Pancreas divisum ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Ear and labyrinth disorders
Vertigo ^† 1	5/4089 (0.12%)	8/4090 (0.20%)
Vertigo positional ^† 1	2/4089 (0.05%)	5/4090 (0.12%)
Vestibular disorder ^† 1	0/4089 (0.00%)	2/4090 (0.05%)
Ear pain ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Inner ear disorder ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Sudden hearing loss ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Endocrine disorders
Thyroid mass ^† 1	2/4089 (0.05%)	0/4090 (0.00%)
Hyperthyroidism ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Goitre ^† 1	0/4089 (0.00%)	4/4090 (0.10%)
Addison's disease ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Hypothyroidism ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Inappropriate antidiuretic hormone secretion ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Toxic nodular goitre ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Eye disorders
Cataract ^† 1	4/4089 (0.10%)	5/4090 (0.12%)
Retinal detachment ^† 1	3/4089 (0.07%)	0/4090 (0.00%)
Eyelid ptosis ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Retinal haemorrhage ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Diplopia ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Eye swelling ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Retinal vein thrombosis ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Retinal artery occlusion ^† 1	0/4089 (0.00%)	2/4090 (0.05%)
Chalazion ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Visual impairment ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Gastrointestinal disorders
Gastrointestinal haemorrhage ^† 1	26/4089 (0.64%)	20/4090 (0.49%)
Small intestinal obstruction ^† 1	16/4089 (0.39%)	12/4090 (0.29%)
Inguinal hernia ^† 1	11/4089 (0.27%)	8/4090 (0.20%)
Rectal haemorrhage ^† 1	10/4089 (0.24%)	6/4090 (0.15%)
Abdominal pain ^† 1	7/4089 (0.17%)	4/4090 (0.10%)
Vomiting ^† 1	7/4089 (0.17%)	4/4090 (0.10%)
Constipation ^† 1	6/4089 (0.15%)	8/4090 (0.20%)
Colitis ^† 1	6/4089 (0.15%)	6/4090 (0.15%)
Abdominal pain upper ^† 1	5/4089 (0.12%)	6/4090 (0.15%)
Diarrhoea ^† 1	5/4089 (0.12%)	6/4090 (0.15%)
Lower gastrointestinal haemorrhage ^† 1	5/4089 (0.12%)	4/4090 (0.10%)
Colitis ischaemic ^† 1	5/4089 (0.12%)	1/4090 (0.02%)
Gastric ulcer ^† 1	5/4089 (0.12%)	1/4090 (0.02%)
Ileus ^† 1	4/4089 (0.10%)	5/4090 (0.12%)
Large intestine polyp ^† 1	4/4089 (0.10%)	5/4090 (0.12%)
Pancreatitis acute ^† 1	4/4089 (0.10%)	5/4090 (0.12%)
Gastrooesophageal reflux disease ^† 1	4/4089 (0.10%)	2/4090 (0.05%)
Nausea ^† 1	4/4089 (0.10%)	0/4090 (0.00%)
Pancreatitis ^† 1	3/4089 (0.07%)	7/4090 (0.17%)
Abdominal hernia ^† 1	3/4089 (0.07%)	6/4090 (0.15%)
Melaena ^† 1	3/4089 (0.07%)	4/4090 (0.10%)
Diverticulum intestinal haemorrhagic ^† 1	3/4089 (0.07%)	3/4090 (0.07%)
Upper gastrointestinal haemorrhage ^† 1	3/4089 (0.07%)	3/4090 (0.07%)
Haemorrhoids ^† 1	3/4089 (0.07%)	2/4090 (0.05%)
Ascites ^† 1	3/4089 (0.07%)	1/4090 (0.02%)
Diverticulum ^† 1	3/4089 (0.07%)	1/4090 (0.02%)
Gastric ulcer haemorrhage ^† 1	3/4089 (0.07%)	1/4090 (0.02%)
Haemorrhoidal haemorrhage ^† 1	3/4089 (0.07%)	1/4090 (0.02%)
Haematemesis ^† 1	3/4089 (0.07%)	0/4090 (0.00%)
Hiatus hernia ^† 1	2/4089 (0.05%)	5/4090 (0.12%)
Obstructive pancreatitis ^† 1	2/4089 (0.05%)	4/4090 (0.10%)
Intestinal ischaemia ^† 1	2/4089 (0.05%)	3/4090 (0.07%)
Duodenal ulcer ^† 1	2/4089 (0.05%)	2/4090 (0.05%)
Anal fistula ^† 1	2/4089 (0.05%)	1/4090 (0.02%)
Large intestine perforation ^† 1	2/4089 (0.05%)	1/4090 (0.02%)
Peptic ulcer ^† 1	2/4089 (0.05%)	1/4090 (0.02%)
Duodenal ulcer haemorrhage ^† 1	2/4089 (0.05%)	0/4090 (0.00%)
Enteritis ^† 1	2/4089 (0.05%)	0/4090 (0.00%)
Gastritis erosive ^† 1	2/4089 (0.05%)	0/4090 (0.00%)
Pancreatitis chronic ^† 1	2/4089 (0.05%)	0/4090 (0.00%)
Retroperitoneal fibrosis ^† 1	2/4089 (0.05%)	0/4090 (0.00%)
Umbilical hernia ^† 1	1/4089 (0.02%)	10/4090 (0.24%)
Gastric haemorrhage ^† 1	1/4089 (0.02%)	3/4090 (0.07%)
Haematochezia ^† 1	1/4089 (0.02%)	2/4090 (0.05%)
Diverticular perforation ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Diverticulum intestinal ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Faeces discoloured ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Gastric polyps ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Intestinal obstruction ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Large intestinal haemorrhage ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Peritoneal disorder ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Appendix disorder ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Chronic gastritis ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Duodenogastric reflux ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Dyspepsia ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Gastric antral vascular ectasia ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Gastrointestinal angiodysplasia haemorrhagic ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Gastrointestinal pain ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Intestinal perforation ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Intra-abdominal haemorrhage ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Mallory-Weiss syndrome ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Pancreatic cyst ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Pancreatitis haemorrhagic ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Peptic ulcer haemorrhage ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Peritoneal adhesions ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Pharyngo-oesophageal diverticulum ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Proctitis ulcerative ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Rectal prolapse ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Retroperitoneal haemorrhage ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Subileus ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Thrombosis mesenteric vessel ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Volvulus ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Gastritis ^† 1	0/4089 (0.00%)	6/4090 (0.15%)
Dysphagia ^† 1	0/4089 (0.00%)	2/4090 (0.05%)
Food poisoning ^† 1	0/4089 (0.00%)	2/4090 (0.05%)
Gastrointestinal obstruction ^† 1	0/4089 (0.00%)	2/4090 (0.05%)
Impaired gastric emptying ^† 1	0/4089 (0.00%)	2/4090 (0.05%)
Oesophagitis ^† 1	0/4089 (0.00%)	2/4090 (0.05%)
Abdominal adhesions ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Abdominal hernia obstructive ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Colitis ulcerative ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Crohn's disease ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Duodenal perforation ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Duodenitis haemorrhagic ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Enterovesical fistula ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Epigastric discomfort ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Gastric perforation ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Gastric ulcer perforation ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Gastroduodenitis ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Gastrointestinal angiodysplasia ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Gastrointestinal inflammation ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Irritable bowel syndrome ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Mesenteric arterial occlusion ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Mouth haemorrhage ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Oesophageal food impaction ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Oesophageal haemorrhage ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Oesophageal pain ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Pancreatic mass ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Portal hypertensive gastropathy ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Rectal polyp ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Retroperitoneal haematoma ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Strangulated umbilical hernia ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
General disorders
Chest pain ^† 1	66/4089 (1.61%)	66/4090 (1.61%)
Non-cardiac chest pain ^† 1	49/4089 (1.20%)	52/4090 (1.27%)
Asthenia ^† 1	6/4089 (0.15%)	8/4090 (0.20%)
Malaise ^† 1	5/4089 (0.12%)	3/4090 (0.07%)
Pyrexia ^† 1	4/4089 (0.10%)	5/4090 (0.12%)
Oedema peripheral ^† 1	3/4089 (0.07%)	2/4090 (0.05%)
Multiple organ dysfunction syndrome ^† 1	2/4089 (0.05%)	1/4090 (0.02%)
General physical health deterioration ^† 1	2/4089 (0.05%)	0/4090 (0.00%)
Systemic inflammatory response syndrome ^† 1	1/4089 (0.02%)	7/4090 (0.17%)
Chest discomfort ^† 1	1/4089 (0.02%)	4/4090 (0.10%)
Fatigue ^† 1	1/4089 (0.02%)	2/4090 (0.05%)
Cyst ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Impaired healing ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Adverse drug reaction ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Chills ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Complication associated with device ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Drowning ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Gait disturbance ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Generalised oedema ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Peripheral swelling ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Swelling ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Ulcer ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Ulcer haemorrhage ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Vascular stent restenosis ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Exercise tolerance decreased ^† 1	0/4089 (0.00%)	3/4090 (0.07%)
Incarcerated hernia ^† 1	0/4089 (0.00%)	2/4090 (0.05%)
Polyp ^† 1	0/4089 (0.00%)	2/4090 (0.05%)
Catheter site haemorrhage ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Death ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Pain ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Pelvic mass ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Suprapubic pain ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Hepatobiliary disorders
Cholelithiasis ^† 1	15/4089 (0.37%)	18/4090 (0.44%)
Cholecystitis acute ^† 1	15/4089 (0.37%)	7/4090 (0.17%)
Cholecystitis ^† 1	9/4089 (0.22%)	7/4090 (0.17%)
Cholangitis ^† 1	4/4089 (0.10%)	1/4090 (0.02%)
Bile duct stone ^† 1	3/4089 (0.07%)	2/4090 (0.05%)
Jaundice cholestatic ^† 1	3/4089 (0.07%)	0/4090 (0.00%)
Cholecystitis chronic ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Ischaemic hepatitis ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Alcoholic liver disease ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Cryptogenic cirrhosis ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Gallbladder polyp ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Hepatic steatosis ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Gallbladder disorder ^† 1	0/4089 (0.00%)	2/4090 (0.05%)
Gallbladder enlargement ^† 1	0/4089 (0.00%)	2/4090 (0.05%)
Hepatic cirrhosis ^† 1	0/4089 (0.00%)	2/4090 (0.05%)
Biliary colic ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Biliary dilatation ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Cholestasis ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Liver disorder ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Non-alcoholic steatohepatitis ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Immune system disorders
Anaphylactic shock ^† 1	1/4089 (0.02%)	2/4090 (0.05%)
Hypersensitivity ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Allergy to arthropod sting ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Anaphylactic reaction ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Sarcoidosis ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Infections and infestations
Pneumonia ^† 1	105/4089 (2.57%)	118/4090 (2.89%)
Cellulitis ^† 1	36/4089 (0.88%)	28/4090 (0.68%)
Sepsis ^† 1	25/4089 (0.61%)	31/4090 (0.76%)
Urinary tract infection ^† 1	25/4089 (0.61%)	22/4090 (0.54%)
Gastroenteritis ^† 1	16/4089 (0.39%)	16/4090 (0.39%)
Erysipelas ^† 1	13/4089 (0.32%)	3/4090 (0.07%)
Osteomyelitis ^† 1	12/4089 (0.29%)	7/4090 (0.17%)
Septic shock ^† 1	12/4089 (0.29%)	3/4090 (0.07%)
Bronchitis ^† 1	11/4089 (0.27%)	10/4090 (0.24%)
Diverticulitis ^† 1	11/4089 (0.27%)	9/4090 (0.22%)
Urosepsis ^† 1	11/4089 (0.27%)	9/4090 (0.22%)
Appendicitis ^† 1	9/4089 (0.22%)	6/4090 (0.15%)
Postoperative wound infection ^† 1	8/4089 (0.20%)	4/4090 (0.10%)
Pyelonephritis ^† 1	7/4089 (0.17%)	4/4090 (0.10%)
Gastroenteritis viral ^† 1	5/4089 (0.12%)	1/4090 (0.02%)
Arthritis bacterial ^† 1	4/4089 (0.10%)	2/4090 (0.05%)
Wound infection ^† 1	4/4089 (0.10%)	2/4090 (0.05%)
Bacteraemia ^† 1	3/4089 (0.07%)	4/4090 (0.10%)
Cystitis ^† 1	3/4089 (0.07%)	3/4090 (0.07%)
Localised infection ^† 1	3/4089 (0.07%)	3/4090 (0.07%)
Arthritis infective ^† 1	3/4089 (0.07%)	2/4090 (0.05%)
Staphylococcal infection ^† 1	3/4089 (0.07%)	2/4090 (0.05%)
Abscess limb ^† 1	3/4089 (0.07%)	1/4090 (0.02%)
Gangrene ^† 1	3/4089 (0.07%)	1/4090 (0.02%)
Intervertebral discitis ^† 1	3/4089 (0.07%)	1/4090 (0.02%)
Laryngitis ^† 1	3/4089 (0.07%)	0/4090 (0.00%)
Influenza ^† 1	2/4089 (0.05%)	4/4090 (0.10%)
Pyelonephritis acute ^† 1	2/4089 (0.05%)	4/4090 (0.10%)
Anal abscess ^† 1	2/4089 (0.05%)	2/4090 (0.05%)
Herpes zoster ^† 1	2/4089 (0.05%)	1/4090 (0.02%)
Infective exacerbation of chronic obstructive airways disease ^† 1	2/4089 (0.05%)	1/4090 (0.02%)
Liver abscess ^† 1	2/4089 (0.05%)	1/4090 (0.02%)
Appendicitis perforated ^† 1	2/4089 (0.05%)	0/4090 (0.00%)
Meningitis bacterial ^† 1	2/4089 (0.05%)	0/4090 (0.00%)
Necrotising fasciitis ^† 1	2/4089 (0.05%)	0/4090 (0.00%)
Parainfluenzae virus infection ^† 1	2/4089 (0.05%)	0/4090 (0.00%)
Perirectal abscess ^† 1	2/4089 (0.05%)	0/4090 (0.00%)
Pneumococcal sepsis ^† 1	2/4089 (0.05%)	0/4090 (0.00%)
Pneumonia streptococcal ^† 1	2/4089 (0.05%)	0/4090 (0.00%)
Pulmonary tuberculosis ^† 1	2/4089 (0.05%)	0/4090 (0.00%)
Lower respiratory tract infection ^† 1	1/4089 (0.02%)	5/4090 (0.12%)
Upper respiratory tract infection ^† 1	1/4089 (0.02%)	5/4090 (0.12%)
Endocarditis ^† 1	1/4089 (0.02%)	4/4090 (0.10%)
Viral infection ^† 1	1/4089 (0.02%)	3/4090 (0.07%)
Abscess intestinal ^† 1	1/4089 (0.02%)	2/4090 (0.05%)
Clostridium difficile infection ^† 1	1/4089 (0.02%)	2/4090 (0.05%)
Implant site infection ^† 1	1/4089 (0.02%)	2/4090 (0.05%)
Peritonitis ^† 1	1/4089 (0.02%)	2/4090 (0.05%)
Pneumonia staphylococcal ^† 1	1/4089 (0.02%)	2/4090 (0.05%)
Bronchitis viral ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Escherichia urinary tract infection ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Gastroenteritis rotavirus ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Pneumonia influenzal ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Pneumonia pseudomonal ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Postoperative abscess ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Respiratory syncytial virus infection ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Streptococcal sepsis ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Tracheobronchitis ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Acquired immunodeficiency syndrome ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Bronchiolitis ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Bronchitis bacterial ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Campylobacter gastroenteritis ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Catheter site cellulitis ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Cellulitis streptococcal ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Clostridium difficile colitis ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Cystitis bacterial ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Cystitis escherichia ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Cytomegalovirus infection ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Dengue fever ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Device related sepsis ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Diabetic foot infection ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Diarrhoea infectious ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Epiglottitis ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Gastrointestinal bacterial overgrowth ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Gastrointestinal infection ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Genital infection fungal ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Graft infection ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Groin abscess ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Hepatitis C ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Incision site abscess ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Infected skin ulcer ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Infectious colitis ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Infective exacerbation of bronchiectasis ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Joint abscess ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Keratitis bacterial ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Latent tuberculosis ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Lower respiratory tract infection viral ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Mastitis ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Meningitis ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Mycobacterial infection ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Parotitis ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Peritonitis bacterial ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Pharyngolaryngeal abscess ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Pilonidal cyst ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Pneumonia bacterial ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Post procedural infection ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Rectal abscess ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Respiratory tract infection ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Shunt infection ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Skin infection ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Staphylococcal bacteraemia ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Staphylococcal sepsis ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Subacute endocarditis ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Systemic candida ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Tick-borne fever ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Viral sepsis ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Viral upper respiratory tract infection ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Vulval cellulitis ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Wound sepsis ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Infection ^† 1	0/4089 (0.00%)	2/4090 (0.05%)
Orchitis ^† 1	0/4089 (0.00%)	2/4090 (0.05%)
Rotavirus infection ^† 1	0/4089 (0.00%)	2/4090 (0.05%)
Abdominal abscess ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Abdominal infection ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Abdominal wall abscess ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Bacterial sepsis ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Biliary abscess ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Breast abscess ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Bursitis infective ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Cholecystitis infective ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Device related infection ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Diverticulitis intestinal haemorrhagic ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Enterococcal bacteraemia ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Epididymitis ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Gas gangrene ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
H1N1 influenza ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Helicobacter gastritis ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Hepatitis viral ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Klebsiella infection ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Listeriosis ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Neutropenic sepsis ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Oral candidiasis ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Osteomyelitis acute ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Otitis media acute ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Parasitic gastroenteritis ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Pelvic abscess ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Pharyngeal abscess ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Pneumonia respiratory syncytial viral ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Pneumonia viral ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Post procedural cellulitis ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Pseudomembranous colitis ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Pseudomonas infection ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Pyelocystitis ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Respiratory tract infection viral ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Rhinovirus infection ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Sepsis syndrome ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Sialoadenitis ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Streptococcal bacteraemia ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Streptococcal infection ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Tooth abscess ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Wound abscess ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Wound infection staphylococcal ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Injury, poisoning and procedural complications
Fall ^† 1	16/4089 (0.39%)	15/4090 (0.37%)
Subdural haematoma ^† 1	9/4089 (0.22%)	5/4090 (0.12%)
Hip fracture ^† 1	8/4089 (0.20%)	8/4090 (0.20%)
Incisional hernia ^† 1	6/4089 (0.15%)	3/4090 (0.07%)
Post procedural haemorrhage ^† 1	5/4089 (0.12%)	3/4090 (0.07%)
Rib fracture ^† 1	5/4089 (0.12%)	3/4090 (0.07%)
Head injury ^† 1	5/4089 (0.12%)	2/4090 (0.05%)
Femur fracture ^† 1	4/4089 (0.10%)	10/4090 (0.24%)
Ankle fracture ^† 1	4/4089 (0.10%)	5/4090 (0.12%)
Tendon rupture ^† 1	4/4089 (0.10%)	4/4090 (0.10%)
Lumbar vertebral fracture ^† 1	4/4089 (0.10%)	1/4090 (0.02%)
Humerus fracture ^† 1	3/4089 (0.07%)	4/4090 (0.10%)
Road traffic accident ^† 1	3/4089 (0.07%)	4/4090 (0.10%)
Laceration ^† 1	3/4089 (0.07%)	0/4090 (0.00%)
Multiple injuries ^† 1	3/4089 (0.07%)	0/4090 (0.00%)
Joint dislocation ^† 1	2/4089 (0.05%)	3/4090 (0.07%)
Spinal fracture ^† 1	2/4089 (0.05%)	2/4090 (0.05%)
Tibia fracture ^† 1	2/4089 (0.05%)	2/4090 (0.05%)
Ligament injury ^† 1	2/4089 (0.05%)	1/4090 (0.02%)
Postoperative ileus ^† 1	2/4089 (0.05%)	1/4090 (0.02%)
Subarachnoid haemorrhage ^† 1	2/4089 (0.05%)	1/4090 (0.02%)
Subdural haemorrhage ^† 1	2/4089 (0.05%)	1/4090 (0.02%)
Thoracic vertebral fracture ^† 1	2/4089 (0.05%)	1/4090 (0.02%)
Traumatic haematoma ^† 1	2/4089 (0.05%)	1/4090 (0.02%)
Clavicle fracture ^† 1	2/4089 (0.05%)	0/4090 (0.00%)
Lower limb fracture ^† 1	2/4089 (0.05%)	0/4090 (0.00%)
Muscle rupture ^† 1	2/4089 (0.05%)	0/4090 (0.00%)
Muscle strain ^† 1	2/4089 (0.05%)	0/4090 (0.00%)
Postoperative fever ^† 1	2/4089 (0.05%)	0/4090 (0.00%)
Postoperative hernia ^† 1	2/4089 (0.05%)	0/4090 (0.00%)
Wound dehiscence ^† 1	2/4089 (0.05%)	0/4090 (0.00%)
Craniocerebral injury ^† 1	1/4089 (0.02%)	3/4090 (0.07%)
Femoral neck fracture ^† 1	1/4089 (0.02%)	2/4090 (0.05%)
Pelvic fracture ^† 1	1/4089 (0.02%)	2/4090 (0.05%)
Concussion ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Fibula fracture ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Fractured sacrum ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Limb injury ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Post procedural discharge ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Post procedural haematoma ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Post procedural swelling ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Ulna fracture ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Wound ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Accidental overdose ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Avulsion fracture ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Bone fragmentation ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Cartilage injury ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Chest injury ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Dislocation of sternum ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Foot fracture ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Foreign body in gastrointestinal tract ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Fracture ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Hand fracture ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Incarcerated incisional hernia ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Multiple fractures ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Muscle injury ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Overdose ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Patella fracture ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Periprosthetic fracture ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Post laminectomy syndrome ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Post procedural pulmonary embolism ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Postoperative adhesion ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Postoperative renal failure ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Postoperative thrombosis ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Radiation oesophagitis ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Spinal cord injury ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Toxicity to various agents ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Traumatic liver injury ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Procedural pain ^† 1	0/4089 (0.00%)	3/4090 (0.07%)
Alcohol poisoning ^† 1	0/4089 (0.00%)	2/4090 (0.05%)
Brain contusion ^† 1	0/4089 (0.00%)	2/4090 (0.05%)
Jaw fracture ^† 1	0/4089 (0.00%)	2/4090 (0.05%)
Meniscus injury ^† 1	0/4089 (0.00%)	2/4090 (0.05%)
Spinal compression fracture ^† 1	0/4089 (0.00%)	2/4090 (0.05%)
Stomal hernia ^† 1	0/4089 (0.00%)	2/4090 (0.05%)
Anaemia postoperative ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Axillary nerve injury ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Back injury ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Carbon monoxide poisoning ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Cervical vertebral fracture ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Compression fracture ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Facial bones fracture ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Forearm fracture ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Gastrointestinal stoma complication ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Heat stroke ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Oesophageal injury ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Poisoning deliberate ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Post procedural complication ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Post procedural haematuria ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Procedural hypertension ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Pubis fracture ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Radiation injury ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Sciatic nerve injury ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Skull fractured base ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Spinal column injury ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Stress fracture ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Thermal burn ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Traumatic intracranial haemorrhage ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Traumatic renal injury ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Upper limb fracture ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Ureteric anastomosis complication ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Urethral injury ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Vascular pseudoaneurysm ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Investigations
Troponin increased ^† 1	2/4089 (0.05%)	3/4090 (0.07%)
Arteriogram coronary ^† 1	2/4089 (0.05%)	1/4090 (0.02%)
Ejection fraction decreased ^† 1	2/4089 (0.05%)	1/4090 (0.02%)
Blood pressure increased ^† 1	1/4089 (0.02%)	2/4090 (0.05%)
Blood glucose increased ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Weight decreased ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Biopsy pleura ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Prostatic specific antigen increased ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Transaminases increased ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Influenza A virus test positive ^† 1	0/4089 (0.00%)	3/4090 (0.07%)
Alanine aminotransferase increased ^† 1	0/4089 (0.00%)	2/4090 (0.05%)
Anticoagulation drug level above therapeutic ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Blood pressure difference of extremities ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Cardiac murmur ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Ejection fraction abnormal ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Electrocardiogram T wave abnormal ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Influenza virus test positive ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Lipase increased ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Metabolism and nutrition disorders
Dehydration ^† 1	16/4089 (0.39%)	11/4090 (0.27%)
Hypoglycaemia ^† 1	15/4089 (0.37%)	14/4090 (0.34%)
Diabetes mellitus ^† 1	11/4089 (0.27%)	8/4090 (0.20%)
Hyperglycaemia ^† 1	10/4089 (0.24%)	8/4090 (0.20%)
Obesity ^† 1	9/4089 (0.22%)	5/4090 (0.12%)
Diabetes mellitus inadequate control ^† 1	5/4089 (0.12%)	3/4090 (0.07%)
Hypomagnesaemia ^† 1	5/4089 (0.12%)	0/4090 (0.00%)
Diabetic ketoacidosis ^† 1	4/4089 (0.10%)	1/4090 (0.02%)
Hyperkalaemia ^† 1	3/4089 (0.07%)	6/4090 (0.15%)
Hypokalaemia ^† 1	3/4089 (0.07%)	3/4090 (0.07%)
Type 2 diabetes mellitus ^† 1	2/4089 (0.05%)	4/4090 (0.10%)
Hyponatraemia ^† 1	2/4089 (0.05%)	3/4090 (0.07%)
Metabolic acidosis ^† 1	2/4089 (0.05%)	3/4090 (0.07%)
Hypocalcaemia ^† 1	2/4089 (0.05%)	1/4090 (0.02%)
Hypovolaemia ^† 1	2/4089 (0.05%)	1/4090 (0.02%)
Gout ^† 1	2/4089 (0.05%)	0/4090 (0.00%)
Lactic acidosis ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Acidosis ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Failure to thrive ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Hypercalcaemia ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Hyperglycaemic hyperosmolar nonketotic syndrome ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Hypophosphataemia ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Shock hypoglycaemic ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Tumour lysis syndrome ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Diabetic metabolic decompensation ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Electrolyte imbalance ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Hypernatraemia ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Hyperosmolar state ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Iron deficiency ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Musculoskeletal and connective tissue disorders
Osteoarthritis ^† 1	81/4089 (1.98%)	73/4090 (1.78%)
Back pain ^† 1	17/4089 (0.42%)	11/4090 (0.27%)
Intervertebral disc protrusion ^† 1	16/4089 (0.39%)	7/4090 (0.17%)
Spinal column stenosis ^† 1	11/4089 (0.27%)	5/4090 (0.12%)
Rotator cuff syndrome ^† 1	10/4089 (0.24%)	12/4090 (0.29%)
Lumbar spinal stenosis ^† 1	10/4089 (0.24%)	10/4090 (0.24%)
Arthralgia ^† 1	7/4089 (0.17%)	9/4090 (0.22%)
Arthritis ^† 1	6/4089 (0.15%)	6/4090 (0.15%)
Musculoskeletal chest pain ^† 1	6/4089 (0.15%)	1/4090 (0.02%)
Musculoskeletal pain ^† 1	5/4089 (0.12%)	3/4090 (0.07%)
Pain in extremity ^† 1	5/4089 (0.12%)	2/4090 (0.05%)
Spinal osteoarthritis ^† 1	3/4089 (0.07%)	3/4090 (0.07%)
Spondylolisthesis ^† 1	3/4089 (0.07%)	2/4090 (0.05%)
Foot deformity ^† 1	2/4089 (0.05%)	4/4090 (0.10%)
Intervertebral disc degeneration ^† 1	2/4089 (0.05%)	3/4090 (0.07%)
Bursitis ^† 1	2/4089 (0.05%)	2/4090 (0.05%)
Rhabdomyolysis ^† 1	2/4089 (0.05%)	1/4090 (0.02%)
Cervical spinal stenosis ^† 1	1/4089 (0.02%)	4/4090 (0.10%)
Vertebral foraminal stenosis ^† 1	1/4089 (0.02%)	2/4090 (0.05%)
Flank pain ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Muscular weakness ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Osteonecrosis ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Polymyalgia rheumatica ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Pseudarthrosis ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Gouty arthritis ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Intervertebral disc compression ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Knee deformity ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Mandibular mass ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Mobility decreased ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Muscle spasms ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Neck pain ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Osteochondrosis ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Pathological fracture ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Periarthritis ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Rheumatic fever ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Soft tissue mass ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Sympathetic posterior cervical syndrome ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Synovial cyst ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Tendonitis ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Costochondritis ^† 1	0/4089 (0.00%)	5/4090 (0.12%)
Rheumatoid arthritis ^† 1	0/4089 (0.00%)	3/4090 (0.07%)
Exostosis ^† 1	0/4089 (0.00%)	2/4090 (0.05%)
Arthropathy ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Back disorder ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Coccydynia ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Gouty tophus ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Haemarthrosis ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Intervertebral disc disorder ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Joint range of motion decreased ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Myalgia ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Pain in jaw ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Systemic lupus erythematosus ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Temporomandibular joint syndrome ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer ^† 1	26/4089 (0.64%)	26/4090 (0.64%)
Breast cancer ^† 1	14/4089 (0.34%)	8/4090 (0.20%)
Colon cancer ^† 1	10/4089 (0.24%)	6/4090 (0.15%)
Lung neoplasm malignant ^† 1	8/4089 (0.20%)	14/4090 (0.34%)
Bladder cancer ^† 1	8/4089 (0.20%)	9/4090 (0.22%)
Lung cancer metastatic ^† 1	8/4089 (0.20%)	9/4090 (0.22%)
Malignant melanoma ^† 1	7/4089 (0.17%)	4/4090 (0.10%)
Adenocarcinoma of colon ^† 1	6/4089 (0.15%)	6/4090 (0.15%)
Pancreatic carcinoma ^† 1	6/4089 (0.15%)	4/4090 (0.10%)
Renal cancer ^† 1	6/4089 (0.15%)	4/4090 (0.10%)
Prostate cancer metastatic ^† 1	5/4089 (0.12%)	5/4090 (0.12%)
Bladder transitional cell carcinoma ^† 1	5/4089 (0.12%)	4/4090 (0.10%)
Pancreatic carcinoma metastatic ^† 1	5/4089 (0.12%)	2/4090 (0.05%)
Lung adenocarcinoma ^† 1	4/4089 (0.10%)	6/4090 (0.15%)
Squamous cell carcinoma of lung ^† 1	4/4089 (0.10%)	5/4090 (0.12%)
Gastric cancer ^† 1	4/4089 (0.10%)	3/4090 (0.07%)
Metastases to liver ^† 1	4/4089 (0.10%)	3/4090 (0.07%)
Squamous cell carcinoma ^† 1	4/4089 (0.10%)	3/4090 (0.07%)
Basal cell carcinoma ^† 1	3/4089 (0.07%)	2/4090 (0.05%)
Bladder neoplasm ^† 1	3/4089 (0.07%)	2/4090 (0.05%)
Cancer pain ^† 1	3/4089 (0.07%)	1/4090 (0.02%)
Hepatic cancer ^† 1	3/4089 (0.07%)	1/4090 (0.02%)
Metastases to lung ^† 1	3/4089 (0.07%)	0/4090 (0.00%)
Non-small cell lung cancer metastatic ^† 1	3/4089 (0.07%)	0/4090 (0.00%)
Rectal cancer ^† 1	2/4089 (0.05%)	6/4090 (0.15%)
Non-small cell lung cancer ^† 1	2/4089 (0.05%)	3/4090 (0.07%)
Colon cancer metastatic ^† 1	2/4089 (0.05%)	2/4090 (0.05%)
Endometrial cancer ^† 1	2/4089 (0.05%)	2/4090 (0.05%)
Non-Hodgkin's lymphoma ^† 1	2/4089 (0.05%)	2/4090 (0.05%)
Prostate cancer recurrent ^† 1	2/4089 (0.05%)	2/4090 (0.05%)
Rectal adenocarcinoma ^† 1	2/4089 (0.05%)	2/4090 (0.05%)
Transitional cell carcinoma ^† 1	2/4089 (0.05%)	2/4090 (0.05%)
Breast cancer metastatic ^† 1	2/4089 (0.05%)	1/4090 (0.02%)
Cervix carcinoma ^† 1	2/4089 (0.05%)	1/4090 (0.02%)
Meningioma ^† 1	2/4089 (0.05%)	1/4090 (0.02%)
Metastases to bone ^† 1	2/4089 (0.05%)	1/4090 (0.02%)
Parathyroid tumour benign ^† 1	2/4089 (0.05%)	1/4090 (0.02%)
Renal cancer metastatic ^† 1	2/4089 (0.05%)	1/4090 (0.02%)
Bladder cancer recurrent ^† 1	2/4089 (0.05%)	0/4090 (0.00%)
Brain neoplasm ^† 1	2/4089 (0.05%)	0/4090 (0.00%)
Breast cancer recurrent ^† 1	2/4089 (0.05%)	0/4090 (0.00%)
Chronic lymphocytic leukaemia ^† 1	2/4089 (0.05%)	0/4090 (0.00%)
Invasive ductal breast carcinoma ^† 1	2/4089 (0.05%)	0/4090 (0.00%)
Malignant melanoma in situ ^† 1	2/4089 (0.05%)	0/4090 (0.00%)
Metastatic renal cell carcinoma ^† 1	2/4089 (0.05%)	0/4090 (0.00%)
Renal neoplasm ^† 1	2/4089 (0.05%)	0/4090 (0.00%)
Colon adenoma ^† 1	1/4089 (0.02%)	4/4090 (0.10%)
Acute myeloid leukaemia ^† 1	1/4089 (0.02%)	3/4090 (0.07%)
Colon neoplasm ^† 1	1/4089 (0.02%)	3/4090 (0.07%)
Renal cell carcinoma ^† 1	1/4089 (0.02%)	2/4090 (0.05%)
Bone cancer ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Colon cancer recurrent ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Colorectal cancer ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Endometrial adenocarcinoma ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Gastrointestinal stromal tumour ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Lipoma ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Metastases to peritoneum ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Metastatic carcinoma of the bladder ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Mucinous adenocarcinoma of appendix ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Myelodysplastic syndrome ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Oesophageal carcinoma ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Pancreatic neoplasm ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Plasma cell myeloma ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Prostatic adenoma ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Small cell lung cancer ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Thyroid cancer metastatic ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Uterine cancer ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Adenocarcinoma ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Adenocarcinoma gastric ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Anal cancer ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
B-cell lymphoma ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Benign neoplasm of thyroid gland ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Breast cancer male ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Cervix neoplasm ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Cholangiocarcinoma ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Cholesteatoma ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Colorectal adenocarcinoma ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Diffuse large B-cell lymphoma ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Endometrial cancer stage I ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Extranodal marginal zone B-cell lymphoma ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Gastrointestinal stromal cancer ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Hepatocellular carcinoma ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Iris melanoma ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Large cell lung cancer metastatic ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Large intestine benign neoplasm ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Leiomyosarcoma ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Lung adenocarcinoma stage IV ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Lung carcinoma cell type unspecified recurrent ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Malignant glioma ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Metastases to abdominal cavity ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Metastases to chest wall ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Metastases to kidney ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Metastasis ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Metastatic gastric cancer ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Metastatic squamous cell carcinoma ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Nasal neoplasm ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Oesophageal neoplasm ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Oropharyngeal cancer ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Ovarian epithelial cancer ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Ovarian granulosa-theca cell tumour ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Pituitary tumour ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Pleural mesothelioma ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Salivary gland adenoma ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Small cell lung cancer metastatic ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Small intestine carcinoma ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Squamous cell carcinoma of skin ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Testis cancer ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Thyroid cancer ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Transitional cell cancer of the renal pelvis and ureter ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Tumour ulceration ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Uterine leiomyoma ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Breast cancer stage I ^† 1	0/4089 (0.00%)	2/4090 (0.05%)
Clear cell renal cell carcinoma ^† 1	0/4089 (0.00%)	2/4090 (0.05%)
Laryngeal cancer ^† 1	0/4089 (0.00%)	2/4090 (0.05%)
Lymphocytic leukaemia ^† 1	0/4089 (0.00%)	2/4090 (0.05%)
Metastases to central nervous system ^† 1	0/4089 (0.00%)	2/4090 (0.05%)
Acute lymphocytic leukaemia ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Adenoid cystic carcinoma ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Adrenal adenoma ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Adrenal neoplasm ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Anal squamous cell carcinoma ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Bladder cancer stage III ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Central nervous system neoplasm ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Colorectal cancer metastatic ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Duodenal neoplasm ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Endometrial cancer metastatic ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Gastric adenoma ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Gastric cancer recurrent ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Gastric neoplasm ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Gastrointestinal tract adenoma ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Hepatic cancer metastatic ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Intraductal proliferative breast lesion ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Lip and/or oral cavity cancer ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Lung adenocarcinoma stage II ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Malignant mesenteric neoplasm ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Metastases to lymph nodes ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Metastatic neoplasm ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Mucoepidermoid carcinoma of salivary gland ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Neoplasm malignant ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Neuroendocrine carcinoma of the skin ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Neuroma ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Nodular melanoma ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Non-small cell lung cancer stage III ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Non-small cell lung cancer stage IV ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Oesophageal cancer metastatic ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Ovarian adenoma ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Ovarian cancer metastatic ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Ovarian epithelial cancer metastatic ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Ovarian neoplasm ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Penile cancer ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Prostate cancer stage IV ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Rectal neoplasm ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Refractory anaemia with ringed sideroblasts ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Refractory cytopenia with unilineage dysplasia ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Retroperitoneal cancer ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Schwannoma ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Skin cancer ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Squamous cell carcinoma of pharynx ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Throat cancer ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Tongue cancer metastatic ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Tonsil cancer ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Transitional cell carcinoma recurrent ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Urethral cancer ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Nervous system disorders
Syncope ^† 1	28/4089 (0.68%)	31/4090 (0.76%)
Dizziness ^† 1	11/4089 (0.27%)	10/4090 (0.24%)
Transient ischaemic attack ^† 1	8/4089 (0.20%)	3/4090 (0.07%)
Encephalopathy ^† 1	7/4089 (0.17%)	2/4090 (0.05%)
Presyncope ^† 1	6/4089 (0.15%)	6/4090 (0.15%)
Cerebrovascular accident ^† 1	3/4089 (0.07%)	5/4090 (0.12%)
Headache ^† 1	3/4089 (0.07%)	4/4090 (0.10%)
Seizure ^† 1	3/4089 (0.07%)	4/4090 (0.10%)
Metabolic encephalopathy ^† 1	2/4089 (0.05%)	3/4090 (0.07%)
Carpal tunnel syndrome ^† 1	2/4089 (0.05%)	1/4090 (0.02%)
Cervical radiculopathy ^† 1	2/4089 (0.05%)	1/4090 (0.02%)
Ataxia ^† 1	2/4089 (0.05%)	0/4090 (0.00%)
Dementia ^† 1	2/4089 (0.05%)	0/4090 (0.00%)
Epilepsy ^† 1	2/4089 (0.05%)	0/4090 (0.00%)
Intracranial aneurysm ^† 1	2/4089 (0.05%)	0/4090 (0.00%)
Lumbar radiculopathy ^† 1	1/4089 (0.02%)	3/4090 (0.07%)
Neuralgia ^† 1	1/4089 (0.02%)	2/4090 (0.05%)
Aphasia ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Cerebral infarction ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Dementia Alzheimer's type ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Facial paralysis ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Hydrocephalus ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Hypertensive encephalopathy ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Neuropathy peripheral ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Transient global amnesia ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Unresponsive to stimuli ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Brain injury ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Carotid artery occlusion ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Cerebrospinal fluid leakage ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Cognitive disorder ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Dural arteriovenous fistula ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Haemorrhagic transformation stroke ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Hypoaesthesia ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
IIIrd nerve paralysis ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Intracranial mass ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Ischaemic stroke ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Migraine ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Nerve compression ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Neurodegenerative disorder ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Neurological symptom ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Pseudoradicular syndrome ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Quadriplegia ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Radicular syndrome ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Sensory ganglionitis ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Speech disorder ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Toxic encephalopathy ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Trigeminal nerve disorder ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Vasogenic cerebral oedema ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Vocal cord paralysis ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Hemiparesis ^† 1	0/4089 (0.00%)	5/4090 (0.12%)
Cerebral haemorrhage ^† 1	0/4089 (0.00%)	2/4090 (0.05%)
Hypoxic-ischaemic encephalopathy ^† 1	0/4089 (0.00%)	2/4090 (0.05%)
Loss of consciousness ^† 1	0/4089 (0.00%)	2/4090 (0.05%)
Sciatica ^† 1	0/4089 (0.00%)	2/4090 (0.05%)
Acute disseminated encephalomyelitis ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Altered state of consciousness ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Amyotrophic lateral sclerosis ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Autonomic nervous system imbalance ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Carotid artery disease ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Demyelinating polyneuropathy ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Diabetic neuropathy ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Haemorrhage intracranial ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Hypoglycaemic coma ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Hypoglycaemic encephalopathy ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Hypoglycaemic unconsciousness ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Multiple sclerosis ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Multiple sclerosis relapse ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Myelopathy ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Paraesthesia ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Polyneuropathy ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Reversible ischaemic neurological deficit ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Spinal cord herniation ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Status epilepticus ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Trigeminal neuralgia ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Vascular dementia ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Product Issues
Device malfunction ^† 1	2/4089 (0.05%)	2/4090 (0.05%)
Device breakage ^† 1	1/4089 (0.02%)	2/4090 (0.05%)
Device dislocation ^† 1	1/4089 (0.02%)	2/4090 (0.05%)
Device failure ^† 1	1/4089 (0.02%)	2/4090 (0.05%)
Device occlusion ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Psychiatric disorders
Delirium ^† 1	5/4089 (0.12%)	2/4090 (0.05%)
Suicide attempt ^† 1	3/4089 (0.07%)	1/4090 (0.02%)
Mental status changes ^† 1	2/4089 (0.05%)	3/4090 (0.07%)
Depression ^† 1	2/4089 (0.05%)	2/4090 (0.05%)
Anxiety ^† 1	2/4089 (0.05%)	0/4090 (0.00%)
Panic attack ^† 1	2/4089 (0.05%)	0/4090 (0.00%)
Alcohol abuse ^† 1	1/4089 (0.02%)	3/4090 (0.07%)
Completed suicide ^† 1	1/4089 (0.02%)	2/4090 (0.05%)
Suicidal ideation ^† 1	1/4089 (0.02%)	2/4090 (0.05%)
Alcohol withdrawal syndrome ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Confusional state ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Aggression ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Agitated depression ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Delirium tremens ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Major depression ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Schizoaffective disorder ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Acute psychosis ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Alcoholism ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Bipolar disorder ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Mania ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Psychotic disorder ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Schizophrenia ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Renal and urinary disorders
Acute kidney injury ^† 1	47/4089 (1.15%)	34/4090 (0.83%)
Nephrolithiasis ^† 1	13/4089 (0.32%)	12/4090 (0.29%)
Renal failure ^† 1	11/4089 (0.27%)	6/4090 (0.15%)
Haematuria ^† 1	8/4089 (0.20%)	4/4090 (0.10%)
Ureterolithiasis ^† 1	6/4089 (0.15%)	7/4090 (0.17%)
Chronic kidney disease ^† 1	6/4089 (0.15%)	4/4090 (0.10%)
Urinary retention ^† 1	5/4089 (0.12%)	4/4090 (0.10%)
Renal impairment ^† 1	5/4089 (0.12%)	1/4090 (0.02%)
Renal cyst ^† 1	4/4089 (0.10%)	0/4090 (0.00%)
Urethral stenosis ^† 1	3/4089 (0.07%)	2/4090 (0.05%)
Urinary tract obstruction ^† 1	3/4089 (0.07%)	1/4090 (0.02%)
Calculus urinary ^† 1	2/4089 (0.05%)	3/4090 (0.07%)
Renal colic ^† 1	2/4089 (0.05%)	3/4090 (0.07%)
End stage renal disease ^† 1	2/4089 (0.05%)	1/4090 (0.02%)
Cystitis haemorrhagic ^† 1	2/4089 (0.05%)	0/4090 (0.00%)
Bladder outlet obstruction ^† 1	1/4089 (0.02%)	2/4090 (0.05%)
Stress urinary incontinence ^† 1	1/4089 (0.02%)	2/4090 (0.05%)
Bladder neck obstruction ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Nephropathy ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Urinary bladder haemorrhage ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Bladder stenosis ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Incontinence ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Renal artery fibromuscular dysplasia ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Renal disorder ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Renal injury ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Tubulointerstitial nephritis ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Ureteric dilatation ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Ureteric stenosis ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Urethral meatus stenosis ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Calculus bladder ^† 1	0/4089 (0.00%)	4/4090 (0.10%)
Urinary incontinence ^† 1	0/4089 (0.00%)	4/4090 (0.10%)
Acute prerenal failure ^† 1	0/4089 (0.00%)	2/4090 (0.05%)
Bladder dysfunction ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Bladder prolapse ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Diabetic nephropathy ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Dysuria ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Hydronephrosis ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Hypertonic bladder ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Nephropathy toxic ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Renal haemorrhage ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Stag horn calculus ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Urinary bladder polyp ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Reproductive system and breast disorders
Benign prostatic hyperplasia ^† 1	18/4089 (0.44%)	11/4090 (0.27%)
Prostatitis ^† 1	6/4089 (0.15%)	3/4090 (0.07%)
Prostatomegaly ^† 1	2/4089 (0.05%)	2/4090 (0.05%)
Adnexa uteri mass ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Genital haemorrhage ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Menorrhagia ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Pelvic prolapse ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Peyronie's disease ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Prostatism ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Vaginal prolapse ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Uterine polyp ^† 1	0/4089 (0.00%)	2/4090 (0.05%)
Endometrial hyperplasia ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Endometrial hypoplasia ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Female genital tract fistula ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Ovarian cyst ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Ovarian cyst ruptured ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Seminal vesicular cyst ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Testicular cyst ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Uterine prolapse ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease ^† 1	33/4089 (0.81%)	34/4090 (0.83%)
Acute respiratory failure ^† 1	19/4089 (0.46%)	18/4090 (0.44%)
Respiratory failure ^† 1	16/4089 (0.39%)	15/4090 (0.37%)
Dyspnoea ^† 1	16/4089 (0.39%)	13/4090 (0.32%)
Pulmonary embolism ^† 1	14/4089 (0.34%)	22/4090 (0.54%)
Asthma ^† 1	9/4089 (0.22%)	5/4090 (0.12%)
Pleural effusion ^† 1	7/4089 (0.17%)	11/4090 (0.27%)
Epistaxis ^† 1	7/4089 (0.17%)	4/4090 (0.10%)
Pneumonia aspiration ^† 1	7/4089 (0.17%)	4/4090 (0.10%)
Dyspnoea exertional ^† 1	4/4089 (0.10%)	2/4090 (0.05%)
Pulmonary fibrosis ^† 1	4/4089 (0.10%)	1/4090 (0.02%)
Pulmonary oedema ^† 1	3/4089 (0.07%)	7/4090 (0.17%)
Hypoxia ^† 1	3/4089 (0.07%)	5/4090 (0.12%)
Pneumothorax ^† 1	3/4089 (0.07%)	2/4090 (0.05%)
Pleurisy ^† 1	3/4089 (0.07%)	1/4090 (0.02%)
Acute respiratory distress syndrome ^† 1	2/4089 (0.05%)	2/4090 (0.05%)
Sleep apnoea syndrome ^† 1	2/4089 (0.05%)	2/4090 (0.05%)
Pulmonary hypertension ^† 1	2/4089 (0.05%)	1/4090 (0.02%)
Pleuritic pain ^† 1	1/4089 (0.02%)	4/4090 (0.10%)
Interstitial lung disease ^† 1	1/4089 (0.02%)	2/4090 (0.05%)
Respiratory distress ^† 1	1/4089 (0.02%)	2/4090 (0.05%)
Acute pulmonary oedema ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Atelectasis ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Bronchial hyperreactivity ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Haemothorax ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Nasal polyps ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Pneumonitis ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Respiratory acidosis ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Aspiration ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Bronchitis chronic ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Emphysema ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Haemoptysis ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Hiccups ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Lung disorder ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Pharyngeal mass ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Pneumomediastinum ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Rhinitis allergic ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Status asthmaticus ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Wheezing ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Bronchiectasis ^† 1	0/4089 (0.00%)	4/4090 (0.10%)
Bronchial fistula ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Bronchospasm ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Hypercapnia ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Nasal septum deviation ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Nasal turbinate hypertrophy ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Pulmonary mass ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Respiratory arrest ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Tracheal mass ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Skin and subcutaneous tissue disorders
Skin ulcer ^† 1	5/4089 (0.12%)	3/4090 (0.07%)
Diabetic foot ^† 1	2/4089 (0.05%)	2/4090 (0.05%)
Diabetic ulcer ^† 1	2/4089 (0.05%)	1/4090 (0.02%)
Angioedema ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Dermal cyst ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Ecchymosis ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Granuloma annulare ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Photosensitivity reaction ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Rash erythematous ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Hyperhidrosis ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Panniculitis ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Urticaria ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Surgical and medical procedures
Knee arthroplasty ^† 1	3/4089 (0.07%)	0/4090 (0.00%)
Implantable defibrillator insertion ^† 1	2/4089 (0.05%)	1/4090 (0.02%)
Lung lobectomy ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Aortic valve replacement ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Artificial urinary sphincter implant ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Hospitalisation ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Polypectomy ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Rotator cuff repair ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Shoulder operation ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Stem cell transplant ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Transurethral prostatectomy ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Cardiac ablation ^† 1	0/4089 (0.00%)	2/4090 (0.05%)
Spinal operation ^† 1	0/4089 (0.00%)	2/4090 (0.05%)
Endotracheal intubation ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Gastric bypass ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Hip arthroplasty ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Large intestinal polypectomy ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Transurethral bladder resection ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Vascular disorders
Hypertensive crisis ^† 1	15/4089 (0.37%)	11/4090 (0.27%)
Hypertension ^† 1	12/4089 (0.29%)	16/4090 (0.39%)
Hypotension ^† 1	9/4089 (0.22%)	11/4090 (0.27%)
Deep vein thrombosis ^† 1	5/4089 (0.12%)	8/4090 (0.20%)
Aortic stenosis ^† 1	4/4089 (0.10%)	10/4090 (0.24%)
Orthostatic hypotension ^† 1	4/4089 (0.10%)	5/4090 (0.12%)
Aortic aneurysm ^† 1	3/4089 (0.07%)	1/4090 (0.02%)
Peripheral arterial occlusive disease ^† 1	2/4089 (0.05%)	3/4090 (0.07%)
Hypovolaemic shock ^† 1	2/4089 (0.05%)	1/4090 (0.02%)
Accelerated hypertension ^† 1	2/4089 (0.05%)	0/4090 (0.00%)
Peripheral vascular disorder ^† 1	2/4089 (0.05%)	0/4090 (0.00%)
Shock haemorrhagic ^† 1	2/4089 (0.05%)	0/4090 (0.00%)
Peripheral ischaemia ^† 1	1/4089 (0.02%)	3/4090 (0.07%)
Peripheral artery occlusion ^† 1	1/4089 (0.02%)	2/4090 (0.05%)
Aortic aneurysm rupture ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Haematoma ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Hypertensive emergency ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Intermittent claudication ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Shock ^† 1	1/4089 (0.02%)	1/4090 (0.02%)
Angiodysplasia ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Arteriovenous fistula ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Circulatory collapse ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Embolism arterial ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Extravasation blood ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Iliac artery occlusion ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Jugular vein thrombosis ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Malignant hypertension ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Peripheral embolism ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Renovascular hypertension ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Thrombophlebitis superficial ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Vena cava thrombosis ^† 1	1/4089 (0.02%)	0/4090 (0.00%)
Blood pressure fluctuation ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Extremity necrosis ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Leriche syndrome ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Temporal arteritis ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Thrombophlebitis ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Thrombosis ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
Vasculitis ^† 1	0/4089 (0.00%)	1/4090 (0.02%)
1 Term from vocabulary, MedDRA Version 20.1 † Indicates events were collected by systematic assessment