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Clinical Trial Results:
PROSPECTIVE, RANDOMIZED TRIAL OF TICAGRELOR VERSUS PRASUGREL IN PATIENTS WITH ACUTE CORONARY SYNDROME Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment – ISAR-REACT 5

Summary
EudraCT number	2013-002272-40
Trial protocol	DE IT
Global end of trial date	20 Sep 2021

Results information
Results version number	v1(current)
This version publication date	15 Dec 2022
First version publication date	15 Dec 2022
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

GE-IDE-No.00113

ISRCTN number

US NCT number

NCT01944800

WHO universal trial number (UTN)

Sponsor organisation name

Deutsches Herzzentrum München, Klinik an der Technischen Universität München

Sponsor organisation address

Lazarettstr. 36, Munich, Germany, 80636

Public contact

ISAResearch Center, Deutsches Herzzentrum München, +49 8912184578, kastrati@dhm.mhn.de

Scientific contact

ISAResearch Center, Deutsches Herzzentrum München, +49 8912184578, kastrati@dhm.mhn.de

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

15 Sep 2022

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

20 Sep 2021

Was the trial ended prematurely?

Main objective of the trial

The objective of this study is to test the hypothesis that ticagrelor is superior to prasugrel regarding the composite of death, myocardial infarction or stroke at 12 months after randomisation.

Protection of trial subjects

Not applicable.

Background therapy

All patients will receive a loading dose of 150-500 mg of chewed or i.v. ASA (if they have not received it within the last 12 hours). Afterwards, all patients will receive an oral maintenance dose of 75-150 mg/day ASA for the duration of the study. Exploratory analyses of the PLATO trial suggest a possible association of ticagrelor with ASA dose such that reduced efficacy was observed with ticagrelor with increasing ASA doses. Therefore, the recommended chronic daily ASA dose to accompany ticagrelor is 75-150 mg. Other cardiac medications (e.g. ß-blockers, ACE-inhibitors, statins etc.) will be given according to the judgement of patient’s physician, current practice guidelines and the summary of medical product characteristics.

Evidence for comparator

Although both drugs provided superior efficacy compared to clopidogrel in the pivotal randomized trials, ACS patients continue to have an excess risk of ischemic events. Moreover, both drugs were shown to increase bleeding. Due to different ACS populations and conditions investigated the relative merits of prasugrel and ticagrelor in the treatment of ACS patients with planned invasive strategy cannot be reliably estimated from independent trials alone. To date, no direct head-to-head comparison of the two new P2Y12 receptor antagonists prasugrel and ticagrelor in terms of clinical outcome exists. The hypothesis to be tested will therefore be that ticagrelor is superior to prasugrel in terms of clinical outcomes. This will be achieved by means of a randomized, open label, multicentre trial. The primary endpoint will be the composite of death, myocardial infarction or stroke at 12 months after randomisation.

Actual start date of recruitment

01 Sep 2013

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Germany: 3328

Country: Number of subjects enrolled

Italy: 690

Worldwide total number of subjects

4018

EEA total number of subjects

4018

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

1968

From 65 to 84 years

1908

85 years and over

142

Subject disposition

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Recruitment details

The recruitment for the trial started in Sep 2013.

Screening details

For inclusion the patients had to fulfil the following criteria: 1. Hospitalization for an acute coronary syndrome (unstable angina pectoris, non-ST-segment elevation myocardial infarction, or ST-segment elevation myocardial infarction) with planned invasive strategy 2. age ≥18 years 3. Written informed consent

Period 1 title

Baseline

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Ticagrelor

Arm description

Arm type

Experimental

Investigational medicinal product name

Brilique

Investigational medicinal product code

Other name

Ticagrelor

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Both study medications, ticagrelor and prasugrel, are for oral use. They can be administered with or without food. Therapy with ticagrelor should be started with a loading dose of 180 mg (2 tablets of 90 mg) and continued with a maintenance dose of 90 mg twice daily. Maintenance doses should be taken in the morning and in the evening, at approximately 12-hour intervals.

Prasugrel

Arm description

Arm type

Active comparator

Investigational medicinal product name

Efient

Investigational medicinal product code

Other name

Prasugrel

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Both study medications, ticagrelor and prasugrel, are for oral use. They can be administered with or without food. Therapy with prasugrel should be started with a loading dose of 60 mg (6 tablets of 10 mg) and continued with a maintenance dose of 10 mg once per day. A reduced maintenance dose of 5 mg daily is recommended in patients at the age of 75 years or older or with a body weight of less than 60 kg.

Number of subjects in period 1	Ticagrelor	Prasugrel
Started	2012	2006
Completed	2012	2006

Period 2 title

1-year Follow-up

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Ticagrelor

Arm description

Arm type

Experimental

Investigational medicinal product name

Brilique

Investigational medicinal product code

Other name

Ticagrelor

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Prasugrel

Arm description

Arm type

Active comparator

Investigational medicinal product name

Efient

Investigational medicinal product code

Other name

Prasugrel

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Number of subjects in period 2	Ticagrelor	Prasugrel
Started	2012	2006
Completed	1971	1957
Not completed	41	49
Consent withdrawn by subject	22	31
Lost to follow-up	19	18

Period 3 title

3-year Follow-up

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Ticagrelor

Arm description

Arm type

Experimental

Investigational medicinal product name

Brilique

Investigational medicinal product code

Other name

Ticagrelor

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Prasugrel

Arm description

Arm type

Active comparator

Investigational medicinal product name

Efient

Investigational medicinal product code

Other name

Prasugrel

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Number of subjects in period 3	Ticagrelor	Prasugrel
Started	1971	1957
Completed	1921	1906
Not completed	50	51
Consent withdrawn by subject	3	1
Lost to follow-up	47	50

Baseline characteristics

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Reporting group title

Ticagrelor

Reporting group description

Reporting group title

Prasugrel

Reporting group description

Reporting group values	Ticagrelor	Prasugrel	Total
Number of subjects	2012	2006	4018
Age categorical
Units: Subjects
Adults (18-64 years)	976	992	1968
From 65-84 years	966	942	1908
85 years and over	70	72	142
Age continuous
Units: years
median (standard deviation)	64.5 ( 12.0 )	64.6 ( 12.1 )	-
Gender categorical
Units: Subjects
Female	478	478	956
Male	1534	1528	3062
Diabetes
Units: Subjects
Diabetes yes	463	429	892
Diabetes no	1548	1576	3124
Not recorded	1	1	2
Use of insulin for diabetes
Units: Subjects
Use of insulin for diabetes yes	143	137	280
se of insulin for diabetes no	1868	1868	3736
Not recorded	1	1	2
Current smoker
Units: Subjects
Current smoker yes	682	667	1349
Current smoker no	1320	1332	2652
Not recorded	10	7	17
Arterial hypertension
Units: Subjects
Arterial hypertension yes	1432	1384	2816
Arterial hypertension no	576	619	1195
Not recorded	4	3	7
Hypercholesterolemia
Units: Subjects
Hypercholesterolemia yes	1178	1163	2341
Hypercholesterianemia no	829	840	1669
Not recorded	5	3	8
Myocardial Infarction
Units: Subjects
Myocardial infarction yes	311	320	631
Myocardial infarction no	1699	1685	3384
Not recorded	2	1	3
PCI
Units: Subjects
PCI yes	453	463	916
PCI no	1558	1541	3099
Not recorded	1	2	3
Aortocoronary bypass surgery
Units: Subjects
Aortocoronary bypass surgery yes	115	130	245
Aortocoronary bypass surgery no	1896	1875	3771
Not recorded	1	1	2
Cardiogenic shock
Units: Subjects
Cardiogenic shock yes	31	34	65
Cardiogenic shock no	1981	1972	3953
Weight < 60 kg
Units: Subjects
Weight < 60 kg yes	108	94	202
Weight < 60 kg no	1895	1894	3789
Not recorded	9	18	27
Diagnosis at admission
Units: Subjects
Unstable angina	249	261	510
NSTEMI	930	925	1855
STEMI	833	820	1653
Coronary angiography
Units: Subjects
Coronary angiography yes	2003	2001	4004
Coronary angiography no	9	5	14
Treatment strategy
Units: Subjects
PCI	1676	1701	3377
CABG	47	36	83
Conservative therapy	285	268	553
Other	1	0	1
Not recorded	3	1	4
Blood pressure systolic
Units: mmHg
median (standard deviation)	144 ( 25 )	143 ( 24 )	-
Blood pressure diastolic
Units: mmHg
median (standard deviation)	82 ( 15 )	82 ( 14 )	-
Heart rate
Units: beats/min
median (standard deviation)	77 ( 16 )	76 ( 16 )	-
BMI
Units: kg/m2
median (standard deviation)	27.8 ( 4.6 )	27.8 ( 4.4 )	-
Creatinine level
Units: µmol/L
median (standard deviation)	88 ( 27 )	88 ( 31 )	-

End points

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Reporting group title

Ticagrelor

Reporting group description

Reporting group title

Prasugrel

Reporting group description

Reporting group title

Ticagrelor

Reporting group description

Reporting group title

Prasugrel

Reporting group description

Reporting group title

Ticagrelor

Reporting group description

Reporting group title

Prasugrel

Reporting group description

Primary: Composite of death, myocardial infarction, stroke

Top of page

End point title

Composite of death, myocardial infarction, stroke

End point description

End point type

Primary

End point timeframe

1 year after randomization

End point values	Ticagrelor	Prasugrel
Number of subjects analysed	2012	2006
Units: Patients	184	137

Endpoint analysis

Statistical analysis description

ITT

Comparison groups

Ticagrelor v Prasugrel

Number of subjects included in analysis

4018

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.05

Method

Regression, Cox

Parameter type

Hazard ratio (HR)

Point estimate

1.36

Confidence interval

level

95%

sides

2-sided

lower limit

1.09

upper limit

1.7

Secondary: Death

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End point title

Death

End point description

End point type

Secondary

End point timeframe

1 year after randomization

End point values	Ticagrelor	Prasugrel
Number of subjects analysed	2012	2006
Units: Events
From any cause	90	73

Endpoint analysis

Statistical analysis description

ITT

Comparison groups

Ticagrelor v Prasugrel

Number of subjects included in analysis

4018

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.05

Method

Regression, Cox

Parameter type

Hazard ratio (HR)

Point estimate

1.23

Confidence interval

level

95%

sides

2-sided

lower limit

0.91

upper limit

1.68

Secondary: Myocardial infarction

Top of page

End point title

Myocardial infarction

End point description

End point type

Secondary

End point timeframe

1 year after randomization

End point values	Ticagrelor	Prasugrel
Number of subjects analysed	2012	2006
Units: Events
Myocardial infarction	96	60

Endpoint analysis

Statistical analysis description

ITT

Comparison groups

Ticagrelor v Prasugrel

Number of subjects included in analysis

4018

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.05

Method

Regression, Cox

Parameter type

Hazard ratio (HR)

Point estimate

1.63

Confidence interval

level

95%

sides

2-sided

lower limit

1.18

upper limit

2.25

Secondary: Stroke

Top of page

End point title

Stroke

End point description

End point type

Secondary

End point timeframe

1 year after randomization

End point values	Ticagrelor	Prasugrel
Number of subjects analysed	2012	2006
Units: Subjects	22	19

Endpoint analysis

Statistical analysis description

ITT

Comparison groups

Ticagrelor v Prasugrel

Number of subjects included in analysis

4018

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.05

Method

Regression, Cox

Parameter type

Hazard ratio (HR)

Point estimate

1.17

Confidence interval

level

95%

sides

2-sided

lower limit

0.63

upper limit

2.15

Secondary: Definite or probable stent thrombosis

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End point title

Definite or probable stent thrombosis

End point description

End point type

Secondary

End point timeframe

1 year after randomization

End point values	Ticagrelor	Prasugrel
Number of subjects analysed	2012	2006
Units: Subjects	26	20

Endpoint analysis

Statistical analysis description

ITT

Comparison groups

Ticagrelor v Prasugrel

Number of subjects included in analysis

4018

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.05

Method

Regression, Cox

Parameter type

Hazard ratio (HR)

Point estimate

1.3

Confidence interval

level

95%

sides

2-sided

lower limit

0.72

upper limit

2.33

Secondary: Safety endpoint (Bleeding BARC type 3, 4 or 5)

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End point title

Safety endpoint (Bleeding BARC type 3, 4 or 5)

End point description

End point type

Secondary

End point timeframe

1 year after randomization

End point values	Ticagrelor	Prasugrel
Number of subjects analysed	1989	1773
Units: Subjects	95	80

Endpoint analysis

Statistical analysis description

modified ITT (all patients who received at least one dose of the randomly assigned trial drug and were assessed for bleeding events up to 7 days after discontinuation of the trial drug)

Comparison groups

Ticagrelor v Prasugrel

Number of subjects included in analysis

3762

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.05

Method

Regression, Cox

Parameter type

Hazard ratio (HR)

Point estimate

1.12

Confidence interval

level

95%

sides

2-sided

lower limit

0.83

upper limit

1.51

Adverse events

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Timeframe for reporting adverse events

During the one year follow-up period all SAEs were reported, after the one year follow-up period until the 3 year follow-up only fatal and lifethreatening events were reported.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

Reporting group title

Ticagrelor

Reporting group description

For SAE evaluation the ITT population was taken. In the Ticagrelor group 1180 non-serious adverse events occured. A detailed analysis of non-serious adverse events was not performed.

Reporting group title

Prasugrel

Reporting group description

For SAE evaluation the ITT population was taken. In the Prasugrel group 1102 non-serious adverse events occured. A detailed analysis of non-serious adverse events was not performed.

Notes
[1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported.
Justification: A detailed analysis of non-serious adverse events was not performed.

Serious adverse events	Ticagrelor	Prasugrel
Total subjects affected by serious adverse events
subjects affected / exposed	778 / 2012 (38.67%)	757 / 2006 (37.74%)
number of deaths (all causes)	147	136
number of deaths resulting from adverse events	147	136
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia
subjects affected / exposed	1 / 2012 (0.05%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Adenocarcinoma of colon
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Adenocarcinoma gastric
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Anal cancer
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Appendix cancer
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Basal cell carcinoma
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Bladder cancer
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Brain neoplasm
subjects affected / exposed	1 / 2012 (0.05%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 0
Breast cancer
subjects affected / exposed	2 / 2012 (0.10%)	3 / 2006 (0.15%)
occurrences causally related to treatment / all	0 / 2	0 / 3
deaths causally related to treatment / all	0 / 1	0 / 1
Bronchial carcinoma
subjects affected / exposed	3 / 2012 (0.15%)	2 / 2006 (0.10%)
occurrences causally related to treatment / all	0 / 3	0 / 2
deaths causally related to treatment / all	0 / 1	0 / 1
Cardiac myxoma
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cholangiocarcinoma
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Colon cancer
subjects affected / exposed	3 / 2012 (0.15%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 2	0 / 0
Colorectal cancer
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Endometrial cancer metastatic
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Extranodal marginal zone B-cell lymphoma (MALT type)
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Gastric cancer
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal carcinoma
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Glioblastoma
subjects affected / exposed	0 / 2012 (0.00%)	2 / 2006 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 1
Glioblastoma multiforme
subjects affected / exposed	4 / 2012 (0.20%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 4	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Intraductal papillary-mucinous carcinoma of pancreas
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Lung neoplasm malignant
subjects affected / exposed	6 / 2012 (0.30%)	3 / 2006 (0.15%)
occurrences causally related to treatment / all	0 / 6	0 / 3
deaths causally related to treatment / all	0 / 4	0 / 1
Lymphoma
subjects affected / exposed	1 / 2012 (0.05%)	2 / 2006 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 1	0 / 1
Malignant melanoma
subjects affected / exposed	1 / 2012 (0.05%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Non-small cell lung cancer
subjects affected / exposed	1 / 2012 (0.05%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 0
Oesophageal carcinoma
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pancreatic carcinoma
subjects affected / exposed	1 / 2012 (0.05%)	2 / 2006 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 1	0 / 1
Pancreatic carcinoma metastatic
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Plasma cell myeloma
subjects affected / exposed	1 / 2012 (0.05%)	3 / 2006 (0.15%)
occurrences causally related to treatment / all	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Prostate cancer
subjects affected / exposed	4 / 2012 (0.20%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 4	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 1
Rectal adenocarcinoma
subjects affected / exposed	3 / 2012 (0.15%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Rectal cancer
Additional description: Related event associated with bleeding
subjects affected / exposed	4 / 2012 (0.20%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	1 / 4	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Renal cancer recurrent
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Testis cancer
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Transitional cell carcinoma
subjects affected / exposed	1 / 2012 (0.05%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 0
Uterine leiomyoma
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
T-cell lymphoma
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Vascular disorders
Anaphylactic reaction
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Aortic aneurysm
subjects affected / exposed	2 / 2012 (0.10%)	2 / 2006 (0.10%)
occurrences causally related to treatment / all	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Aortic aneurysm rupture
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Aortic dissection
subjects affected / exposed	5 / 2012 (0.25%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 5	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Aortic occlusion
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Aortitis
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Arterial haemorrhage
subjects affected / exposed	1 / 2012 (0.05%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	1 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Arterial occlusive disease
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Artery dissection
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Circulatory collapse
subjects affected / exposed	3 / 2012 (0.15%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 3	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Coeliac artery occlusion
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Deep vein thrombosis
subjects affected / exposed	1 / 2012 (0.05%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Distributive shock
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Embolism
subjects affected / exposed	2 / 2012 (0.10%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Giant cell arteritis
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Haematoma
subjects affected / exposed	2 / 2012 (0.10%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	1 / 2	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Haemodynamic instability
subjects affected / exposed	1 / 2012 (0.05%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Haemorrhage
subjects affected / exposed	2 / 2012 (0.10%)	6 / 2006 (0.30%)
occurrences causally related to treatment / all	2 / 3	5 / 6
deaths causally related to treatment / all	0 / 0	0 / 0
Hypertension
subjects affected / exposed	9 / 2012 (0.45%)	10 / 2006 (0.50%)
occurrences causally related to treatment / all	0 / 11	0 / 10
deaths causally related to treatment / all	0 / 0	0 / 0
Hypertensive crisis
Additional description: Related event associated with bleeding
subjects affected / exposed	18 / 2012 (0.89%)	29 / 2006 (1.45%)
occurrences causally related to treatment / all	0 / 18	1 / 38
deaths causally related to treatment / all	0 / 0	0 / 0
Hypotension
subjects affected / exposed	6 / 2012 (0.30%)	2 / 2006 (0.10%)
occurrences causally related to treatment / all	0 / 6	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Intermittent claudication
subjects affected / exposed	0 / 2012 (0.00%)	4 / 2006 (0.20%)
occurrences causally related to treatment / all	0 / 0	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Leriche syndrome
subjects affected / exposed	1 / 2012 (0.05%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Lymphoedema
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Orthostatic hypotension
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Penetrating aortic ulcer
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Peripheral arterial occlusive disease
subjects affected / exposed	16 / 2012 (0.80%)	10 / 2006 (0.50%)
occurrences causally related to treatment / all	0 / 20	0 / 11
deaths causally related to treatment / all	0 / 0	0 / 1
Peripheral artery occlusion
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Peripheral artery restenosis
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Peripheral artery stenosis
subjects affected / exposed	4 / 2012 (0.20%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 4	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Peripheral ischaemia
subjects affected / exposed	2 / 2012 (0.10%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Shock
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Shock haemorrhagic
subjects affected / exposed	4 / 2012 (0.20%)	4 / 2006 (0.20%)
occurrences causally related to treatment / all	2 / 4	3 / 4
deaths causally related to treatment / all	1 / 2	1 / 1
Skin ulcer
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Subclavian artery stenosis
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Subgaleal haematoma
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Vascular graft stenosis
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Venous thrombosis limb
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Surgical and medical procedures
Alcohol detoxification
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Aortic valve replacement
subjects affected / exposed	1 / 2012 (0.05%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac pacemaker replacement
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Colectomy
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Coronary artery bypass
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Finger amputation
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hospitalisation
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Knee arthroplasty
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Limb operation
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Proctectomy
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
General disorders and administration site conditions
Adverse drug reaction
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Asthenia
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Chest pain
Additional description: Related due to dyspnoea
subjects affected / exposed	63 / 2012 (3.13%)	46 / 2006 (2.29%)
occurrences causally related to treatment / all	1 / 74	0 / 50
deaths causally related to treatment / all	0 / 0	0 / 0
Death
subjects affected / exposed	20 / 2012 (0.99%)	31 / 2006 (1.55%)
occurrences causally related to treatment / all	0 / 20	0 / 31
deaths causally related to treatment / all	0 / 20	0 / 31
Fatigue
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gait disturbance
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hernia incarcerated
subjects affected / exposed	0 / 2012 (0.00%)	2 / 2006 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Impaired healing
subjects affected / exposed	3 / 2012 (0.15%)	3 / 2006 (0.15%)
occurrences causally related to treatment / all	0 / 3	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Implant site haematoma
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Implant site haemorrhage
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Malaise
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Multiple organ dysfunction syndrome
subjects affected / exposed	4 / 2012 (0.20%)	5 / 2006 (0.25%)
occurrences causally related to treatment / all	0 / 4	0 / 5
deaths causally related to treatment / all	0 / 4	0 / 5
Pain
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Systemic inflammatory response syndrome
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Immune system disorders
Anaphylactic shock
subjects affected / exposed	2 / 2012 (0.10%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	1 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Dermatitis allergic
subjects affected / exposed	1 / 2012 (0.05%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Drug hypersensitivity
subjects affected / exposed	7 / 2012 (0.35%)	4 / 2006 (0.20%)
occurrences causally related to treatment / all	7 / 7	3 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Eosinophilic granulomatosis with polyangiitis
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Urticaria
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Reproductive system and breast disorders
Erectile dysfunction
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Heavy menstrual bleeding
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Vaginal haemorrhage
subjects affected / exposed	2 / 2012 (0.10%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	1 / 2	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Acute respiratory distress syndrome
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Acute respiratory failure
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Asthma
subjects affected / exposed	0 / 2012 (0.00%)	2 / 2006 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Chronic obstructive airways disease exacerbated
subjects affected / exposed	2 / 2012 (0.10%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Chronic obstructive pulmonary disease
subjects affected / exposed	9 / 2012 (0.45%)	2 / 2006 (0.10%)
occurrences causally related to treatment / all	0 / 11	0 / 8
deaths causally related to treatment / all	0 / 2	0 / 0
Dyspnoea
subjects affected / exposed	23 / 2012 (1.14%)	16 / 2006 (0.80%)
occurrences causally related to treatment / all	9 / 24	0 / 16
deaths causally related to treatment / all	0 / 0	0 / 0
Emphysema
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Epistaxis
subjects affected / exposed	3 / 2012 (0.15%)	3 / 2006 (0.15%)
occurrences causally related to treatment / all	2 / 3	2 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Haemoptysis
subjects affected / exposed	2 / 2012 (0.10%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	2 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Haemothorax
subjects affected / exposed	1 / 2012 (0.05%)	4 / 2006 (0.20%)
occurrences causally related to treatment / all	1 / 1	1 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Nasal septum deviation
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pleural effusion
subjects affected / exposed	3 / 2012 (0.15%)	3 / 2006 (0.15%)
occurrences causally related to treatment / all	0 / 3	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Pleural mass
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pleurisy
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia aspiration
subjects affected / exposed	4 / 2012 (0.20%)	4 / 2006 (0.20%)
occurrences causally related to treatment / all	0 / 4	0 / 4
deaths causally related to treatment / all	0 / 1	0 / 2
Pneumothorax
subjects affected / exposed	1 / 2012 (0.05%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumothorax spontaneous
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pulmonary embolism
subjects affected / exposed	11 / 2012 (0.55%)	8 / 2006 (0.40%)
occurrences causally related to treatment / all	0 / 11	0 / 8
deaths causally related to treatment / all	0 / 0	0 / 1
Pulmonary fibrosis
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pulmonary haemorrhage
subjects affected / exposed	0 / 2012 (0.00%)	2 / 2006 (0.10%)
occurrences causally related to treatment / all	0 / 0	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Pulmonary hypertension
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pulmonary oedema
subjects affected / exposed	19 / 2012 (0.94%)	13 / 2006 (0.65%)
occurrences causally related to treatment / all	0 / 20	0 / 13
deaths causally related to treatment / all	0 / 1	0 / 1
Respiratory distress
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory failure
subjects affected / exposed	1 / 2012 (0.05%)	3 / 2006 (0.15%)
occurrences causally related to treatment / all	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 1
Sleep apnoea syndrome
subjects affected / exposed	1 / 2012 (0.05%)	2 / 2006 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Tachypnoea
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Thoracic haemorrhage
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Tracheobronchopathia osteoplastica
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Vocal cord thickening
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Psychiatric disorders
Agitation
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Anxiety
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Delirium
subjects affected / exposed	2 / 2012 (0.10%)	4 / 2006 (0.20%)
occurrences causally related to treatment / all	0 / 2	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Depression
subjects affected / exposed	1 / 2012 (0.05%)	4 / 2006 (0.20%)
occurrences causally related to treatment / all	0 / 1	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Panic attack
subjects affected / exposed	2 / 2012 (0.10%)	2 / 2006 (0.10%)
occurrences causally related to treatment / all	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Psychotic disorder
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Somatic symptom disorder
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Substance-induced psychotic disorder
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Suicide attempt
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Product issues
Device capturing issue
subjects affected / exposed	0 / 2012 (0.00%)	2 / 2006 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Device failure
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Device malfunction
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Prosthetic cardiac valve malfunction
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatobiliary disorders
Autoimmune hepatitis
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cholangitis
subjects affected / exposed	0 / 2012 (0.00%)	2 / 2006 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Cholecystitis acute
subjects affected / exposed	2 / 2012 (0.10%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Cholelithiasis
subjects affected / exposed	2 / 2012 (0.10%)	4 / 2006 (0.20%)
occurrences causally related to treatment / all	0 / 2	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatic cyst ruptured
Additional description: Associated with bleeding
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatic failure
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatic haematoma
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatitis
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac cirrhosis
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Cholecystitis
subjects affected / exposed	5 / 2012 (0.25%)	2 / 2006 (0.10%)
occurrences causally related to treatment / all	0 / 5	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Investigations
Arteriogram coronary normal
subjects affected / exposed	1 / 2012 (0.05%)	2 / 2006 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Blood creatine increased
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Blood electrolytes decreased
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Blood glucose abnormal
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Ejection fraction decreased
subjects affected / exposed	1 / 2012 (0.05%)	2 / 2006 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Electrocardiogram abnormal
subjects affected / exposed	2 / 2012 (0.10%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Haemoglobin decreased
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
International normalised ratio increased
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Investigation abnormal
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Myocardial necrosis marker increased
subjects affected / exposed	5 / 2012 (0.25%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 5	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Stress echocardiogram abnormal
subjects affected / exposed	0 / 2012 (0.00%)	2 / 2006 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Transaminases increased
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Troponin increased
subjects affected / exposed	1 / 2012 (0.05%)	2 / 2006 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Weight decreased
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Injury, poisoning and procedural complications
Abdominal wound dehiscence
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Anaemia postoperative
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Concussion
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Delayed recovery from anaesthesia
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Facial bones fracture
subjects affected / exposed	1 / 2012 (0.05%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Fall
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Femoral neck fracture
subjects affected / exposed	2 / 2012 (0.10%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Foot fracture
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Heat stroke
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Implant site infection
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Intraoperative haemorrhage
Additional description: Intraoperative haemorrhage
subjects affected / exposed	4 / 2012 (0.20%)	3 / 2006 (0.15%)
occurrences causally related to treatment / all	4 / 4	2 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Limb fracture
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Lumbar vertebral fracture
subjects affected / exposed	0 / 2012 (0.00%)	2 / 2006 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Multiple fractures
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pelvic fracture
subjects affected / exposed	0 / 2012 (0.00%)	2 / 2006 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Periprocedural myocardial infarction
subjects affected / exposed	6 / 2012 (0.30%)	3 / 2006 (0.15%)
occurrences causally related to treatment / all	0 / 6	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumothorax traumatic
subjects affected / exposed	1 / 2012 (0.05%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 0
Post procedural complication
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Post procedural haematoma
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Post procedural haemorrhage
subjects affected / exposed	2 / 2012 (0.10%)	4 / 2006 (0.20%)
occurrences causally related to treatment / all	1 / 2	3 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Post procedural myocardial infarction
subjects affected / exposed	4 / 2012 (0.20%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 4	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 0
Postoperative renal failure
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Postoperative wound complication
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Procedural complication
subjects affected / exposed	0 / 2012 (0.00%)	2 / 2006 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Procedural haemorrhage
subjects affected / exposed	2 / 2012 (0.10%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Rib fracture
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Skull fractured base
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Splenic rupture
Additional description: Associated with bleeding
subjects affected / exposed	2 / 2012 (0.10%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Shunt stenosis
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Subarachnoid haemorrhage
subjects affected / exposed	1 / 2012 (0.05%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	1 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	1 / 1
Subdural haematoma
subjects affected / exposed	3 / 2012 (0.15%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	2 / 4	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Tendon rupture
subjects affected / exposed	0 / 2012 (0.00%)	3 / 2006 (0.15%)
occurrences causally related to treatment / all	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Toxicity to various agents
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Tracheal haemorrhage
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Transfusion reaction
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Traumatic haemorrhage
subjects affected / exposed	2 / 2012 (0.10%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Traumatic haemothorax
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Vascular access site haematoma
subjects affected / exposed	9 / 2012 (0.45%)	4 / 2006 (0.20%)
occurrences causally related to treatment / all	8 / 9	3 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Vascular access site haemorrhage
subjects affected / exposed	7 / 2012 (0.35%)	7 / 2006 (0.35%)
occurrences causally related to treatment / all	7 / 7	7 / 7
deaths causally related to treatment / all	0 / 0	0 / 0
Vascular pseudoaneurysm
subjects affected / exposed	4 / 2012 (0.20%)	4 / 2006 (0.20%)
occurrences causally related to treatment / all	1 / 4	2 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Ventricle rupture
subjects affected / exposed	1 / 2012 (0.05%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Wound haemorrhage
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Congenital, familial and genetic disorders
Atrial septal defect
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac disorders
Acute coronary syndrome
subjects affected / exposed	3 / 2012 (0.15%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 3	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Acute myocardial infarction
subjects affected / exposed	67 / 2012 (3.33%)	45 / 2006 (2.24%)
occurrences causally related to treatment / all	0 / 72	0 / 49
deaths causally related to treatment / all	0 / 2	0 / 3
Angina pectoris
subjects affected / exposed	60 / 2012 (2.98%)	76 / 2006 (3.79%)
occurrences causally related to treatment / all	0 / 70	0 / 81
deaths causally related to treatment / all	0 / 0	0 / 0
Angina unstable
subjects affected / exposed	61 / 2012 (3.03%)	50 / 2006 (2.49%)
occurrences causally related to treatment / all	0 / 68	0 / 56
deaths causally related to treatment / all	0 / 0	0 / 0
Aortic valve stenosis
subjects affected / exposed	2 / 2012 (0.10%)	11 / 2006 (0.55%)
occurrences causally related to treatment / all	0 / 2	0 / 12
deaths causally related to treatment / all	0 / 0	0 / 1
Arrhythmia
subjects affected / exposed	5 / 2012 (0.25%)	3 / 2006 (0.15%)
occurrences causally related to treatment / all	0 / 5	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 1
Arteriospasm coronary
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Arteriosclerosis coronary artery
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Atrial fibrillation
subjects affected / exposed	31 / 2012 (1.54%)	30 / 2006 (1.50%)
occurrences causally related to treatment / all	0 / 36	0 / 32
deaths causally related to treatment / all	0 / 0	0 / 0
Atrial flutter
subjects affected / exposed	5 / 2012 (0.25%)	2 / 2006 (0.10%)
occurrences causally related to treatment / all	0 / 8	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Atrial tachycardia
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Atrial thrombosis
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Atrioventricular block
subjects affected / exposed	0 / 2012 (0.00%)	3 / 2006 (0.15%)
occurrences causally related to treatment / all	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Atrioventricular block complete
subjects affected / exposed	17 / 2012 (0.84%)	6 / 2006 (0.30%)
occurrences causally related to treatment / all	3 / 17	0 / 6
deaths causally related to treatment / all	0 / 0	0 / 0
Atrioventricular block first degree
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Atrioventricular block second degree
subjects affected / exposed	1 / 2012 (0.05%)	6 / 2006 (0.30%)
occurrences causally related to treatment / all	1 / 1	0 / 6
deaths causally related to treatment / all	0 / 0	0 / 0
Atrioventricular block third degree
subjects affected / exposed	3 / 2012 (0.15%)	3 / 2006 (0.15%)
occurrences causally related to treatment / all	1 / 3	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Bradyarrhythmia
subjects affected / exposed	0 / 2012 (0.00%)	2 / 2006 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Bradycardia
subjects affected / exposed	6 / 2012 (0.30%)	7 / 2006 (0.35%)
occurrences causally related to treatment / all	5 / 6	0 / 7
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac aneurysm
subjects affected / exposed	3 / 2012 (0.15%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 3	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac arrest
Additional description: Related event due to bradycardia
subjects affected / exposed	6 / 2012 (0.30%)	10 / 2006 (0.50%)
occurrences causally related to treatment / all	1 / 6	0 / 11
deaths causally related to treatment / all	0 / 1	0 / 0
Cardiac death
subjects affected / exposed	4 / 2012 (0.20%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 4	0 / 1
deaths causally related to treatment / all	0 / 4	0 / 1
Cardiac failure
subjects affected / exposed	38 / 2012 (1.89%)	34 / 2006 (1.69%)
occurrences causally related to treatment / all	0 / 41	0 / 49
deaths causally related to treatment / all	0 / 9	0 / 7
Cardiac failure acute
subjects affected / exposed	7 / 2012 (0.35%)	5 / 2006 (0.25%)
occurrences causally related to treatment / all	0 / 7	0 / 5
deaths causally related to treatment / all	0 / 2	0 / 3
Cardiac failure congestive
subjects affected / exposed	4 / 2012 (0.20%)	5 / 2006 (0.25%)
occurrences causally related to treatment / all	0 / 4	0 / 6
deaths causally related to treatment / all	0 / 3	0 / 3
Cardiac tamponade
subjects affected / exposed	2 / 2012 (0.10%)	2 / 2006 (0.10%)
occurrences causally related to treatment / all	1 / 2	1 / 2
deaths causally related to treatment / all	0 / 0	1 / 1
Cardiogenic shock
subjects affected / exposed	20 / 2012 (0.99%)	19 / 2006 (0.95%)
occurrences causally related to treatment / all	0 / 20	0 / 20
deaths causally related to treatment / all	0 / 12	0 / 12
Cardiomyopathy
subjects affected / exposed	1 / 2012 (0.05%)	3 / 2006 (0.15%)
occurrences causally related to treatment / all	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 1
Cardiopulmonary failure
subjects affected / exposed	0 / 2012 (0.00%)	3 / 2006 (0.15%)
occurrences causally related to treatment / all	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 2
Cardiorenal syndrome
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Cardiovascular insufficiency
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Coronary artery disease
subjects affected / exposed	32 / 2012 (1.59%)	21 / 2006 (1.05%)
occurrences causally related to treatment / all	0 / 32	0 / 23
deaths causally related to treatment / all	0 / 0	0 / 0
Coronary artery dissection
subjects affected / exposed	4 / 2012 (0.20%)	4 / 2006 (0.20%)
occurrences causally related to treatment / all	0 / 4	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 1
Coronary artery occlusion
subjects affected / exposed	2 / 2012 (0.10%)	4 / 2006 (0.20%)
occurrences causally related to treatment / all	0 / 2	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Coronary artery perforation
subjects affected / exposed	1 / 2012 (0.05%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Coronary artery restenosis
subjects affected / exposed	19 / 2012 (0.94%)	24 / 2006 (1.20%)
occurrences causally related to treatment / all	0 / 20	0 / 24
deaths causally related to treatment / all	0 / 0	0 / 0
Coronary artery stenosis
subjects affected / exposed	42 / 2012 (2.09%)	57 / 2006 (2.84%)
occurrences causally related to treatment / all	0 / 43	0 / 58
deaths causally related to treatment / all	0 / 0	0 / 0
Dressler's syndrome
subjects affected / exposed	2 / 2012 (0.10%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hypertrophic cardiomyopathy
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Interventricular septum rupture
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Intracardiac thrombus
subjects affected / exposed	5 / 2012 (0.25%)	4 / 2006 (0.20%)
occurrences causally related to treatment / all	0 / 5	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Ischaemic cardiomyopathy
subjects affected / exposed	5 / 2012 (0.25%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 5	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Left ventricular failure
subjects affected / exposed	2 / 2012 (0.10%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Mitral valve incompetence
subjects affected / exposed	4 / 2012 (0.20%)	8 / 2006 (0.40%)
occurrences causally related to treatment / all	0 / 4	0 / 8
deaths causally related to treatment / all	0 / 0	0 / 0
Myocardial infarction
subjects affected / exposed	19 / 2012 (0.94%)	17 / 2006 (0.85%)
occurrences causally related to treatment / all	0 / 19	0 / 18
deaths causally related to treatment / all	0 / 7	0 / 3
Myocardial ischaemia
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Myocardial rupture
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Myopericarditis
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Nodal arrhythmia
subjects affected / exposed	2 / 2012 (0.10%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Nodal rhythm
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Palpitations
subjects affected / exposed	2 / 2012 (0.10%)	2 / 2006 (0.10%)
occurrences causally related to treatment / all	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Pericardial effusion
subjects affected / exposed	1 / 2012 (0.05%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pericardial haemorrhage
subjects affected / exposed	7 / 2012 (0.35%)	4 / 2006 (0.20%)
occurrences causally related to treatment / all	6 / 7	2 / 5
deaths causally related to treatment / all	0 / 0	0 / 0
Pericarditis
subjects affected / exposed	2 / 2012 (0.10%)	3 / 2006 (0.15%)
occurrences causally related to treatment / all	0 / 3	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Pleuropericarditis
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Postinfarction angina
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Prinzmetal angina
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pulseless electrical activity
subjects affected / exposed	4 / 2012 (0.20%)	2 / 2006 (0.10%)
occurrences causally related to treatment / all	0 / 4	0 / 2
deaths causally related to treatment / all	0 / 2	0 / 1
Rhythm idioventricular
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Right heart failure
subjects affected / exposed	2 / 2012 (0.10%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 2	0 / 1
Right ventricular failure
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Sinus node dysfunction
subjects affected / exposed	3 / 2012 (0.15%)	3 / 2006 (0.15%)
occurrences causally related to treatment / all	0 / 3	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Sinuatrial block
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Sinus arrhythmia
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Sudden cardiac death
subjects affected / exposed	4 / 2012 (0.20%)	5 / 2006 (0.25%)
occurrences causally related to treatment / all	0 / 4	0 / 5
deaths causally related to treatment / all	0 / 4	0 / 5
Supraventricular tachycardia
subjects affected / exposed	3 / 2012 (0.15%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Syncope
subjects affected / exposed	1 / 2012 (0.05%)	2 / 2006 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Tachyarrhythmia
subjects affected / exposed	2 / 2012 (0.10%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Tachycardia
subjects affected / exposed	2 / 2012 (0.10%)	4 / 2006 (0.20%)
occurrences causally related to treatment / all	0 / 2	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Thrombosis in device
subjects affected / exposed	16 / 2012 (0.80%)	9 / 2006 (0.45%)
occurrences causally related to treatment / all	0 / 16	0 / 9
deaths causally related to treatment / all	0 / 3	0 / 1
Torsade de pointes
subjects affected / exposed	1 / 2012 (0.05%)	2 / 2006 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Ventricular arrhythmia
subjects affected / exposed	2 / 2012 (0.10%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Ventricular bigeminy
subjects affected / exposed	0 / 2012 (0.00%)	2 / 2006 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Ventricular dysfunction
subjects affected / exposed	1 / 2012 (0.05%)	2 / 2006 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Ventricular extrasystoles
subjects affected / exposed	2 / 2012 (0.10%)	4 / 2006 (0.20%)
occurrences causally related to treatment / all	0 / 2	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Ventricular fibrillation
subjects affected / exposed	21 / 2012 (1.04%)	17 / 2006 (0.85%)
occurrences causally related to treatment / all	0 / 21	0 / 18
deaths causally related to treatment / all	0 / 2	0 / 2
Ventricular flutter
subjects affected / exposed	1 / 2012 (0.05%)	2 / 2006 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Ventricular tachycardia
subjects affected / exposed	20 / 2012 (0.99%)	14 / 2006 (0.70%)
occurrences causally related to treatment / all	0 / 24	0 / 15
deaths causally related to treatment / all	0 / 0	0 / 1
Bundle branch block left
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Sick node dysfunction
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Nervous system disorders
Basal ganglia haemorrhage
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Brain hypoxia
subjects affected / exposed	1 / 2012 (0.05%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 1
Brain injury
subjects affected / exposed	7 / 2012 (0.35%)	5 / 2006 (0.25%)
occurrences causally related to treatment / all	0 / 7	0 / 5
deaths causally related to treatment / all	0 / 2	0 / 3
Brain stem ischaemia
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Carotid artery stenosis
subjects affected / exposed	3 / 2012 (0.15%)	2 / 2006 (0.10%)
occurrences causally related to treatment / all	0 / 3	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Cerebral haematoma
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Cerebral haemorrhage
subjects affected / exposed	5 / 2012 (0.25%)	3 / 2006 (0.15%)
occurrences causally related to treatment / all	1 / 5	1 / 3
deaths causally related to treatment / all	1 / 4	1 / 1
Cerebral ischaemia
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Cerebrovascular accident
subjects affected / exposed	18 / 2012 (0.89%)	22 / 2006 (1.10%)
occurrences causally related to treatment / all	0 / 20	0 / 22
deaths causally related to treatment / all	0 / 3	0 / 2
Cervical radiculopathy
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Dementia
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Dizziness
subjects affected / exposed	3 / 2012 (0.15%)	3 / 2006 (0.15%)
occurrences causally related to treatment / all	1 / 3	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Embolic stroke
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Epilepsy
subjects affected / exposed	0 / 2012 (0.00%)	3 / 2006 (0.15%)
occurrences causally related to treatment / all	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Facial paresis
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Global amnesia
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Intensive care unit acquired weakness
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Intercostal neuralgia
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Ischaemic stroke
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Neurodegenerative disorder
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Neurosarcoidosis
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Normal pressure hydrocephalus
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Paraesthesia
subjects affected / exposed	2 / 2012 (0.10%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Parkinsonism
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Presyncope
subjects affected / exposed	3 / 2012 (0.15%)	2 / 2006 (0.10%)
occurrences causally related to treatment / all	0 / 3	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Sciatica
subjects affected / exposed	0 / 2012 (0.00%)	2 / 2006 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Seizure
subjects affected / exposed	1 / 2012 (0.05%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Syncope
subjects affected / exposed	16 / 2012 (0.80%)	5 / 2006 (0.25%)
occurrences causally related to treatment / all	1 / 16	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0
Transient ischaemic attack
subjects affected / exposed	7 / 2012 (0.35%)	5 / 2006 (0.25%)
occurrences causally related to treatment / all	0 / 7	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0
Vasovagal attack
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	5 / 2012 (0.25%)	7 / 2006 (0.35%)
occurrences causally related to treatment / all	3 / 5	3 / 8
deaths causally related to treatment / all	0 / 0	0 / 0
Anaemia macrocytic
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Blood loss anaemia
subjects affected / exposed	2 / 2012 (0.10%)	8 / 2006 (0.40%)
occurrences causally related to treatment / all	2 / 2	5 / 8
deaths causally related to treatment / all	0 / 0	0 / 0
Coagulopathy
subjects affected / exposed	1 / 2012 (0.05%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Disseminated intravascular coagulation
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Febrile neutropenia
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Haemorrhagic diathesis
subjects affected / exposed	0 / 2012 (0.00%)	2 / 2006 (0.10%)
occurrences causally related to treatment / all	0 / 0	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Hyperleukocytosis
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Iron deficiency anaemia
subjects affected / exposed	2 / 2012 (0.10%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Normochromic normocytic anaemia
subjects affected / exposed	2 / 2012 (0.10%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	1 / 2	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Polycythaemia
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Thrombocytopenia
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Microcytic anaemia
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Ear and labyrinth disorders
Vertigo
subjects affected / exposed	3 / 2012 (0.15%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Vertigo positional
subjects affected / exposed	0 / 2012 (0.00%)	2 / 2006 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
VIIIth cranial nerve disorders
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Sudden hearing loss
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Eye disorders
Maculopathy
Additional description: Due to bleeding
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Optic ischaemic neuropathy
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Visual impairment
subjects affected / exposed	1 / 2012 (0.05%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Vitreous haemorrhage
subjects affected / exposed	0 / 2012 (0.00%)	2 / 2006 (0.10%)
occurrences causally related to treatment / all	0 / 0	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal compartment syndrome
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Abdominal pain
subjects affected / exposed	2 / 2012 (0.10%)	8 / 2006 (0.40%)
occurrences causally related to treatment / all	0 / 2	1 / 8
deaths causally related to treatment / all	0 / 0	0 / 0
Anal fistula
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Acute abdomen
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Anal haemorrhage
subjects affected / exposed	1 / 2012 (0.05%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	1 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Colitis
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Colitis ischaemic
subjects affected / exposed	2 / 2012 (0.10%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Colitis ulcerative
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Constipation
subjects affected / exposed	0 / 2012 (0.00%)	2 / 2006 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Diarrhoea
subjects affected / exposed	3 / 2012 (0.15%)	5 / 2006 (0.25%)
occurrences causally related to treatment / all	1 / 3	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0
Diverticulum intestinal haemorrhagic
subjects affected / exposed	3 / 2012 (0.15%)	2 / 2006 (0.10%)
occurrences causally related to treatment / all	2 / 3	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Duodenal ulcer
Additional description: Associated with bleeding
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Duodenal ulcer haemorrhage
subjects affected / exposed	1 / 2012 (0.05%)	2 / 2006 (0.10%)
occurrences causally related to treatment / all	1 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Duodenitis
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Dysphagia
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Enterocolitis
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Faecaloma
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastric haemorrhage
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastric cancer
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Gastric ulcer
subjects affected / exposed	3 / 2012 (0.15%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	2 / 4	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastritis
subjects affected / exposed	2 / 2012 (0.10%)	3 / 2006 (0.15%)
occurrences causally related to treatment / all	0 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Gastritis erosive
subjects affected / exposed	1 / 2012 (0.05%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastritis haemorrhagic
subjects affected / exposed	0 / 2012 (0.00%)	2 / 2006 (0.10%)
occurrences causally related to treatment / all	0 / 0	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	3 / 2012 (0.15%)	2 / 2006 (0.10%)
occurrences causally related to treatment / all	0 / 3	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal angiodysplasia
subjects affected / exposed	1 / 2012 (0.05%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	1 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal haemorrhage
subjects affected / exposed	20 / 2012 (0.99%)	19 / 2006 (0.95%)
occurrences causally related to treatment / all	18 / 20	14 / 19
deaths causally related to treatment / all	1 / 1	0 / 0
Gastrointestinal infection
subjects affected / exposed	1 / 2012 (0.05%)	2 / 2006 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal ischaemia
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal toxicity
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal necrosis
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal vascular malformation haemorrhagic
subjects affected / exposed	2 / 2012 (0.10%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	2 / 4	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrooesophageal reflux disease
subjects affected / exposed	2 / 2012 (0.10%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Haematemesis
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	1 / 1
Haemorrhoidal haemorrhage
subjects affected / exposed	0 / 2012 (0.00%)	2 / 2006 (0.10%)
occurrences causally related to treatment / all	0 / 0	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Heyde's syndrome
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Helicobacter gastritis
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hiatus hernia
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Ileus
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Ileus paralytic
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Intestinal ischaemia
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Inguinal hernia
subjects affected / exposed	2 / 2012 (0.10%)	2 / 2006 (0.10%)
occurrences causally related to treatment / all	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Lower gastrointestinal haemorrhage
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Mechanical ileus
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Mallory-Weiss syndrome
subjects affected / exposed	2 / 2012 (0.10%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Melaena
subjects affected / exposed	0 / 2012 (0.00%)	2 / 2006 (0.10%)
occurrences causally related to treatment / all	0 / 0	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Mesenteric vascular occlusion
subjects affected / exposed	1 / 2012 (0.05%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 0
Nausea
subjects affected / exposed	1 / 2012 (0.05%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Obstructive pancreatitis
subjects affected / exposed	1 / 2012 (0.05%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pancreatitis
subjects affected / exposed	1 / 2012 (0.05%)	2 / 2006 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Rectal haemorrhage
subjects affected / exposed	1 / 2012 (0.05%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Rectal perforation
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Retroperitoneal haematoma
subjects affected / exposed	2 / 2012 (0.10%)	2 / 2006 (0.10%)
occurrences causally related to treatment / all	2 / 2	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Retroperitoneal haemorrhage
subjects affected / exposed	1 / 2012 (0.05%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	1 / 1	1 / 1
deaths causally related to treatment / all	1 / 1	0 / 0
Subileus
subjects affected / exposed	0 / 2012 (0.00%)	2 / 2006 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Upper gastrointestinal haemorrhage
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Angioedema
subjects affected / exposed	1 / 2012 (0.05%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Decubitus ulcer
subjects affected / exposed	1 / 2012 (0.05%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Diabetic ulcer
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Prurigo
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Rash
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Skin ulcer
subjects affected / exposed	2 / 2012 (0.10%)	4 / 2006 (0.20%)
occurrences causally related to treatment / all	0 / 2	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	11 / 2012 (0.55%)	7 / 2006 (0.35%)
occurrences causally related to treatment / all	0 / 11	0 / 7
deaths causally related to treatment / all	0 / 0	0 / 0
Acute prerenal failure
subjects affected / exposed	3 / 2012 (0.15%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 3	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Acute renal injury
subjects affected / exposed	15 / 2012 (0.75%)	13 / 2006 (0.65%)
occurrences causally related to treatment / all	0 / 16	0 / 13
deaths causally related to treatment / all	0 / 1	0 / 0
Chronic kidney disease
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Cystitis haemorrhagic
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Haematuria
subjects affected / exposed	2 / 2012 (0.10%)	6 / 2006 (0.30%)
occurrences causally related to treatment / all	1 / 2	5 / 7
deaths causally related to treatment / all	0 / 0	0 / 0
Hydronephrosis
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Micturition disorder
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Oliguria
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Renal colic
subjects affected / exposed	1 / 2012 (0.05%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Renal cyst
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Renal failure
subjects affected / exposed	10 / 2012 (0.50%)	5 / 2006 (0.25%)
occurrences causally related to treatment / all	1 / 10	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0
Renal infarct
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Tubulointerstitial nephritis
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Ureterolithiasis
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Urethral haemorrhage
subjects affected / exposed	0 / 2012 (0.00%)	2 / 2006 (0.10%)
occurrences causally related to treatment / all	0 / 0	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Urinary retention
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Urogenital haemorrhage
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Endocrine disorders
Goitre
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hyperthyroidism
subjects affected / exposed	0 / 2012 (0.00%)	2 / 2006 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Thyrotoxic crisis
subjects affected / exposed	1 / 2012 (0.05%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	1 / 2012 (0.05%)	2 / 2006 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Antisynthetase syndrome
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Back pain
subjects affected / exposed	1 / 2012 (0.05%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Bursitis
subjects affected / exposed	1 / 2012 (0.05%)	2 / 2006 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Compartment syndrome
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Haemarthrosis
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Haematoma muscle
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Intervertebral disc protrusion
subjects affected / exposed	2 / 2012 (0.10%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Joint effusion
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Lumbar spinal stenosis
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Muscle haemorrhage
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Osteoarthritis
subjects affected / exposed	2 / 2012 (0.10%)	2 / 2006 (0.10%)
occurrences causally related to treatment / all	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Osteolysis
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Osteoporotic fracture
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pain in extremity
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pathological fracture
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Polymyalgia rheumatica
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Rhabdomyolysis
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Rheumatoid arthritis
subjects affected / exposed	1 / 2012 (0.05%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Sacral pain
subjects affected / exposed	0 / 2012 (0.00%)	2 / 2006 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Spinal osteoarthritis
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Infections and infestations
Abscess intestinal
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Abscess limb
subjects affected / exposed	2 / 2012 (0.10%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Abscess oral
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Appendicitis
subjects affected / exposed	3 / 2012 (0.15%)	3 / 2006 (0.15%)
occurrences causally related to treatment / all	0 / 3	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Atypical pneumonia
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Bacteriuria
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Bronchitis
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Clostridium difficile colitis
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Colon gangrene
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Cystitis
subjects affected / exposed	1 / 2012 (0.05%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Diverticulitis
subjects affected / exposed	0 / 2012 (0.00%)	6 / 2006 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 6
deaths causally related to treatment / all	0 / 0	0 / 0
Diverticulitis intestinal perforated
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Endocarditis
subjects affected / exposed	0 / 2012 (0.00%)	2 / 2006 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Enterococcal infection
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Epididymitis
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Erysipelas
subjects affected / exposed	1 / 2012 (0.05%)	3 / 2006 (0.15%)
occurrences causally related to treatment / all	0 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Escherichia sepsis
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Gastroenteritis clostridial
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gallbladder empyema
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gangrene
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Haematoma infection
subjects affected / exposed	2 / 2012 (0.10%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Infected lymphocele
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Infected skin ulcer
subjects affected / exposed	0 / 2012 (0.00%)	2 / 2006 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Infection
subjects affected / exposed	1 / 2012 (0.05%)	5 / 2006 (0.25%)
occurrences causally related to treatment / all	0 / 1	0 / 6
deaths causally related to treatment / all	0 / 0	0 / 0
Influenza
subjects affected / exposed	2 / 2012 (0.10%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Intervertebral discitis
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Medical device site infection
subjects affected / exposed	0 / 2012 (0.00%)	2 / 2006 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Meningitis
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Nasopharyngitis
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Neutropenic sepsis
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Orchitis
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Peritoneal abscess
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Peritonitis
subjects affected / exposed	2 / 2012 (0.10%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pleural infection
subjects affected / exposed	2 / 2012 (0.10%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	69 / 2012 (3.43%)	47 / 2006 (2.34%)
occurrences causally related to treatment / all	0 / 73	0 / 50
deaths causally related to treatment / all	0 / 10	0 / 3
Pulmonary sepsis
subjects affected / exposed	1 / 2012 (0.05%)	2 / 2006 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 1
Post procedural pneumonia
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pseudoaneurysm infection
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pyelonephritis
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Respiratory tract infection
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Retroperitoneal abscess
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Sepsis
subjects affected / exposed	9 / 2012 (0.45%)	7 / 2006 (0.35%)
occurrences causally related to treatment / all	0 / 9	0 / 7
deaths causally related to treatment / all	0 / 3	0 / 5
Septic shock
subjects affected / exposed	2 / 2012 (0.10%)	4 / 2006 (0.20%)
occurrences causally related to treatment / all	0 / 3	0 / 4
deaths causally related to treatment / all	0 / 1	0 / 3
Submandibular abscess
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Tooth abscess
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	4 / 2012 (0.20%)	4 / 2006 (0.20%)
occurrences causally related to treatment / all	0 / 4	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Urosepsis
subjects affected / exposed	3 / 2012 (0.15%)	4 / 2006 (0.20%)
occurrences causally related to treatment / all	0 / 3	0 / 4
deaths causally related to treatment / all	0 / 1	0 / 2
Vestibular neuronitis
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Genital infection male
subjects affected / exposed	0 / 2012 (0.00%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Metabolism and nutrition disorders
Dehydration
subjects affected / exposed	2 / 2012 (0.10%)	2 / 2006 (0.10%)
occurrences causally related to treatment / all	0 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Diabetes mellitus
subjects affected / exposed	5 / 2012 (0.25%)	2 / 2006 (0.10%)
occurrences causally related to treatment / all	0 / 5	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Diabetic_ketoacidosis
subjects affected / exposed	1 / 2012 (0.05%)	1 / 2006 (0.05%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hyperglycaemia
subjects affected / exposed	2 / 2012 (0.10%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hyperkalaemia
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hypoglycaemia
subjects affected / exposed	2 / 2012 (0.10%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hypokalaemia
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hyponatraemia
subjects affected / exposed	0 / 2012 (0.00%)	2 / 2006 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Metabolic disorder
subjects affected / exposed	1 / 2012 (0.05%)	0 / 2006 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 0%

Non-serious adverse events	Ticagrelor	Prasugrel
Total subjects affected by non serious adverse events
subjects affected / exposed	0 / 2012 (0.00%)	0 / 2006 (0.00%)

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Were there any global substantial amendments to the protocol? Yes

10 Jun 2014

Protocol V 2.0 dated May 2014 (versus Protocol V 1.1) - Removal of Core lab - Secondary endpoints: Stent thrombosis according to ARC criteria (definite or probable) - Follow-up: time frame extended 30 (+10) days, 6 months (± 1 month), 12 months (± 1 month), long term outcome: 3-year (± 2 months) mortality (outpatient clinic, phone or letter) - Inclusion criteria: Pregnancy test removed - Exclusion criteria: Pregnancy test added, intracranial bleeding added - Study medication: Description adapted to SmPCs - Concomitant medication/ ASA/ Adjunct antithrombotic therapy: The initial dose of 150-500 mg was defined, if patients did not receive ASA within the past 12 hours. If a triple therapy is indicated, it is recommended to switch Ticagrelor or Prasugrel to Clopidogrel. - Laboratory: The heart enzymes should be taken at least twice and in case of a recurrent cardiac event. - Pharmacovigilance: o Information regarding documentation of (S)AEs and endpoints o Definition of averse events o Other medically important events o The term life threatening was explained in detail - Sample size calculation - ICF: Procedure with patients with cardiogenic shock was added - Endpoint Definitions were updated.

16 Dec 2015

Interruption of recruitment 17 Dec 2015

19 Jul 2016

Protocol V 4.0 dated 19 Jul 2016 - Added to Risk to benefit assessment: Therefore the risk of participating in this clinical trial for the patient is limited to the risk of randomization. - Primary endpoint: Description in more detail This endpoint consists of a time component and a status component. The former is measured in days between the date of randomization and • the date of the first event that occurs until (and including) the date of the final investigation after 12 months ± 1 months, or • the date of the final investigation after 12 months ± 1 months, if there was no event up to that point in time, or • the last follow-up date if there is no event up to that point in time and the 12 months ± 1 months measurement is missing. The corresponding status takes the value 1 if an event occurred and 0, otherwise. The last point in the previous listing indicates how missing values are handled. - Secondary endpoint: added Death within 12 months after randomization Myocardial infarction within 12 months after randomization Stroke within 12 months after randomization - Safety Reporting: Description in more detail. After one year of follow-up, only adverse events that are fatal or life threatening have to be reported. - Hypothesis testing: updated - Statistics: Primary endpoint: Analysis updated Secundary endpoint: Analysis updated Analysis after 2000 patients adapted

17 Oct 2016

Restart of recruitment 15 Nov 2016, dated 17 Oct 2016

Were there any global interruptions to the trial? Yes

Date	Interruption	Restart date
17 Dec 2015	Interruption of recruitment due to inspection findings (BfArM). Italian sites completed recruitment in Dec 2015.	15 Nov 2016

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

http://www.ncbi.nlm.nih.gov/pubmed/31475799
http://www.ncbi.nlm.nih.gov/pubmed/24371012

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Clinical trials

Clinical Trial Results:
PROSPECTIVE, RANDOMIZED TRIAL OF TICAGRELOR VERSUS PRASUGREL IN PATIENTS WITH ACUTE CORONARY SYNDROME Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment – ISAR-REACT 5

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Composite of death, myocardial infarction, stroke

Primary: Composite of death, myocardial infarction, stroke

Secondary: Death

Secondary: Death

Secondary: Myocardial infarction

Secondary: Myocardial infarction

Secondary: Stroke

Secondary: Stroke

Secondary: Definite or probable stent thrombosis

Secondary: Definite or probable stent thrombosis

Secondary: Safety endpoint (Bleeding BARC type 3, 4 or 5)

Secondary: Safety endpoint (Bleeding BARC type 3, 4 or 5)

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

Online references

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Clinical trials

Clinical Trial Results: PROSPECTIVE, RANDOMIZED TRIAL OF TICAGRELOR VERSUS PRASUGREL IN PATIENTS WITH ACUTE CORONARY SYNDROME Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment – ISAR-REACT 5

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Composite of death, myocardial infarction, stroke

Primary: Composite of death, myocardial infarction, stroke

Secondary: Death

Secondary: Death

Secondary: Myocardial infarction

Secondary: Myocardial infarction

Secondary: Stroke

Secondary: Stroke

Secondary: Definite or probable stent thrombosis

Secondary: Definite or probable stent thrombosis

Secondary: Safety endpoint (Bleeding BARC type 3, 4 or 5)

Secondary: Safety endpoint (Bleeding BARC type 3, 4 or 5)

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

Online references

More information

Clinical Trial Results:
PROSPECTIVE, RANDOMIZED TRIAL OF TICAGRELOR VERSUS PRASUGREL IN PATIENTS WITH ACUTE CORONARY SYNDROME Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment – ISAR-REACT 5