SHIFT: Effects of Ivabradine on Cardiovascular Events in Patients With Moderate to Severe Chronic Heart Failure and Left Ventricular Systolic Dysfunction. A Three-year International Multicentre Study
Sponsor
Institut de Recherches Internationales Servier (Other)
Overall Status
Completed
CT.gov ID
NCT02441218
Collaborator
(none)
6,505
2
2
43
3252.5
75.7
Study Details
Study Description
Brief Summary
The primary objective of this study is to demonstrate the superiority of ivabradine over placebo in the reduction of cardiovascular mortality or hospitalisation for worsening heart failure in patients with moderate to severe symptoms of chronic heart failure, a reduced left ventricular ejection fraction and currently receiving recommended therapy for this disease.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
6505 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Study Start Date
:
Sep 1, 2006
Actual Primary Completion Date
:
Apr 1, 2010
Actual Study Completion Date
:
Apr 1, 2010
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Ivabradine
|
Drug: Ivabradine
2.5mg, 5mg or 7.5mg tablets to be taken orally twice daily, at 12-hours intervals, in the morning and in the evening during meals up to 42 months.
|
| Placebo Comparator: Placebo
|
Drug: Placebo
Matching placebo tablets to be taken orally twice daily, at 12-hours intervals, in the morning and in the evening during meals up to 42 months.
|
Outcome Measures
Primary Outcome Measures
- Primary Composite Endpoint: First Event Among Cardiovascular Death (Including Death of Unknown Cause) or Hospitalization for Worsening Heart Failure. [All over the study (up to 42 months).]
Number of patients having experienced the Primary Composite Endpoint.
Secondary Outcome Measures
- Cardiovascular Death [From the date of randomization until the date of death, up to 42 months]
Component of the primary composite endpoint
- Hospitalisation for Worsening Heart Failure [From the date of randomization to the date of first documented hospitalisation, up to 42 months]
- All-cause Mortality [From the date of randomisation to death, up to 42 months.]
- Death From Heart Failure [From the date of randomisation to death, up to 42 months.]
Component of cardiovascular death
- Hospitalisation for Any Cause [From the date of randomisation to the date of first documented hospitalisation, up to 42 months]
- Hospitalisation for Cardiovascular Reason [From the date of randomisation to the first documented hospitalisation, up to 42 months]
- Unplanned Hospitalisation for Any Cause [From the date of randomisation to the first documented hospitalisation, up to 42 months]
- Unplanned Hospitalisation for CV Reason [From the date of randomisation to the first documented hospitalisation, up to 42 months.]
- Secondary Composite Endpoint [From the date of randomisation to the date of the first event, up to 42 months]
CV death, hospitalisation for worsening HF or hospitalisation for non-fatal myocardial infarction
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Symptomatic Chronic heart failure (NYHA II, III or IV)
-
Left ventricular systolic dysfunction (LVEF ≤ 35%)
-
Sinus rhythm and resting heart rate ≥ 70 bpm
-
Optimal and unchanged CHF medications or dosages
Exclusion Criteria:
-
Unstable condition within previous 4 weeks
-
Myocardial infarction or coronary revascularisation within previous 2 months
-
Stroke or transient cerebral ischaemia within previous 4 weeks
-
Congenital heart disease
-
Severe valvular disease
-
Active myocarditis
-
Permanent atrial fibrillation or flutter
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Hôpital Pitié-Salpétrière | Paris | France | 75013 | |
| 2 | Göteborg University | Göteborg | Sweden | S 41685 |
Sponsors and Collaborators
- Institut de Recherches Internationales Servier
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
Institut de Recherches Internationales Servier
ClinicalTrials.gov Identifier:
NCT02441218
Other Study ID Numbers:
- CL3-16257-063
- 2006-000708-18
First Posted:
May 12, 2015
Last Update Posted:
Jan 3, 2020
Last Verified:
Jan 1, 2020
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | The target population was adult patients with stable, moderate to severe chronic heart failure (CHF) and left ventricular systolic dysfunction, with optimal and unchanged CHF medications and dosages for ≥ 4 weeks. |
|---|---|
| Pre-assignment Detail | Following a run-in period of two weeks during which no study treatment was dispensed, the participants were randomised to receive ivabradine or placebo in addition to their usual cardiovascular treatment in double-blind treatment period. |
| Arm/Group Title | Ivabradine | Placebo |
|---|---|---|
| Arm/Group Description | Ivabradine: 2.5mg, 5mg or 7.5mg tablets to be taken orally twice daily, at 12-hours intervals, in the morning and in the evening during meals up to 42 months. | Placebo: Matching placebo tablets to be taken orally twice daily, at 12-hours intervals, in the morning and in the evening during meals up to 42 months. |
| Period Title: Overall Study | ||
| STARTED | 3241 | 3264 |
| COMPLETED | 2663 | 2652 |
| NOT COMPLETED | 578 | 612 |
Baseline Characteristics
| Arm/Group Title | Ivabradine | Placebo | Total |
|---|---|---|---|
| Arm/Group Description | Ivabradine: 2.5mg, 5mg or 7.5mg tablets to be taken orally twice daily, at 12-hours intervals, in the morning and in the evening during meals up to 42 months. | Placebo: Matching placebo tablets to be taken orally twice daily, at 12-hours intervals, in the morning and in the evening during meals up to 42 months. | Total of all reporting groups |
| Overall Participants | 3241 | 3264 | 6505 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
60.7
(11.2)
|
60.1
(11.5)
|
60.4
(11.4)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
779
24%
|
756
23.2%
|
1535
23.6%
|
| Male |
2462
76%
|
2508
76.8%
|
4970
76.4%
|
| Beta-blocker intake at randomization (participants) [Number] | |||
| Yes |
2897
89.4%
|
2923
89.6%
|
5820
89.5%
|
| No |
344
10.6%
|
341
10.4%
|
685
10.5%
|
Outcome Measures
| Title | Primary Composite Endpoint: First Event Among Cardiovascular Death (Including Death of Unknown Cause) or Hospitalization for Worsening Heart Failure. |
|---|---|
| Description | Number of patients having experienced the Primary Composite Endpoint. |
| Time Frame | All over the study (up to 42 months). |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Ivabradine | Placebo |
|---|---|---|
| Arm/Group Description | Ivabradine: 2.5mg, 5mg or 7.5mg tablets to be taken orally twice daily, at 12-hours intervals, in the morning and in the evening during meals up to 42 months. | Placebo: Matching placebo tablets to be taken orally twice daily, at 12-hours intervals, in the morning and in the evening during meals up to 42 months. |
| Measure Participants | 3241 | 3264 |
| Number [participants] |
793
24.5%
|
937
28.7%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Ivabradine, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Regression, Cox | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.82 | |
| Confidence Interval |
(2-Sided) 95% 0.75 to 0.90 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Estimate of the hazard ratio between treatment groups based on an adjusted Cox proportional hazards model with beta-blocker intake at randomisation as a covariate. P-value: Wald test | |
| Title | Cardiovascular Death |
|---|---|
| Description | Component of the primary composite endpoint |
| Time Frame | From the date of randomization until the date of death, up to 42 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Ivabradine | Placebo |
|---|---|---|
| Arm/Group Description | Ivabradine: 2.5mg, 5mg or 7.5mg tablets to be taken orally twice daily, at 12-hours intervals, in the morning and in the evening during meals up to 42 months. | Placebo: Matching placebo tablets to be taken orally twice daily, at 12-hours intervals, in the morning and in the evening during meals up to 42 months. |
| Measure Participants | 3241 | 3264 |
| Number [participants] |
449
13.9%
|
491
15%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Ivabradine, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.128 |
| Comments | ||
| Method | Regression, Cox | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.91 | |
| Confidence Interval |
(2-Sided) 95% 0.80 to 1.03 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Estimate of the hazard ratio between treatment groups based on an adjusted Cox proportional hazards model with beta-blocker intake at randomisation as a covariate. P-value: Wald test | |
| Title | Hospitalisation for Worsening Heart Failure |
|---|---|
| Description | |
| Time Frame | From the date of randomization to the date of first documented hospitalisation, up to 42 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Ivabradine | Placebo |
|---|---|---|
| Arm/Group Description | Ivabradine: 2.5mg, 5mg or 7.5mg tablets to be taken orally twice daily, at 12-hours intervals, in the morning and in the evening during meals up to 42 months. | Placebo: Matching placebo tablets to be taken orally twice daily, at 12-hours intervals, in the morning and in the evening during meals up to 42 months. |
| Measure Participants | 3241 | 3264 |
| Number [participants] |
514
15.9%
|
672
20.6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Ivabradine, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | < 0.0001 |
| Comments | ||
| Method | Regression, Cox | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.74 | |
| Confidence Interval |
(2-Sided) 95% 0.66 to 0.83 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Estimate of the hazard ratio between treatment groups based on an adjusted Cox proportional hazards model with beta-blocker intake at randomisation as a covariate. P-value: Wald test | |
| Title | All-cause Mortality |
|---|---|
| Description | |
| Time Frame | From the date of randomisation to death, up to 42 months. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Ivabradine | Placebo |
|---|---|---|
| Arm/Group Description | Ivabradine: 2.5mg, 5mg or 7.5mg tablets to be taken orally twice daily, at 12-hours intervals, in the morning and in the evening during meals up to 42 months. | Placebo: Matching placebo tablets to be taken orally twice daily, at 12-hours intervals, in the morning and in the evening during meals up to 42 months. |
| Measure Participants | 3241 | 3264 |
| Number [participants] |
503
15.5%
|
552
16.9%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Ivabradine, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.092 |
| Comments | ||
| Method | Regression, Cox | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.90 | |
| Confidence Interval |
(2-Sided) 95% 0.80 to 1.02 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Estimate of the hazard ratio between treatment groups based on an adjusted Cox proportional hazards model with beta-blocker intake at randomisation as a covariate. P-value: Wald test | |
| Title | Death From Heart Failure |
|---|---|
| Description | Component of cardiovascular death |
| Time Frame | From the date of randomisation to death, up to 42 months. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Ivabradine | Placebo |
|---|---|---|
| Arm/Group Description | Ivabradine: 2.5mg, 5mg or 7.5mg tablets to be taken orally twice daily, at 12-hours intervals, in the morning and in the evening during meals up to 42 months. | Placebo: Matching placebo tablets to be taken orally twice daily, at 12-hours intervals, in the morning and in the evening during meals up to 42 months. |
| Measure Participants | 3241 | 3264 |
| Number [participants] |
113
3.5%
|
151
4.6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Ivabradine, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0140 |
| Comments | ||
| Method | Regression, Cox | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.74 | |
| Confidence Interval |
(2-Sided) 95% 0.58 to 0.94 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Estimate of the hazard ratio between treatment groups based on an adjusted Cox proportional hazards model with beta-blocker intake at randomisation as a covariate. P-value: Wald test | |
| Title | Hospitalisation for Any Cause |
|---|---|
| Description | |
| Time Frame | From the date of randomisation to the date of first documented hospitalisation, up to 42 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Ivabradine | Placebo |
|---|---|---|
| Arm/Group Description | Ivabradine: 2.5mg, 5mg or 7.5mg tablets to be taken orally twice daily, at 12-hours intervals, in the morning and in the evening during meals up to 42 months. | Placebo: Matching placebo tablets to be taken orally twice daily, at 12-hours intervals, in the morning and in the evening during meals up to 42 months. |
| Measure Participants | 3241 | 3264 |
| Number [participants] |
1231
38%
|
1356
41.5%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Ivabradine, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0027 |
| Comments | ||
| Method | Regression, Cox | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.89 | |
| Confidence Interval |
(2-Sided) 95% 0.82 to 0.96 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Estimate of the hazard ratio between treatment groups based on an adjusted Cox proportional hazards model with beta-blocker intake at randomisation as a covariate. P-value: Wald test | |
| Title | Hospitalisation for Cardiovascular Reason |
|---|---|
| Description | |
| Time Frame | From the date of randomisation to the first documented hospitalisation, up to 42 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Ivabradine | Placebo |
|---|---|---|
| Arm/Group Description | Ivabradine: 2.5mg, 5mg or 7.5mg tablets to be taken orally twice daily, at 12-hours intervals, in the morning and in the evening during meals up to 42 months. | Placebo: Matching placebo tablets to be taken orally twice daily, at 12-hours intervals, in the morning and in the evening during meals up to 42 months. |
| Measure Participants | 3241 | 3264 |
| Number [participants] |
977
30.1%
|
1122
34.4%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Ivabradine, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0002 |
| Comments | ||
| Method | Regression, Cox | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.85 | |
| Confidence Interval |
(2-Sided) 95% 0.78 to 0.92 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Estimate of the hazard ratio between treatment groups based on an adjusted Cox proportional hazards model with beta-blocker intake at randomisation as a covariate. P-value: Wald test | |
| Title | Unplanned Hospitalisation for Any Cause |
|---|---|
| Description | |
| Time Frame | From the date of randomisation to the first documented hospitalisation, up to 42 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Ivabradine | Placebo |
|---|---|---|
| Arm/Group Description | Ivabradine: 2.5mg, 5mg or 7.5mg tablets to be taken orally twice daily, at 12-hours intervals, in the morning and in the evening during meals up to 42 months. | Placebo: Matching placebo tablets to be taken orally twice daily, at 12-hours intervals, in the morning and in the evening during meals up to 42 months. |
| Measure Participants | 3241 | 3264 |
| Number [participants] |
1137
35.1%
|
1264
38.7%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Ivabradine, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0013 |
| Comments | ||
| Method | Regression, Cox | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.88 | |
| Confidence Interval |
(2-Sided) 95% 0.81 to 0.95 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Estimate of the hazard ratio between treatment groups based on an adjusted Cox proportional hazards model with beta-blocker intake at randomisation as a covariate. P-value: Wald test | |
| Title | Unplanned Hospitalisation for CV Reason |
|---|---|
| Description | |
| Time Frame | From the date of randomisation to the first documented hospitalisation, up to 42 months. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Ivabradine | Placebo |
|---|---|---|
| Arm/Group Description | Ivabradine: 2.5mg, 5mg or 7.5mg tablets to be taken orally twice daily, at 12-hours intervals, in the morning and in the evening during meals up to 42 months. | Placebo: Matching placebo tablets to be taken orally twice daily, at 12-hours intervals, in the morning and in the evening during meals up to 42 months. |
| Measure Participants | 3241 | 3264 |
| Number [participants] |
909
28%
|
1047
32.1%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Ivabradine, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0002 |
| Comments | ||
| Method | Regression, Cox | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.84 | |
| Confidence Interval |
(2-Sided) 95% 0.77 to 0.92 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Estimate of the hazard ratio between treatment groups based on an adjusted Cox proportional hazards model with beta-blocker intake at randomisation as a covariate. P-value: Wald test | |
| Title | Secondary Composite Endpoint |
|---|---|
| Description | CV death, hospitalisation for worsening HF or hospitalisation for non-fatal myocardial infarction |
| Time Frame | From the date of randomisation to the date of the first event, up to 42 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Ivabradine | Placebo |
|---|---|---|
| Arm/Group Description | Ivabradine: 2.5mg, 5mg or 7.5mg tablets to be taken orally twice daily, at 12-hours intervals, in the morning and in the evening during meals up to 42 months. | Placebo: Matching placebo tablets to be taken orally twice daily, at 12-hours intervals, in the morning and in the evening during meals up to 42 months. |
| Measure Participants | 3241 | 3264 |
| Number [participants] |
825
25.5%
|
979
30%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Ivabradine, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | < 0.0001 |
| Comments | ||
| Method | Regression, Cox | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.82 | |
| Confidence Interval |
(2-Sided) 95% 0.74 to 0.89 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Estimate of the hazard ratio between treatment groups based on an adjusted Cox proportional hazards model with beta-blocker intake at randomisation as a covariate. P-value: Wald test | |
Adverse Events
| Time Frame | From randomisation to death, up to 42 months | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | The Randomised Set consisted of 6505 patients (3241 patients in the ivabradine group and 3264 patients in the placebo group). The Safety Set consisted of 6492 patients: 13 randomised patients were excluded from the Safety Set because they did not take any study drug (9 patients in the ivabradine group and 4 patients in the placebo group). | |||
| Arm/Group Title | Ivabradine | Placebo | ||
| Arm/Group Description | Ivabradine: 2.5mg, 5mg or 7.5mg tablets to be taken orally twice daily, at 12-hours intervals, in the morning and in the evening during meals up to 42 months. | Placebo: Matching placebo tablets to be taken orally twice daily, at 12-hours intervals, in the morning and in the evening during meals up to 42 months. | ||
All Cause Mortality |
||||
| Ivabradine | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Ivabradine | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1369/3232 (42.4%) | 1481/3260 (45.4%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 6/3232 (0.2%) | 6 | 8/3260 (0.2%) | 8 |
| Hypochromic anaemia | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Iron deficiency anaemia | 0/3232 (0%) | 0 | 3/3260 (0.1%) | 3 |
| Lymphadenopathy mediastinal | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Microcytic anaemia | 1/3232 (0%) | 1 | 1/3260 (0%) | 1 |
| Nephrogenic anaemia | 1/3232 (0%) | 1 | 1/3260 (0%) | 1 |
| Spleen disorder | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Thrombocytopenia | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Cardiac disorders | ||||
| Acute coronary syndrome | 9/3232 (0.3%) | 11 | 14/3260 (0.4%) | 14 |
| Acute myocardial infarction | 62/3232 (1.9%) | 65 | 54/3260 (1.7%) | 61 |
| Adams-Stokes syndrome | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Angina pectoris | 51/3232 (1.6%) | 61 | 55/3260 (1.7%) | 60 |
| Angina unstable | 113/3232 (3.5%) | 140 | 119/3260 (3.7%) | 139 |
| Arteriosclerosis coronary artery | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Atrial fibrillation | 126/3232 (3.9%) | 139 | 106/3260 (3.3%) | 114 |
| Atrial flutter | 22/3232 (0.7%) | 22 | 19/3260 (0.6%) | 20 |
| Atrial tachycardia | 1/3232 (0%) | 1 | 1/3260 (0%) | 1 |
| Atrial thrombosis | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Atrioventricular block complete | 9/3232 (0.3%) | 9 | 2/3260 (0.1%) | 2 |
| Atrioventricular block first degree | 0/3232 (0%) | 0 | 2/3260 (0.1%) | 2 |
| Atrioventricular block second degree | 7/3232 (0.2%) | 7 | 4/3260 (0.1%) | 4 |
| Atrioventricular block third degree | 8/3232 (0.2%) | 8 | 2/3260 (0.1%) | 2 |
| Bradycardia | 15/3232 (0.5%) | 15 | 2/3260 (0.1%) | 2 |
| Cardiac aneurysm | 1/3232 (0%) | 1 | 1/3260 (0%) | 1 |
| Cardiac arrest | 2/3232 (0.1%) | 2 | 1/3260 (0%) | 1 |
| Cardiac failure | 506/3232 (15.7%) | 766 | 665/3260 (20.4%) | 1093 |
| Cardiac failure acute | 12/3232 (0.4%) | 13 | 5/3260 (0.2%) | 5 |
| Cardiac failure congestive | 17/3232 (0.5%) | 21 | 19/3260 (0.6%) | 21 |
| Cardio-respiratory distress | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Cardiogenic shock | 15/3232 (0.5%) | 15 | 16/3260 (0.5%) | 16 |
| Cardiomyopathy | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Conduction disorder | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Congestive cardiomyopathy | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Cor pulmonale | 1/3232 (0%) | 4 | 0/3260 (0%) | 0 |
| Coronary artery disease | 5/3232 (0.2%) | 5 | 5/3260 (0.2%) | 5 |
| Coronary artery insufficiency | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Coronary artery occlusion | 0/3232 (0%) | 0 | 3/3260 (0.1%) | 3 |
| Coronary artery stenosis | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Intracardiac thrombus | 2/3232 (0.1%) | 2 | 1/3260 (0%) | 1 |
| Ischaemic cardiomyopathy | 1/3232 (0%) | 1 | 1/3260 (0%) | 1 |
| Left ventricular failure | 3/3232 (0.1%) | 3 | 1/3260 (0%) | 1 |
| Mitral valve incompetence | 2/3232 (0.1%) | 2 | 3/3260 (0.1%) | 3 |
| Mitral valve stenosis | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Myocardial infarction | 57/3232 (1.8%) | 63 | 51/3260 (1.6%) | 51 |
| Myocardial ischaemia | 2/3232 (0.1%) | 3 | 3/3260 (0.1%) | 3 |
| Nodal arrhythmia | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Pericardial effusion | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Pericarditis | 1/3232 (0%) | 1 | 1/3260 (0%) | 1 |
| Rhythm idioventricular | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Sick sinus syndrome | 5/3232 (0.2%) | 5 | 0/3260 (0%) | 0 |
| Sinoatrial block | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Supraventricular extrasystoles | 2/3232 (0.1%) | 2 | 1/3260 (0%) | 1 |
| Supraventricular tachycardia | 4/3232 (0.1%) | 4 | 5/3260 (0.2%) | 5 |
| Torsade de pointes | 2/3232 (0.1%) | 2 | 0/3260 (0%) | 0 |
| Tricuspid valve incompetence | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Ventricular arrhythmia | 3/3232 (0.1%) | 3 | 5/3260 (0.2%) | 5 |
| Ventricular dysfunction | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Ventricular extrasystoles | 15/3232 (0.5%) | 15 | 9/3260 (0.3%) | 9 |
| Ventricular fibrillation | 20/3232 (0.6%) | 21 | 11/3260 (0.3%) | 11 |
| Ventricular tachyarrhythmia | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Ventricular tachycardia | 31/3232 (1%) | 34 | 46/3260 (1.4%) | 52 |
| Congenital, familial and genetic disorders | ||||
| Gastrointestinal angiodysplasia haemorrhagic | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Ear and labyrinth disorders | ||||
| Acute vestibular syndrome | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Vertigo | 0/3232 (0%) | 0 | 3/3260 (0.1%) | 3 |
| Vertigo positional | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Endocrine disorders | ||||
| Goitre | 1/3232 (0%) | 1 | 2/3260 (0.1%) | 2 |
| Hyperparathyroidism primary | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Hyperthyroidism | 2/3232 (0.1%) | 2 | 1/3260 (0%) | 1 |
| Eye disorders | ||||
| Cataract | 9/3232 (0.3%) | 11 | 7/3260 (0.2%) | 7 |
| Cataract cortical | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Diabetic retinopathy | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Glaucoma | 3/3232 (0.1%) | 4 | 1/3260 (0%) | 1 |
| Iridocyclitis | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Lens dislocation | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Open angle glaucoma | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Presbyopia | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Retinal artery embolism | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Retinal artery occlusion | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Retinal detachment | 1/3232 (0%) | 1 | 1/3260 (0%) | 1 |
| Retinopathy proliferative | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Ulcerative keratitis | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Uveitis | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Vision blurred | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Vitreous haemorrhage | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Gastrointestinal disorders | ||||
| Abdominal distension | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Abdominal hernia | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Abdominal pain | 1/3232 (0%) | 1 | 2/3260 (0.1%) | 3 |
| Abdominal pain upper | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Anal fistula | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Ascites | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Colitis | 2/3232 (0.1%) | 2 | 0/3260 (0%) | 0 |
| Colonic haematoma | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Colonic polyp | 2/3232 (0.1%) | 2 | 2/3260 (0.1%) | 2 |
| Constipation | 0/3232 (0%) | 0 | 2/3260 (0.1%) | 2 |
| Diarrhoea | 1/3232 (0%) | 1 | 5/3260 (0.2%) | 5 |
| Disbacteriosis | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Diverticulum duodenal | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Diverticulum intestinal | 1/3232 (0%) | 1 | 2/3260 (0.1%) | 2 |
| Diverticulum intestinal haemorrhagic | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Duodenal ulcer haemorrhage | 4/3232 (0.1%) | 4 | 2/3260 (0.1%) | 2 |
| Duodenitis | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Dyspepsia | 2/3232 (0.1%) | 2 | 0/3260 (0%) | 0 |
| Dysphagia | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Enteritis | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Enterocolitis | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Erosive duodenitis | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Erosive oesophagitis | 0/3232 (0%) | 0 | 2/3260 (0.1%) | 2 |
| Femoral hernia | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Food poisoning | 1/3232 (0%) | 1 | 1/3260 (0%) | 1 |
| Gastric disorder | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Gastric haemorrhage | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Gastric polyps | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Gastric ulcer | 3/3232 (0.1%) | 3 | 1/3260 (0%) | 1 |
| Gastric ulcer haemorrhage | 3/3232 (0.1%) | 3 | 3/3260 (0.1%) | 3 |
| Gastric ulcer perforation | 2/3232 (0.1%) | 2 | 0/3260 (0%) | 0 |
| Gastritis | 4/3232 (0.1%) | 4 | 4/3260 (0.1%) | 4 |
| Gastritis atrophic | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Gastritis erosive | 0/3232 (0%) | 0 | 3/3260 (0.1%) | 3 |
| Gastritis haemorrhagic | 2/3232 (0.1%) | 3 | 0/3260 (0%) | 0 |
| Gastroduodenal ulcer | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Gastroduodenitis | 2/3232 (0.1%) | 2 | 1/3260 (0%) | 1 |
| Gastrointestinal disorder | 0/3232 (0%) | 0 | 2/3260 (0.1%) | 2 |
| Gastrointestinal erosion | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Gastrointestinal haemorrhage | 4/3232 (0.1%) | 4 | 5/3260 (0.2%) | 5 |
| Gastrointestinal perforation | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Gastrooesophageal reflux disease | 1/3232 (0%) | 1 | 1/3260 (0%) | 1 |
| Haemorrhoidal haemorrhage | 2/3232 (0.1%) | 2 | 2/3260 (0.1%) | 2 |
| Haemorrhoids | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Hiatus hernia | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Ileus | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Impaired gastric emptying | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Inguinal hernia | 8/3232 (0.2%) | 8 | 8/3260 (0.2%) | 9 |
| Inguinal hernia, obstructive | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Intestinal ischaemia | 1/3232 (0%) | 1 | 1/3260 (0%) | 1 |
| Intestinal obstruction | 0/3232 (0%) | 0 | 3/3260 (0.1%) | 3 |
| Mallory-Weiss syndrome | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Mechanical ileus | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Megacolon | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Melaena | 0/3232 (0%) | 0 | 2/3260 (0.1%) | 2 |
| Mesenteric artery thrombosis | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Pancreatic cyst | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Pancreatitis | 3/3232 (0.1%) | 3 | 1/3260 (0%) | 1 |
| Pancreatitis acute | 5/3232 (0.2%) | 5 | 5/3260 (0.2%) | 5 |
| Pancreatitis chronic | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Pancreatitis necrotising | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Peritonitis | 1/3232 (0%) | 1 | 5/3260 (0.2%) | 5 |
| Polyp colorectal | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Rectal haemorrhage | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Reflux oesophagitis | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Sigmoiditis | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Subileus | 1/3232 (0%) | 1 | 2/3260 (0.1%) | 2 |
| Thrombosis mesenteric vessel | 1/3232 (0%) | 1 | 1/3260 (0%) | 1 |
| Umbilical hernia | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Upper gastrointestinal haemorrhage | 6/3232 (0.2%) | 6 | 1/3260 (0%) | 1 |
| Volvulus | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Vomiting | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| General disorders | ||||
| Accidental death | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Cardiac death | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Chest pain | 5/3232 (0.2%) | 5 | 4/3260 (0.1%) | 7 |
| Death | 4/3232 (0.1%) | 4 | 1/3260 (0%) | 1 |
| Fatigue | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Hyperthermia | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Implant site inflammation | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Implant site ulcer | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Non-cardiac chest pain | 5/3232 (0.2%) | 5 | 2/3260 (0.1%) | 4 |
| Oedema peripheral | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Pain | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Pyrexia | 1/3232 (0%) | 1 | 1/3260 (0%) | 1 |
| Sudden cardiac death | 73/3232 (2.3%) | 73 | 68/3260 (2.1%) | 68 |
| Sudden death | 111/3232 (3.4%) | 111 | 119/3260 (3.7%) | 119 |
| Systemic inflammatory response syndrome | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Hepatobiliary disorders | ||||
| Bile duct stone | 0/3232 (0%) | 0 | 2/3260 (0.1%) | 2 |
| Biliary colic | 2/3232 (0.1%) | 2 | 0/3260 (0%) | 0 |
| Biliary dilatation | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Cholangitis | 0/3232 (0%) | 0 | 2/3260 (0.1%) | 2 |
| Cholecystitis | 7/3232 (0.2%) | 7 | 11/3260 (0.3%) | 11 |
| Cholecystitis acute | 5/3232 (0.2%) | 5 | 9/3260 (0.3%) | 9 |
| Cholelithiasis | 6/3232 (0.2%) | 6 | 5/3260 (0.2%) | 5 |
| Cholestasis | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Cytolytic hepatitis | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Hepatic cirrhosis | 3/3232 (0.1%) | 3 | 3/3260 (0.1%) | 3 |
| Hepatic congestion | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Hepatic function abnormal | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Hepatic steatosis | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Hepatitis cholestatic | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Hepatitis toxic | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Hepatorenal failure | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Hyperbilirubinaemia | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Jaundice | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Post cholecystectomy syndrome | 0/3232 (0%) | 0 | 2/3260 (0.1%) | 2 |
| Immune system disorders | ||||
| Allergic oedema | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Anaphylactic shock | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Cryoglobulinaemia | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Infections and infestations | ||||
| Abdominal sepsis | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Abdominal wall abscess | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Abscess limb | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Abscess oral | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Appendicitis | 2/3232 (0.1%) | 2 | 2/3260 (0.1%) | 2 |
| Ascites infection | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Bacterial sepsis | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Bronchiectasis | 0/3232 (0%) | 0 | 2/3260 (0.1%) | 2 |
| Bronchitis | 3/3232 (0.1%) | 3 | 5/3260 (0.2%) | 5 |
| Bronchitis acute | 10/3232 (0.3%) | 11 | 18/3260 (0.6%) | 20 |
| Bronchitis acute viral | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Bronchitis chronic | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Bronchopneumonia | 7/3232 (0.2%) | 8 | 7/3260 (0.2%) | 8 |
| Bursitis infective | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Candida sepsis | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Cellulitis | 5/3232 (0.2%) | 5 | 6/3260 (0.2%) | 6 |
| Clostridium colitis | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Device related infection | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Diabetic foot infection | 1/3232 (0%) | 1 | 4/3260 (0.1%) | 4 |
| Diabetic gangrene | 5/3232 (0.2%) | 5 | 5/3260 (0.2%) | 6 |
| Diverticulitis | 0/3232 (0%) | 0 | 4/3260 (0.1%) | 5 |
| Ear infection | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Endocarditis | 2/3232 (0.1%) | 2 | 0/3260 (0%) | 0 |
| Epidemic nephropathy | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Epstein-Barr virus infection | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Erysipelas | 5/3232 (0.2%) | 5 | 7/3260 (0.2%) | 8 |
| Escherichia urinary tract infection | 1/3232 (0%) | 1 | 1/3260 (0%) | 1 |
| Gangrene | 1/3232 (0%) | 1 | 1/3260 (0%) | 1 |
| Gastroenteritis | 4/3232 (0.1%) | 4 | 5/3260 (0.2%) | 5 |
| Gastroenteritis enteroviral | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Gastroenteritis viral | 0/3232 (0%) | 0 | 2/3260 (0.1%) | 2 |
| Gastrointestinal infection | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Graft infection | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Hepatitis B | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Hepatitis C | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Herpes zoster | 2/3232 (0.1%) | 2 | 0/3260 (0%) | 0 |
| Infected skin ulcer | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Infection | 1/3232 (0%) | 1 | 3/3260 (0.1%) | 3 |
| Influenza | 1/3232 (0%) | 1 | 2/3260 (0.1%) | 2 |
| Intervertebral discitis | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Laryngitis | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Lobar pneumonia | 4/3232 (0.1%) | 4 | 4/3260 (0.1%) | 4 |
| Lower respiratory tract infection | 2/3232 (0.1%) | 3 | 4/3260 (0.1%) | 4 |
| Lower respiratory tract infection viral | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Lung abscess | 1/3232 (0%) | 1 | 1/3260 (0%) | 1 |
| Lung infection | 4/3232 (0.1%) | 5 | 5/3260 (0.2%) | 6 |
| Lung infection pseudomonal | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Malaria | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Necrotising fasciitis | 1/3232 (0%) | 1 | 1/3260 (0%) | 1 |
| Obstructive chronic bronchitis with acute exacerbation | 2/3232 (0.1%) | 2 | 2/3260 (0.1%) | 4 |
| Orchitis | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Oropharyngeal candidiasis | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Osteomyelitis | 3/3232 (0.1%) | 4 | 3/3260 (0.1%) | 3 |
| Otitis media chronic | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Perianal abscess | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Peritoneal tuberculosis | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Pneumonia | 70/3232 (2.2%) | 79 | 65/3260 (2%) | 69 |
| Pneumonia bacterial | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Pneumonia klebsiella | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Pneumonia primary atypical | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Pneumonia staphylococcal | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Post procedural cellulitis | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Postoperative infection | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Postoperative wound infection | 2/3232 (0.1%) | 3 | 1/3260 (0%) | 1 |
| Pulmonary sepsis | 1/3232 (0%) | 1 | 2/3260 (0.1%) | 2 |
| Pulmonary tuberculosis | 3/3232 (0.1%) | 3 | 1/3260 (0%) | 1 |
| Purulent synovitis | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Pyelonephritis | 3/3232 (0.1%) | 3 | 2/3260 (0.1%) | 2 |
| Pyelonephritis acute | 0/3232 (0%) | 0 | 3/3260 (0.1%) | 3 |
| Pyelonephritis chronic | 4/3232 (0.1%) | 4 | 1/3260 (0%) | 1 |
| Pyonephrosis | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Respiratory tract infection | 7/3232 (0.2%) | 7 | 7/3260 (0.2%) | 8 |
| Respiratory tract infection bacterial | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Respiratory tract infection viral | 1/3232 (0%) | 1 | 1/3260 (0%) | 1 |
| Salmonellosis | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Sepsis | 4/3232 (0.1%) | 4 | 5/3260 (0.2%) | 5 |
| Septic shock | 1/3232 (0%) | 1 | 3/3260 (0.1%) | 3 |
| Sinusitis | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Staphylococcal bacteraemia | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Staphylococcal infection | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Staphylococcal sepsis | 3/3232 (0.1%) | 3 | 0/3260 (0%) | 0 |
| Tracheobronchitis | 1/3232 (0%) | 1 | 2/3260 (0.1%) | 2 |
| Tuberculosis | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Upper respiratory tract infection | 3/3232 (0.1%) | 3 | 2/3260 (0.1%) | 2 |
| Urinary tract infection | 4/3232 (0.1%) | 4 | 5/3260 (0.2%) | 5 |
| Urinary tract infection bacterial | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Urosepsis | 1/3232 (0%) | 1 | 3/3260 (0.1%) | 3 |
| Viral infection | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Wound infection | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Injury, poisoning and procedural complications | ||||
| Alcohol poisoning | 1/3232 (0%) | 1 | 1/3260 (0%) | 2 |
| Ankle fracture | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Cardiac pacemaker malfunction | 3/3232 (0.1%) | 3 | 3/3260 (0.1%) | 3 |
| Cerebral haemorrhage traumatic | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Chest injury | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Clavicle fracture | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Closed head injury | 0/3232 (0%) | 0 | 2/3260 (0.1%) | 2 |
| Coronary artery restenosis | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Device dislocation | 1/3232 (0%) | 1 | 3/3260 (0.1%) | 3 |
| Diaphragmatic injury | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Fall | 5/3232 (0.2%) | 5 | 3/3260 (0.1%) | 3 |
| Femoral neck fracture | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Femur fracture | 7/3232 (0.2%) | 8 | 4/3260 (0.1%) | 5 |
| Fibula fracture | 1/3232 (0%) | 1 | 1/3260 (0%) | 1 |
| Forearm fracture | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Foreign body in eye | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Haemothorax | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Hand fracture | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Head injury | 4/3232 (0.1%) | 4 | 0/3260 (0%) | 0 |
| Hip fracture | 1/3232 (0%) | 1 | 2/3260 (0.1%) | 2 |
| Humerus fracture | 2/3232 (0.1%) | 2 | 2/3260 (0.1%) | 2 |
| Implantable defibrillator malfunction | 6/3232 (0.2%) | 6 | 5/3260 (0.2%) | 5 |
| Incisional hernia | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Intervertebral disc injury | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Joint injury | 1/3232 (0%) | 1 | 1/3260 (0%) | 1 |
| Lower limb fracture | 2/3232 (0.1%) | 2 | 1/3260 (0%) | 1 |
| Lumbar vertebral fracture | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Multiple drug overdose accidental | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Multiple fractures | 2/3232 (0.1%) | 2 | 0/3260 (0%) | 0 |
| Operative haemorrhage | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Pacemaker complication | 2/3232 (0.1%) | 2 | 0/3260 (0%) | 0 |
| Polytraumatism | 1/3232 (0%) | 1 | 1/3260 (0%) | 1 |
| Post procedural complication | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Post procedural haematoma | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Post procedural haemorrhage | 1/3232 (0%) | 1 | 2/3260 (0.1%) | 2 |
| Postoperative hernia | 1/3232 (0%) | 1 | 4/3260 (0.1%) | 4 |
| Procedural hypotension | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Renal injury | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Rib fracture | 1/3232 (0%) | 1 | 1/3260 (0%) | 1 |
| Road traffic accident | 1/3232 (0%) | 1 | 3/3260 (0.1%) | 3 |
| Scrotal haematoma | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Skeletal injury | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Spinal compression fracture | 1/3232 (0%) | 1 | 1/3260 (0%) | 1 |
| Stent occlusion | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Subdural haematoma | 2/3232 (0.1%) | 2 | 3/3260 (0.1%) | 3 |
| Tendon rupture | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Therapeutic agent toxicity | 5/3232 (0.2%) | 5 | 1/3260 (0%) | 1 |
| Tibia fracture | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Tracheostomy malfunction | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Traumatic brain injury | 1/3232 (0%) | 1 | 3/3260 (0.1%) | 3 |
| Traumatic haematoma | 0/3232 (0%) | 0 | 2/3260 (0.1%) | 2 |
| Urinary bladder rupture | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Vascular graft occlusion | 1/3232 (0%) | 1 | 1/3260 (0%) | 1 |
| Wound evisceration | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Wrist fracture | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Investigations | ||||
| Anticoagulation drug level above therapeutic | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Arteriogram | 2/3232 (0.1%) | 2 | 0/3260 (0%) | 0 |
| Arteriogram coronary | 24/3232 (0.7%) | 24 | 12/3260 (0.4%) | 13 |
| Blood chloride decreased | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Blood potassium increased | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Carcinoembryonic antigen increased | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Cardiac electrophysiologic study | 0/3232 (0%) | 0 | 3/3260 (0.1%) | 3 |
| Cardiac pacemaker evaluation | 1/3232 (0%) | 1 | 1/3260 (0%) | 1 |
| Cardiovascular evaluation | 27/3232 (0.8%) | 32 | 27/3260 (0.8%) | 31 |
| Catheterisation cardiac | 0/3232 (0%) | 0 | 5/3260 (0.2%) | 6 |
| Coagulation time prolonged | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Colonoscopy | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Electrocardiogram abnormal | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Haemoglobin decreased | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Heart rate decreased | 3/3232 (0.1%) | 3 | 0/3260 (0%) | 0 |
| Hysteroscopy | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Investigation | 1/3232 (0%) | 1 | 2/3260 (0.1%) | 2 |
| Nephrological examination | 1/3232 (0%) | 1 | 1/3260 (0%) | 1 |
| Pregnancy test positive | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Sleep study | 1/3232 (0%) | 1 | 1/3260 (0%) | 1 |
| Transplant evaluation | 2/3232 (0.1%) | 2 | 5/3260 (0.2%) | 5 |
| Ultrasound Doppler | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Metabolism and nutrition disorders | ||||
| Dehydration | 3/3232 (0.1%) | 3 | 2/3260 (0.1%) | 2 |
| Diabetes mellitus | 2/3232 (0.1%) | 2 | 2/3260 (0.1%) | 2 |
| Diabetes mellitus inadequate control | 23/3232 (0.7%) | 25 | 33/3260 (1%) | 34 |
| Diabetes mellitus non-insulin-dependent | 3/3232 (0.1%) | 3 | 2/3260 (0.1%) | 2 |
| Diabetic foot | 3/3232 (0.1%) | 8 | 8/3260 (0.2%) | 8 |
| Diabetic ketoacidosis | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Electrolyte imbalance | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Gout | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Hyperkalaemia | 2/3232 (0.1%) | 2 | 3/3260 (0.1%) | 3 |
| Hypoglycaemia | 3/3232 (0.1%) | 3 | 4/3260 (0.1%) | 4 |
| Hypokalaemia | 2/3232 (0.1%) | 2 | 0/3260 (0%) | 0 |
| Hyponatraemia | 0/3232 (0%) | 0 | 2/3260 (0.1%) | 2 |
| Hypovolaemia | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Malnutrition | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Metabolic syndrome | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Arthritis | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Back pain | 0/3232 (0%) | 0 | 2/3260 (0.1%) | 2 |
| Dactylitis | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Gouty arthritis | 2/3232 (0.1%) | 2 | 2/3260 (0.1%) | 2 |
| Haemarthrosis | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Intervertebral disc degeneration | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Intervertebral disc protrusion | 6/3232 (0.2%) | 6 | 2/3260 (0.1%) | 2 |
| Monarthritis | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Musculoskeletal chest pain | 0/3232 (0%) | 0 | 5/3260 (0.2%) | 5 |
| Musculoskeletal pain | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Osteitis | 0/3232 (0%) | 0 | 3/3260 (0.1%) | 3 |
| Osteoarthritis | 3/3232 (0.1%) | 3 | 6/3260 (0.2%) | 6 |
| Osteochondrosis | 1/3232 (0%) | 1 | 1/3260 (0%) | 1 |
| Osteoporosis | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Osteoporotic fracture | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Polyarthritis | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Rheumatoid arthritis | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Rotator cuff syndrome | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Spinal osteoarthritis | 4/3232 (0.1%) | 4 | 1/3260 (0%) | 1 |
| Systemic sclerosis | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Tenosynovitis stenosans | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Basal cell carcinoma | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Benign biliary neoplasm | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Benign breast neoplasm | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Benign lung neoplasm | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Bladder cancer | 3/3232 (0.1%) | 3 | 2/3260 (0.1%) | 2 |
| Bladder papilloma | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Breast cancer | 2/3232 (0.1%) | 2 | 1/3260 (0%) | 1 |
| Breast cancer in situ | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Breast cancer metastatic | 1/3232 (0%) | 1 | 1/3260 (0%) | 1 |
| Breast cancer stage IV | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Bronchial carcinoma | 2/3232 (0.1%) | 2 | 0/3260 (0%) | 0 |
| Cervix carcinoma | 1/3232 (0%) | 1 | 2/3260 (0.1%) | 2 |
| Chronic lymphocytic leukaemia recurrent | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Chronic myeloid leukaemia | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Clear cell carcinoma of the kidney | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Colon cancer | 3/3232 (0.1%) | 3 | 4/3260 (0.1%) | 4 |
| Colon cancer metastatic | 1/3232 (0%) | 1 | 2/3260 (0.1%) | 2 |
| Diffuse large B-cell lymphoma | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Gallbladder cancer | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Gastric cancer | 4/3232 (0.1%) | 4 | 4/3260 (0.1%) | 4 |
| Hepatic cancer metastatic | 1/3232 (0%) | 1 | 1/3260 (0%) | 1 |
| Hepatic neoplasm | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Hepatic neoplasm malignant | 1/3232 (0%) | 1 | 1/3260 (0%) | 1 |
| Lung adenocarcinoma | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Lung cancer metastatic | 2/3232 (0.1%) | 2 | 1/3260 (0%) | 1 |
| Lung carcinoma cell type unspecified stage III | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Lung carcinoma cell type unspecified stage IV | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Lung neoplasm malignant | 5/3232 (0.2%) | 5 | 4/3260 (0.1%) | 4 |
| Malignant mediastinal neoplasm | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Malignant melanoma | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Meningioma | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Metastases to bone | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Metastases to central nervous system | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Metastases to liver | 1/3232 (0%) | 1 | 1/3260 (0%) | 1 |
| Metastases to lung | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Myelodysplastic syndrome | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Nasopharyngeal cancer | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Non-small cell lung cancer | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Oesophageal carcinoma | 2/3232 (0.1%) | 2 | 0/3260 (0%) | 0 |
| Oropharyngeal cancer stage unspecified | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Pancreatic carcinoma | 0/3232 (0%) | 0 | 2/3260 (0.1%) | 2 |
| Pancreatic carcinoma metastatic | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Papillary thyroid cancer | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Prostate cancer | 4/3232 (0.1%) | 4 | 5/3260 (0.2%) | 5 |
| Prostate cancer metastatic | 0/3232 (0%) | 0 | 2/3260 (0.1%) | 2 |
| Prostate cancer recurrent | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Prostatic adenoma | 3/3232 (0.1%) | 3 | 0/3260 (0%) | 0 |
| Rectal adenoma | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Rectal cancer | 4/3232 (0.1%) | 4 | 1/3260 (0%) | 1 |
| Rectal cancer metastatic | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Renal cancer metastatic | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Renal cell carcinoma stage unspecified | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Renal neoplasm | 3/3232 (0.1%) | 3 | 2/3260 (0.1%) | 2 |
| Salivary gland neoplasm | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Small intestine carcinoma | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Squamous cell carcinoma of skin | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Thyroid adenoma | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Tongue carcinoma stage IV | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Tongue neoplasm malignant stage unspecified | 2/3232 (0.1%) | 2 | 0/3260 (0%) | 0 |
| Uterine cancer | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Uterine leiomyoma | 2/3232 (0.1%) | 2 | 1/3260 (0%) | 1 |
| Nervous system disorders | ||||
| Brain stem haemorrhage | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Carotid artery occlusion | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Carotid artery stenosis | 5/3232 (0.2%) | 5 | 4/3260 (0.1%) | 4 |
| Cerebellar haemorrhage | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Cerebellar infarction | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Cerebral arteriosclerosis | 2/3232 (0.1%) | 2 | 3/3260 (0.1%) | 3 |
| Cerebral artery embolism | 1/3232 (0%) | 1 | 1/3260 (0%) | 1 |
| Cerebral haematoma | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Cerebral haemorrhage | 1/3232 (0%) | 1 | 3/3260 (0.1%) | 3 |
| Cerebral infarction | 7/3232 (0.2%) | 7 | 12/3260 (0.4%) | 13 |
| Cerebral ischaemia | 0/3232 (0%) | 0 | 3/3260 (0.1%) | 3 |
| Cerebrovascular accident | 14/3232 (0.4%) | 14 | 16/3260 (0.5%) | 17 |
| Cerebrovascular disorder | 1/3232 (0%) | 1 | 1/3260 (0%) | 1 |
| Cognitive disorder | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Coma | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Dementia | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Dementia Alzheimer's type | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Depressed level of consciousness | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Diabetic neuropathy | 2/3232 (0.1%) | 2 | 4/3260 (0.1%) | 4 |
| Dizziness | 0/3232 (0%) | 0 | 2/3260 (0.1%) | 2 |
| Embolic stroke | 1/3232 (0%) | 1 | 3/3260 (0.1%) | 3 |
| Encephalitis | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Encephalopathy | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Epilepsy | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Extrapyramidal disorder | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Facial palsy | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Grand mal convulsion | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Haemorrhagic stroke | 3/3232 (0.1%) | 3 | 4/3260 (0.1%) | 4 |
| Headache | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Hypertensive encephalopathy | 1/3232 (0%) | 1 | 2/3260 (0.1%) | 2 |
| Hypoglycaemic coma | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Hypoxic encephalopathy | 0/3232 (0%) | 0 | 2/3260 (0.1%) | 2 |
| Intracranial aneurysm | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Intracranial haematoma | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Ischaemic cerebral infarction | 2/3232 (0.1%) | 2 | 1/3260 (0%) | 1 |
| Ischaemic stroke | 34/3232 (1.1%) | 37 | 46/3260 (1.4%) | 48 |
| Lacunar infarction | 1/3232 (0%) | 1 | 3/3260 (0.1%) | 3 |
| Loss of consciousness | 1/3232 (0%) | 1 | 4/3260 (0.1%) | 4 |
| Metabolic encephalopathy | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Migraine with aura | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Neuropathy peripheral | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Paraesthesia | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Polyneuropathy | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Sciatica | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Spinal cord haemorrhage | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Subarachnoid haemorrhage | 2/3232 (0.1%) | 2 | 0/3260 (0%) | 0 |
| Syncope | 12/3232 (0.4%) | 12 | 20/3260 (0.6%) | 21 |
| Syncope vasovagal | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Tarsal tunnel syndrome | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Transient ischaemic attack | 11/3232 (0.3%) | 12 | 12/3260 (0.4%) | 12 |
| Vascular dementia | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Vascular encephalopathy | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Vertebrobasilar insufficiency | 3/3232 (0.1%) | 3 | 3/3260 (0.1%) | 4 |
| Pregnancy, puerperium and perinatal conditions | ||||
| Pregnancy | 1/3232 (0%) | 1 | 1/3260 (0%) | 1 |
| Psychiatric disorders | ||||
| Affective disorder | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Aggression | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Alcoholism | 3/3232 (0.1%) | 3 | 2/3260 (0.1%) | 2 |
| Anxiety | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Anxiety disorder | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Completed suicide | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Delirium | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Depression | 3/3232 (0.1%) | 3 | 1/3260 (0%) | 1 |
| Disturbance in social behaviour | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Schizophreniform disorder | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Suicide attempt | 2/3232 (0.1%) | 2 | 0/3260 (0%) | 0 |
| Renal and urinary disorders | ||||
| Acute prerenal failure | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Anuria | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Calculus ureteric | 1/3232 (0%) | 1 | 1/3260 (0%) | 1 |
| Calculus urinary | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Diabetic nephropathy | 1/3232 (0%) | 1 | 1/3260 (0%) | 2 |
| Glomerulonephritis chronic | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Nephrolithiasis | 2/3232 (0.1%) | 2 | 1/3260 (0%) | 1 |
| Nephropathy toxic | 1/3232 (0%) | 1 | 1/3260 (0%) | 1 |
| Nephrotic syndrome | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Polyuria | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Renal artery stenosis | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Renal colic | 2/3232 (0.1%) | 2 | 0/3260 (0%) | 0 |
| Renal failure | 14/3232 (0.4%) | 14 | 14/3260 (0.4%) | 14 |
| Renal failure acute | 11/3232 (0.3%) | 13 | 7/3260 (0.2%) | 7 |
| Renal failure chronic | 2/3232 (0.1%) | 2 | 4/3260 (0.1%) | 4 |
| Renal impairment | 1/3232 (0%) | 1 | 1/3260 (0%) | 1 |
| Stress incontinence | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Urethral stenosis | 0/3232 (0%) | 0 | 1/3260 (0%) | 2 |
| Urinary retention | 1/3232 (0%) | 2 | 0/3260 (0%) | 0 |
| Reproductive system and breast disorders | ||||
| Benign prostatic hyperplasia | 5/3232 (0.2%) | 5 | 2/3260 (0.1%) | 2 |
| Endometrial hyperplasia | 1/3232 (0%) | 1 | 1/3260 (0%) | 1 |
| Metrorrhagia | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Ovarian cyst | 0/3232 (0%) | 0 | 2/3260 (0.1%) | 2 |
| Phimosis | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Postmenopausal haemorrhage | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Uterine haemorrhage | 0/3232 (0%) | 0 | 2/3260 (0.1%) | 2 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Acute pulmonary oedema | 20/3232 (0.6%) | 25 | 25/3260 (0.8%) | 31 |
| Acute respiratory distress syndrome | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Acute respiratory failure | 2/3232 (0.1%) | 2 | 3/3260 (0.1%) | 3 |
| Alveolitis allergic | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Asthma | 2/3232 (0.1%) | 3 | 4/3260 (0.1%) | 12 |
| Asthmatic crisis | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Bronchial hyperactivity | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Bronchopneumopathy | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Bronchospasm | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Chronic obstructive pulmonary disease | 35/3232 (1.1%) | 53 | 33/3260 (1%) | 50 |
| Chronic respiratory failure | 2/3232 (0.1%) | 2 | 0/3260 (0%) | 0 |
| Diaphragmatic hernia | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Dyspnoea | 1/3232 (0%) | 1 | 3/3260 (0.1%) | 4 |
| Dyspnoea at rest | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Dyspnoea exacerbated | 1/3232 (0%) | 1 | 2/3260 (0.1%) | 2 |
| Emphysema | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Epistaxis | 2/3232 (0.1%) | 2 | 1/3260 (0%) | 1 |
| Haemopneumothorax | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Haemoptysis | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Hydrothorax | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Interstitial lung disease | 3/3232 (0.1%) | 3 | 2/3260 (0.1%) | 2 |
| Nasal cyst | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Non-cardiogenic pulmonary oedema | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Pleural effusion | 1/3232 (0%) | 1 | 3/3260 (0.1%) | 3 |
| Pleurisy | 3/3232 (0.1%) | 3 | 2/3260 (0.1%) | 2 |
| Pneumonia aspiration | 1/3232 (0%) | 1 | 1/3260 (0%) | 1 |
| Pneumonitis | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Pneumothorax | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Pulmonary embolism | 8/3232 (0.2%) | 9 | 23/3260 (0.7%) | 24 |
| Pulmonary fibrosis | 1/3232 (0%) | 1 | 1/3260 (0%) | 1 |
| Pulmonary hypertension | 0/3232 (0%) | 0 | 2/3260 (0.1%) | 2 |
| Pulmonary infarction | 0/3232 (0%) | 0 | 2/3260 (0.1%) | 3 |
| Respiratory arrest | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Respiratory failure | 5/3232 (0.2%) | 5 | 5/3260 (0.2%) | 5 |
| Sleep apnoea syndrome | 4/3232 (0.1%) | 4 | 4/3260 (0.1%) | 4 |
| Status asthmaticus | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Skin and subcutaneous tissue disorders | ||||
| Cutaneous lupus erythematosus | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Decubitus ulcer | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Dermatitis atopic | 0/3232 (0%) | 0 | 2/3260 (0.1%) | 2 |
| Dry gangrene | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Eczema | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Pruritus | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Psoriasis | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Skin ulcer | 1/3232 (0%) | 1 | 3/3260 (0.1%) | 3 |
| Subcutaneous emphysema | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Social circumstances | ||||
| Social stay hospitalisation | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Surgical and medical procedures | ||||
| Alcohol detoxification | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Arrhythmia prophylaxis | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Arterial bypass operation | 1/3232 (0%) | 1 | 1/3260 (0%) | 1 |
| Cardiac ablation | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Cardiac aneurysm repair | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Cardiac pacemaker insertion | 4/3232 (0.1%) | 4 | 0/3260 (0%) | 0 |
| Cardiac rehabilitation therapy | 7/3232 (0.2%) | 9 | 7/3260 (0.2%) | 10 |
| Cardiac resynchronisation therapy | 20/3232 (0.6%) | 21 | 29/3260 (0.9%) | 30 |
| Carotid endarterectomy | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Cataract operation | 1/3232 (0%) | 2 | 2/3260 (0.1%) | 2 |
| Cholecystectomy | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Coronary angioplasty | 1/3232 (0%) | 1 | 1/3260 (0%) | 1 |
| Coronary arterial stent insertion | 1/3232 (0%) | 1 | 5/3260 (0.2%) | 5 |
| Coronary artery surgery | 12/3232 (0.4%) | 12 | 5/3260 (0.2%) | 5 |
| Coronary revascularisation | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Diabetes mellitus management | 1/3232 (0%) | 1 | 1/3260 (0%) | 1 |
| Ear operation | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Eventration procedure | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Gastric banding | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Heart transplant | 1/3232 (0%) | 1 | 4/3260 (0.1%) | 4 |
| Hip arthroplasty | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Implantable defibrillator insertion | 17/3232 (0.5%) | 17 | 21/3260 (0.6%) | 21 |
| Implantable defibrillator replacement | 0/3232 (0%) | 0 | 4/3260 (0.1%) | 4 |
| Incisional hernia repair | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Inguinal hernia repair | 0/3232 (0%) | 0 | 2/3260 (0.1%) | 2 |
| Knee arthroplasty | 1/3232 (0%) | 1 | 2/3260 (0.1%) | 2 |
| Knee operation | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Mitral valve replacement | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Obesity surgery | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Percutaneous coronary intervention | 5/3232 (0.2%) | 5 | 2/3260 (0.1%) | 2 |
| Physiotherapy | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Rehabilitation therapy | 2/3232 (0.1%) | 2 | 2/3260 (0.1%) | 2 |
| Renal tumour excision | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Tooth extraction | 2/3232 (0.1%) | 2 | 0/3260 (0%) | 0 |
| Transurethral prostatectomy | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Ureteral stent removal | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Weight loss diet | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Vascular disorders | ||||
| Aortic aneurysm | 1/3232 (0%) | 1 | 3/3260 (0.1%) | 4 |
| Aortic aneurysm rupture | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Aortic dissection | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Aortic stenosis | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Arterial thrombosis limb | 3/3232 (0.1%) | 3 | 4/3260 (0.1%) | 4 |
| Arteriosclerosis | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Arteriosclerosis obliterans | 3/3232 (0.1%) | 3 | 3/3260 (0.1%) | 4 |
| Bleeding varicose vein | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Blood pressure inadequately controlled | 17/3232 (0.5%) | 19 | 13/3260 (0.4%) | 13 |
| Deep vein thrombosis | 1/3232 (0%) | 1 | 7/3260 (0.2%) | 7 |
| Diabetic macroangiopathy | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Diabetic vascular disorder | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Extremity necrosis | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Femoral artery aneurysm | 1/3232 (0%) | 3 | 0/3260 (0%) | 0 |
| Femoral artery dissection | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Femoral artery occlusion | 2/3232 (0.1%) | 2 | 1/3260 (0%) | 1 |
| Haematoma | 1/3232 (0%) | 1 | 1/3260 (0%) | 1 |
| Hypertension | 1/3232 (0%) | 1 | 1/3260 (0%) | 1 |
| Hypertensive crisis | 5/3232 (0.2%) | 5 | 5/3260 (0.2%) | 5 |
| Hypertensive emergency | 2/3232 (0.1%) | 3 | 0/3260 (0%) | 0 |
| Hypotension | 3/3232 (0.1%) | 3 | 5/3260 (0.2%) | 5 |
| Iliac artery embolism | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Iliac artery occlusion | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Iliac artery thrombosis | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Intermittent claudication | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Lymphoedema | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Orthostatic hypotension | 4/3232 (0.1%) | 4 | 2/3260 (0.1%) | 2 |
| Peripheral arterial occlusive disease | 15/3232 (0.5%) | 15 | 15/3260 (0.5%) | 18 |
| Peripheral artery aneurysm | 1/3232 (0%) | 1 | 1/3260 (0%) | 1 |
| Peripheral embolism | 3/3232 (0.1%) | 4 | 1/3260 (0%) | 1 |
| Peripheral ischaemia | 1/3232 (0%) | 1 | 5/3260 (0.2%) | 7 |
| Peripheral vascular disorder | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Subclavian artery stenosis | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Thrombophlebitis | 1/3232 (0%) | 1 | 0/3260 (0%) | 0 |
| Thrombophlebitis superficial | 0/3232 (0%) | 0 | 2/3260 (0.1%) | 2 |
| Thrombosis | 0/3232 (0%) | 0 | 1/3260 (0%) | 1 |
| Varicose vein | 1/3232 (0%) | 1 | 1/3260 (0%) | 1 |
| Venous thrombosis limb | 2/3232 (0.1%) | 2 | 0/3260 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||
| Ivabradine | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2062/3232 (63.8%) | 2020/3260 (62%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 91/3232 (2.8%) | 93 | 92/3260 (2.8%) | 96 |
| Cardiac disorders | ||||
| Angina pectoris | 85/3232 (2.6%) | 97 | 93/3260 (2.9%) | 109 |
| Atrial fibrillation | 161/3232 (5%) | 176 | 123/3260 (3.8%) | 138 |
| Atrioventricular block first degree | 35/3232 (1.1%) | 38 | 36/3260 (1.1%) | 42 |
| Bradycardia | 134/3232 (4.1%) | 142 | 26/3260 (0.8%) | 30 |
| Cardiac failure | 289/3232 (8.9%) | 337 | 299/3260 (9.2%) | 369 |
| Sinus tachycardia | 40/3232 (1.2%) | 45 | 102/3260 (3.1%) | 115 |
| Supraventricular extrasystoles | 39/3232 (1.2%) | 41 | 49/3260 (1.5%) | 50 |
| Ventricular extrasystoles | 129/3232 (4%) | 140 | 131/3260 (4%) | 137 |
| Ventricular tachycardia | 34/3232 (1.1%) | 37 | 26/3260 (0.8%) | 28 |
| Eye disorders | ||||
| Phosphenes | 89/3232 (2.8%) | 95 | 16/3260 (0.5%) | 18 |
| Gastrointestinal disorders | ||||
| Gastritis | 34/3232 (1.1%) | 34 | 36/3260 (1.1%) | 36 |
| Infections and infestations | ||||
| Bronchitis | 38/3232 (1.2%) | 44 | 34/3260 (1%) | 40 |
| Bronchitis acute | 59/3232 (1.8%) | 64 | 68/3260 (2.1%) | 79 |
| Influenza | 66/3232 (2%) | 74 | 68/3260 (2.1%) | 76 |
| Nasopharyngitis | 66/3232 (2%) | 70 | 70/3260 (2.1%) | 85 |
| Pneumonia | 56/3232 (1.7%) | 60 | 69/3260 (2.1%) | 78 |
| Respiratory tract infection | 39/3232 (1.2%) | 40 | 25/3260 (0.8%) | 28 |
| Respiratory tract infection viral | 30/3232 (0.9%) | 33 | 34/3260 (1%) | 36 |
| Upper respiratory tract infection | 33/3232 (1%) | 35 | 52/3260 (1.6%) | 55 |
| Urinary tract infection | 24/3232 (0.7%) | 24 | 37/3260 (1.1%) | 40 |
| Injury, poisoning and procedural complications | ||||
| Fall | 36/3232 (1.1%) | 40 | 42/3260 (1.3%) | 47 |
| Investigations | ||||
| Blood creatinine increased | 55/3232 (1.7%) | 58 | 47/3260 (1.4%) | 49 |
| Heart rate decreased | 178/3232 (5.5%) | 193 | 45/3260 (1.4%) | 46 |
| Transaminases increased | 46/3232 (1.4%) | 48 | 42/3260 (1.3%) | 42 |
| Metabolism and nutrition disorders | ||||
| Diabetes mellitus | 32/3232 (1%) | 32 | 35/3260 (1.1%) | 35 |
| Diabetes mellitus inadequate control | 116/3232 (3.6%) | 125 | 115/3260 (3.5%) | 125 |
| Hypercholesterolaemia | 33/3232 (1%) | 33 | 34/3260 (1%) | 34 |
| Hyperkalaemia | 27/3232 (0.8%) | 29 | 53/3260 (1.6%) | 56 |
| Hyperuricaemia | 47/3232 (1.5%) | 47 | 52/3260 (1.6%) | 52 |
| Musculoskeletal and connective tissue disorders | ||||
| Osteoarthritis | 24/3232 (0.7%) | 24 | 40/3260 (1.2%) | 42 |
| Nervous system disorders | ||||
| Dizziness | 55/3232 (1.7%) | 62 | 45/3260 (1.4%) | 50 |
| Headache | 43/3232 (1.3%) | 45 | 58/3260 (1.8%) | 67 |
| Renal and urinary disorders | ||||
| Renal failure | 50/3232 (1.5%) | 53 | 69/3260 (2.1%) | 71 |
| Renal failure chronic | 27/3232 (0.8%) | 28 | 45/3260 (1.4%) | 45 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Chronic obstructive pulmonary disease | 37/3232 (1.1%) | 42 | 55/3260 (1.7%) | 68 |
| Cough | 42/3232 (1.3%) | 44 | 44/3260 (1.3%) | 44 |
| Vascular disorders | ||||
| Blood pressure inadequately controlled | 216/3232 (6.7%) | 259 | 188/3260 (5.8%) | 215 |
| Hypotension | 59/3232 (1.8%) | 62 | 82/3260 (2.5%) | 91 |
Limitations/Caveats
The section Other Adverse Events (Not including serious) has been completed by the sponsor to include only the Non Serious Adverse Events emergent on treatment during the study.
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review publication and/or communication related to the study results and can require changes. In case of a patent application, the sponsor can delay its authorization for publication or communication of the study results until the date of international registration of the patent.
Results Point of Contact
| Name/Title | Therapeutic Innovation Pole |
|---|---|
| Organization | Institut de Recherches Internationales Servier (I.R.I.S.) |
| Phone | +33155724366 |
| clinicaltrials@servier.com |
Responsible Party:
Institut de Recherches Internationales Servier
ClinicalTrials.gov Identifier:
NCT02441218
Other Study ID Numbers:
- CL3-16257-063
- 2006-000708-18
First Posted:
May 12, 2015
Last Update Posted:
Jan 3, 2020
Last Verified:
Jan 1, 2020