Trial Outcomes & Findings for The BEAUTIFUL Study: Effects of Ivabradine in Patients With Stable Coronary Artery Disease and Left Ventricular Systolic Dysfunction (NCT NCT00143507)

Last Updated: 2018-04-12

Results Overview

First event among cardiovascular death, hospitalisation for acute myocardial infarction (fatal or not), or hospitalisation for new onset or worsening heart failure (fatal or not).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

10917 participants

Primary outcome timeframe

From the date of randomisation to the date of the first occurrence of the first event, up to 3 years.

Results posted on

2018-04-12

Participant Flow

Eligible participants were men and women, with documented history of coronary artery disease, associated with left ventricular systolic dysfunction. Angina and/or heart failure symptoms should have been stable for ≥ 3 months, with optimal conventional cardiovascular medication on appropriate stable doses for at least 1 month.

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.

Participant milestones

Participant milestones
Measure	Ivabradine Patients received ivabradine at starting dose of 5 mg twice daily, with a target dose, if HR tolerance criteria were met after two weeks (at the D15 visit), of 7.5 mg twice daily.	Placebo Patients received placebo twice daily.
Overall Study STARTED	5479	5438
Overall Study COMPLETED	4792	4786
Overall Study NOT COMPLETED	687	652

Reasons for withdrawal

Reasons for withdrawal
Measure	Ivabradine Patients received ivabradine at starting dose of 5 mg twice daily, with a target dose, if HR tolerance criteria were met after two weeks (at the D15 visit), of 7.5 mg twice daily.	Placebo Patients received placebo twice daily.
Overall Study Death	572	547
Overall Study Withdrawal by Subject	114	102
Overall Study Lost to Follow-up	1	0
Overall Study Withdrawn by sponsor's decision	0	3

Baseline Characteristics

The BEAUTIFUL Study: Effects of Ivabradine in Patients With Stable Coronary Artery Disease and Left Ventricular Systolic Dysfunction

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ivabradine n=5479 Participants Patients received ivabradine at starting dose of 5 mg twice daily, with a target dose, if HR tolerance criteria were met after two weeks (at the D15 visit), of 7.5 mg twice daily.	Placebo n=5438 Participants Patients received placebo twice daily.	Total n=10917 Participants Total of all reporting groups
Age, Continuous	65.3 years STANDARD_DEVIATION 8.5 • n=5 Participants	65 years STANDARD_DEVIATION 8.4 • n=7 Participants	65.2 years STANDARD_DEVIATION 8.5 • n=5 Participants
Sex: Female, Male Female	939 Participants n=5 Participants	931 Participants n=7 Participants	1870 Participants n=5 Participants
Sex: Female, Male Male	4540 Participants n=5 Participants	4507 Participants n=7 Participants	9047 Participants n=5 Participants
Beta-blocker intake Yes	4749 participants n=5 Participants	4738 participants n=7 Participants	9487 participants n=5 Participants
Beta-blocker intake No	730 participants n=5 Participants	700 participants n=7 Participants	1430 participants n=5 Participants

PRIMARY outcome

Timeframe: From the date of randomisation to the date of the first occurrence of the first event, up to 3 years.

First event among cardiovascular death, hospitalisation for acute myocardial infarction (fatal or not), or hospitalisation for new onset or worsening heart failure (fatal or not).

Outcome measures

Outcome measures
Measure	Ivabradine n=5479 Participants Patients received ivabradine at starting dose of 5 mg twice daily, with a target dose, if HR tolerance criteria were met after two weeks (at the D15 visit), of 7.5 mg twice daily.	Placebo n=5438 Participants Patients received placebo twice daily.
Primary Composite Endpoint	844 participants	832 participants

SECONDARY outcome

Timeframe: From the date of randomisation to death, up to 3 years.

Cardiovascular death including sudden death of unknown cause

Outcome measures

Outcome measures
Measure	Ivabradine n=5479 Participants Patients received ivabradine at starting dose of 5 mg twice daily, with a target dose, if HR tolerance criteria were met after two weeks (at the D15 visit), of 7.5 mg twice daily.	Placebo n=5438 Participants Patients received placebo twice daily.
Cardiovascular Death	469 participants	435 participants

SECONDARY outcome

Timeframe: From the date of randomisation to the date of first occurrence of the event, up to 3 years.

Outcome measures

Outcome measures
Measure	Ivabradine n=5479 Participants Patients received ivabradine at starting dose of 5 mg twice daily, with a target dose, if HR tolerance criteria were met after two weeks (at the D15 visit), of 7.5 mg twice daily.	Placebo n=5438 Participants Patients received placebo twice daily.
Hospitalisation for Acute Myocardial Infarction	199 Participants	226 Participants

SECONDARY outcome

Timeframe: From the date of randomisation to the date of first occurrence of the event, up to 3 years.

Outcome measures

Outcome measures
Measure	Ivabradine n=5479 Participants Patients received ivabradine at starting dose of 5 mg twice daily, with a target dose, if HR tolerance criteria were met after two weeks (at the D15 visit), of 7.5 mg twice daily.	Placebo n=5438 Participants Patients received placebo twice daily.
Hospitalisation for New Onset or Worsening Heart Failure	426 participants	427 participants

SECONDARY outcome

Timeframe: From the date of randomisation to death, up to 3 years.

Outcome measures

Outcome measures
Measure	Ivabradine n=5479 Participants Patients received ivabradine at starting dose of 5 mg twice daily, with a target dose, if HR tolerance criteria were met after two weeks (at the D15 visit), of 7.5 mg twice daily.	Placebo n=5438 Participants Patients received placebo twice daily.
All-cause of Mortality	572 participants	547 participants

SECONDARY outcome

Timeframe: From the date of randomisation to death, up to 3 years.

Death due to heart failure, acute myocardial infarction or cardiac procedure

Outcome measures

Outcome measures
Measure	Ivabradine n=5479 Participants Patients received ivabradine at starting dose of 5 mg twice daily, with a target dose, if HR tolerance criteria were met after two weeks (at the D15 visit), of 7.5 mg twice daily.	Placebo n=5438 Participants Patients received placebo twice daily.
Coronary Artery Disease Death	136 participants	151 participants

SECONDARY outcome

Timeframe: From the date of randomisation to the date of first occurrence of the event, up to 3 years.

Outcome measures

Outcome measures
Measure	Ivabradine n=5479 Participants Patients received ivabradine at starting dose of 5 mg twice daily, with a target dose, if HR tolerance criteria were met after two weeks (at the D15 visit), of 7.5 mg twice daily.	Placebo n=5438 Participants Patients received placebo twice daily.
Hospitalisation for Coronary Revascularisation	155 participants	186 participants

SECONDARY outcome

Timeframe: From the date of randomisation to the date of first occurrence of the event, up to 3 years.

Outcome measures

Outcome measures
Measure	Ivabradine n=5479 Participants Patients received ivabradine at starting dose of 5 mg twice daily, with a target dose, if HR tolerance criteria were met after two weeks (at the D15 visit), of 7.5 mg twice daily.	Placebo n=5438 Participants Patients received placebo twice daily.
Hospitalisation for Unstable Angina	114 participants	105 participants

SECONDARY outcome

Timeframe: From the date of randomisation to the date of first occurrence of the first event, up to 3 years.

Outcome measures

Outcome measures
Measure	Ivabradine n=5479 Participants Patients received ivabradine at starting dose of 5 mg twice daily, with a target dose, if HR tolerance criteria were met after two weeks (at the D15 visit), of 7.5 mg twice daily.	Placebo n=5438 Participants Patients received placebo twice daily.
Hospitalisation for Acute Coronary Syndrome (Unstable Angina or Acute Myocardial Infarction)	303 participants	317 participants

SECONDARY outcome

Timeframe: From the date of randomisation to the date of first occurrence of the first event, up to 3 years.

Outcome measures

Outcome measures
Measure	Ivabradine n=5479 Participants Patients received ivabradine at starting dose of 5 mg twice daily, with a target dose, if HR tolerance criteria were met after two weeks (at the D15 visit), of 7.5 mg twice daily.	Placebo n=5438 Participants Patients received placebo twice daily.
Hospitalisation for Acute Coronary Syndrome, or Coronary Revascularisation	364 participants	401 participants

SECONDARY outcome

Timeframe: From the date of randomisation to the date of first occurrence of the first event, up to 3 years.

Outcome measures

Outcome measures
Measure	Ivabradine n=5479 Participants Patients received ivabradine at starting dose of 5 mg twice daily, with a target dose, if HR tolerance criteria were met after two weeks (at the D15 visit), of 7.5 mg twice daily.	Placebo n=5438 Participants Patients received placebo twice daily.
Hospitalisation for Acute Coronary Syndrome, New Onset or Worsening Heart Failure or Coronary Revascularisation	681 participants	704 participants

SECONDARY outcome

Timeframe: From the date of randomisation to the date of first occurrence of the first event, up to 3 years.

Outcome measures

Outcome measures
Measure	Ivabradine n=5479 Participants Patients received ivabradine at starting dose of 5 mg twice daily, with a target dose, if HR tolerance criteria were met after two weeks (at the D15 visit), of 7.5 mg twice daily.	Placebo n=5438 Participants Patients received placebo twice daily.
Cardiovascular Death, or Hospitalisation for New Onset or Worsening Heart Failure	757 participants	723 participants

SECONDARY outcome

Timeframe: From the date of randomisation to the date of the first occurrence of the first event, up to 3 years.

Outcome measures

Outcome measures
Measure	Ivabradine n=5479 Participants Patients received ivabradine at starting dose of 5 mg twice daily, with a target dose, if HR tolerance criteria were met after two weeks (at the D15 visit), of 7.5 mg twice daily.	Placebo n=5438 Participants Patients received placebo twice daily.
Cardiovascular Death, or Hospitalisation for Acute Myocardial Infarction	606 participants	593 participants

Adverse Events

Ivabradine

Serious events: 1625 serious events

Other events: 2570 other events

Deaths: 0 deaths

Placebo

Serious events: 1770 serious events

Other events: 2221 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Therapeutic Innovation Pole

Institut de Recherches Internationales Servier (I.R.I.S.)

Phone: +33155724366

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Ivabradine n=5477 participants at risk Patients received ivabradine at starting dose of 5 mg twice daily, with a target dose, if HR tolerance criteria were met after two weeks (at the D15 visit), of 7.5 mg twice daily.	Placebo n=5430 participants at risk Patients received placebo twice daily.
Eye disorders Glaucoma	0.04% 2/5477 • Number of events 2 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	0.04% 2/5430 • Number of events 2 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).
Eye disorders Eye haemorrhage	0.02% 1/5477 • Number of events 1 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	0.00% 0/5430 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).
Blood and lymphatic system disorders Anaemia	0.15% 8/5477 • Number of events 8 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	0.17% 9/5430 • Number of events 11 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).
Blood and lymphatic system disorders Aplastic anaemia	0.02% 1/5477 • Number of events 1 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	0.00% 0/5430 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).
Blood and lymphatic system disorders Hypochromic anaemia	0.02% 1/5477 • Number of events 1 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	0.00% 0/5430 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).
Blood and lymphatic system disorders Idiopathic thrombocytopenic purpura	0.00% 0/5477 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	0.04% 2/5430 • Number of events 2 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).
Blood and lymphatic system disorders Iron deficiency anaemia	0.00% 0/5477 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	0.07% 4/5430 • Number of events 4 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).
Blood and lymphatic system disorders Leukaemoid reaction	0.02% 1/5477 • Number of events 1 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	0.00% 0/5430 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).
Blood and lymphatic system disorders Lymphadenopathy	0.00% 0/5477 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	0.02% 1/5430 • Number of events 1 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).
Blood and lymphatic system disorders Normochromic normocytic anaemia	0.02% 1/5477 • Number of events 1 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	0.00% 0/5430 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).
Blood and lymphatic system disorders Thrombocytopenia	0.04% 2/5477 • Number of events 2 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	0.02% 1/5430 • Number of events 1 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).
Cardiac disorders Accelerated idioventricular rhythm	0.02% 1/5477 • Number of events 2 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	0.00% 0/5430 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).
Cardiac disorders Acute coronary syndrome	0.29% 16/5477 • Number of events 18 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	0.39% 21/5430 • Number of events 22 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).
Cardiac disorders Acute left ventricular failure	0.35% 19/5477 • Number of events 22 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	0.33% 18/5430 • Number of events 18 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).
Cardiac disorders Acute myocardial infarction	1.5% 82/5477 • Number of events 85 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	1.6% 88/5430 • Number of events 96 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).
Cardiac disorders Angina pectoris	0.68% 37/5477 • Number of events 38 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	1.2% 66/5430 • Number of events 73 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).
Cardiac disorders Angina unstable	2.8% 153/5477 • Number of events 182 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	3.6% 197/5430 • Number of events 223 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).
Cardiac disorders Aortic valve disease mixed	0.00% 0/5477 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	0.02% 1/5430 • Number of events 1 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).
Cardiac disorders Aortic valve incompetence	0.00% 0/5477 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	0.02% 1/5430 • Number of events 1 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).
Cardiac disorders Aortic valve stenosis	0.04% 2/5477 • Number of events 2 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	0.02% 1/5430 • Number of events 1 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).
Cardiac disorders Arrhythmia supraventricular	0.00% 0/5477 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	0.02% 1/5430 • Number of events 1 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).
Cardiac disorders Atrial fibrillation	2.3% 127/5477 • Number of events 145 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	2.5% 134/5430 • Number of events 162 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).
Cardiac disorders Atrial flutter	0.64% 35/5477 • Number of events 38 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	0.52% 28/5430 • Number of events 30 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).
Cardiac disorders Atrial tachycardia	0.02% 1/5477 • Number of events 1 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	0.09% 5/5430 • Number of events 5 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).
Cardiac disorders Atrioventricular block complete	0.18% 10/5477 • Number of events 10 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	0.22% 12/5430 • Number of events 12 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).
Cardiac disorders Atrioventricular block second degree	0.15% 8/5477 • Number of events 8 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	0.13% 7/5430 • Number of events 7 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).
Cardiac disorders Bradycardia	0.40% 22/5477 • Number of events 22 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	0.11% 6/5430 • Number of events 6 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).
Cardiac disorders Cardiac arrest	0.04% 2/5477 • Number of events 2 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	0.04% 2/5430 • Number of events 2 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).
Cardiac disorders Cardiac asthma	0.09% 5/5477 • Number of events 5 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	0.07% 4/5430 • Number of events 5 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).
Cardiac disorders Cardiac failure	7.4% 405/5477 • Number of events 517 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	8.1% 438/5430 • Number of events 584 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).
Cardiac disorders Cardiac tamponade	0.02% 1/5477 • Number of events 1 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	0.02% 1/5430 • Number of events 1 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).
Cardiac disorders Cardiogenic shock	0.00% 0/5477 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	0.13% 7/5430 • Number of events 7 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).
Cardiac disorders Cardiopulmonary failure	0.04% 2/5477 • Number of events 2 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	0.00% 0/5430 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).
Cardiac disorders Congestive cardiomyopathy	0.00% 0/5477 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	0.02% 1/5430 • Number of events 1 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).
Cardiac disorders Coronary artery disease	0.24% 13/5477 • Number of events 15 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	0.35% 19/5430 • Number of events 19 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).
Cardiac disorders Coronary artery insufficiency	0.00% 0/5477 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	0.06% 3/5430 • Number of events 3 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).
Cardiac disorders Coronary artery occlusion	0.00% 0/5477 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	0.04% 2/5430 • Number of events 2 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).
Cardiac disorders Coronary artery stenosis	0.02% 1/5477 • Number of events 1 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	0.00% 0/5430 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).
Cardiac disorders Coronary artery thrombosis	0.00% 0/5477 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	0.02% 1/5430 • Number of events 1 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).
Cardiac disorders Extrasystoles	0.04% 2/5477 • Number of events 2 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	0.02% 1/5430 • Number of events 1 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).

Other adverse events
Measure	Ivabradine n=5477 participants at risk Patients received ivabradine at starting dose of 5 mg twice daily, with a target dose, if HR tolerance criteria were met after two weeks (at the D15 visit), of 7.5 mg twice daily.	Placebo n=5430 participants at risk Patients received placebo twice daily.
Blood and lymphatic system disorders Anaemia	1.1% 61/5477 • Number of events 62 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	1.1% 60/5430 • Number of events 61 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).
Cardiac disorders Angina pectoris	1.8% 100/5477 • Number of events 108 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	1.8% 98/5430 • Number of events 110 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).
Cardiac disorders Atrial fibrillation	3.1% 172/5477 • Number of events 203 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	2.7% 148/5430 • Number of events 167 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).
Cardiac disorders Bradycardia	3.4% 185/5477 • Number of events 189 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	0.92% 50/5430 • Number of events 51 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).
Cardiac disorders Cardiac failure	3.2% 176/5477 • Number of events 198 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	3.5% 188/5430 • Number of events 210 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).
Cardiac disorders Ventricular extrasystoles	1.8% 99/5477 • Number of events 102 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	1.7% 95/5430 • Number of events 100 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).
Eye disorders Phosphenes	3.8% 206/5477 • Number of events 219 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	0.85% 46/5430 • Number of events 49 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).
General disorders Chest pain	0.86% 47/5477 • Number of events 50 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	1.1% 59/5430 • Number of events 67 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).
General disorders Fatigue	1.1% 59/5477 • Number of events 62 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	1.0% 56/5430 • Number of events 60 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).
General disorders Oedema peripheral	0.75% 41/5477 • Number of events 44 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	1.0% 56/5430 • Number of events 56 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).
Infections and infestations Bronchitis	1.3% 71/5477 • Number of events 83 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	1.5% 80/5430 • Number of events 100 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).
Infections and infestations Bronchitis acute	0.89% 49/5477 • Number of events 53 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	1.1% 61/5430 • Number of events 64 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).
Infections and infestations Influenza	1.2% 65/5477 • Number of events 74 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	1.3% 73/5430 • Number of events 78 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).
Infections and infestations Nasopharyngitis	1.5% 84/5477 • Number of events 89 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	1.6% 87/5430 • Number of events 98 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).
Infections and infestations Pneumonia	1.0% 56/5477 • Number of events 58 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	0.96% 52/5430 • Number of events 57 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).
Investigations Blood cholesterol increased	1.0% 56/5477 • Number of events 57 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	1.4% 75/5430 • Number of events 77 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).
Investigations Blood creatinine increased	1.0% 57/5477 • Number of events 61 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	0.98% 53/5430 • Number of events 56 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).
Investigations Blood triglycerides increased	1.1% 59/5477 • Number of events 59 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	1.1% 62/5430 • Number of events 62 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).
Investigations Heart rate decreased	3.0% 164/5477 • Number of events 164 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	0.63% 34/5430 • Number of events 36 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).
Metabolism and nutrition disorders Diabetes mellitus	1.2% 68/5477 • Number of events 68 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	0.99% 54/5430 • Number of events 55 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).
Metabolism and nutrition disorders Diabetes mellitus inadequate control	2.7% 150/5477 • Number of events 155 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	3.1% 171/5430 • Number of events 192 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).
Metabolism and nutrition disorders Gout	0.80% 44/5477 • Number of events 49 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	1.0% 57/5430 • Number of events 63 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).
Metabolism and nutrition disorders Hyperkalaemia	1.1% 60/5477 • Number of events 66 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	1.2% 64/5430 • Number of events 66 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).
Nervous system disorders Dizziness	1.9% 103/5477 • Number of events 109 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	1.5% 81/5430 • Number of events 85 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).
Nervous system disorders Headache	1.0% 55/5477 • Number of events 60 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	0.98% 53/5430 • Number of events 60 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).
Renal and urinary disorders Renal insufficiency	1.0% 56/5477 • Number of events 60 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	1.1% 61/5430 • Number of events 62 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).
Vascular disorders Blood pressure inadequately controlled	3.3% 181/5477 • Number of events 203 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	3.3% 177/5430 • Number of events 191 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).
Vascular disorders Hypotension	0.84% 46/5477 • Number of events 50 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).	1.3% 70/5430 • Number of events 72 • From randomization to death, up to 3 years The Randomised Set consisted of 10 917 patients (5479 patients in the ivabradine group and 5438 patients in the placebo group). The Safety Set consisted of 10 907 patients: 10 randomised patients were excluded from the Safety Set because they did not take any study drug (2 patients in the ivabradine group and 8 patients in the placebo group).