Problem CAD & LVF < 40%
Format Double-blinded multi-center RCT
Treatment Ivabradine
Control Placebo
Population 10,917 eligible patients
Inclusion criteria Patients eligible for inclusion were of either sex, aged 55 years or older (or 18 years or older if diabetic), with coronary artery disease (documented by previous myocardial infarction, previous percutaneous or surgical coronary revascularisation, or angiographic evidence that one or more major coronary arteries had narrowed by 50% or more), left-ventricular ejection fraction of less than 40%, and end-diastolic short-axis internal dimension of greater than 56 mm by echocardiography. Patients had to be in sinus rhythm, with resting heart rate of 60 beats per minute (bpm) or greater. Any angina or symptoms of heart failure should have been stable for at least 3 months and patients should have received appropriate conventional cardiovascular medication at stable doses for at least 1 month.
Exclusion criteria All patients who had myocardial infarction or coronary revascularisation within the previous 6 months; stroke or cerebral transient ischaemic attack within the previous 3 months; an implanted pacemaker, cardioverter, or defibrillator; valvular disease likely to need surgery within 3 years; sick sinus syndrome; sinoatrial block; congenital long QT; complete atrioventricular block; severe or uncontrolled hypertension; or existing symptoms of severe heart failure (New York Heart Association [NYHA] class IV). We also excluded all patients who were receiving treatment with strong CYP P450 3A4 inhibitors.
Follow-up Median 19 months
Primary endpoint Composite of cardiovascular death, admission to hospital for acute myocardial infarction, and admission to hospital for new onset or worsening heart failure
Secondary endpoint(s) Secondary endpoints were (1) all-cause mortality; (2) cardiac death (death from myocardial infarction or heart failure, or death related to a cardiac procedure); (3) cardiovascular death (defi ned as cardiac death, death from a vascular procedure, presumed arrhythmic death, stroke death, other vascular death, or sudden death of unknown cause) or admission to hospital for new-onset or worsening heart failure; (4) the composite of admission to hospital for fatal and non-fatal acute myocardial infarction or unstable angina; (5) coronary revascularisation; (6) cardiovascular death; (7) admission to hospital for heart failure; and (8) admission to hospital for myocardial infarction. Prespecified events were adjudicated by a central endpoint validation committee, and an independent data monitoring committee was responsible for the oversight of the study
Details .
Brief summary: Ivabradine beneficial in angina 7 HR > 70; see SHIFT
PAPER: Ivabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a randomised, double-blind, placebo-controlled trial.
Date 6 Sep 2011
Journal Lancet. 2008 Sep 6;372(9641):807-16. Epub 2008 Aug 29.
Information N.B. Patients on optimal treatment (b-blocker, statin, ACEi/ARB & antiplatelets)
-87% on beta-blockers

No significant benefit in composite endpoint (CV death, MI or CCF admission) in either:
-All patients
-Pre-specified subgroup with HR > 70
--However, this group did have reduction in admission for fatal & non-fatal MI
PAPER: Heart rate as a prognostic risk factor in patients with coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a subgroup analysis of a randomised controlled trial.
Date 6 Sep 2008
Journal Lancet. 2008 Sep 6;372(9641):817-21. Epub 2008 Aug 29.
Information Subgroup analysis of placebo group
Adjustments made for baseline characteristics

Patients with HR > 70 showed increased:
-Risk for cardiovascular death
-Admission to hospital for heart failure
-Admission to hospital for myocardial infarction
-Coronary revascularisation
Risks increased for all every 5 bpm
PAPER: Relationship between ivabradine treatment and cardiovascular outcomes in patients with stable coronary artery disease and left ventricular systolic dysfunction with limiting angina
Date 30 Oct 2009
Journal Eur Heart J. 2009 Oct;30(19):2337-45. Epub 2009 Aug 31.
Information Subgroup analysis on patients with angina as limiting symptom at baseline (13.8%)
-Ivabradine associated with 24% reduction in primary endpoint
--(CV mortality, MI or CCF hospitalisation)

In those with angina & HR > 70
-73% reduction in hospitalization for MI
-59% reduction in coronary revascularization