Ivabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a randomised, double-blind, placebo-controlled trial.

By K. Fox, Ian Ford, G. Steg, M. Tendera, R. Ferrari. The Lancet, 2008

1,013 citations recorded by the source corpus.

BACKGROUND Ivabradine specifically inhibits the I(f) current in the sinoatrial node to lower heart rate, without affecting other aspects of cardiac function. We aimed to test whether lowering the heart rate with ivabradine reduces cardiovascular death and morbidity in patients with coronary artery disease and left-ventricular systolic dysfunction. METHODS Between December, 2004, and December, 2006, we screened 12 473 patients at 781 centres in 33 countries. We enrolled 10 917 eligible patients who had coronary artery disease and a left-ventricular ejection fraction of less than 40% in a randomised, double-blind, placebo-controlled, parallel-group trial. 5479 patients received 5 mg ivabradine, with the intention of increasing to the target dose of 7.5 mg twice a day, and 5438 received matched placebo in addition to appropriate cardiovascular medication. The primary endpoint was a composite of cardiovascular death, admission to hospital for acute myocardial infarction, and admission to hospital for new onset or worsening heart failure. We analysed patients by intention to treat. The study is registered with ClinicalTrials.gov, number NCT00143507. FINDINGS Mean heart rate at baseline was 71.6 (SD 9.9) beats per minute (bpm). Median follow-up was 19 months (IQR 16-24). Ivabradine reduced heart rate by 6 bpm (SE 0.2) at 12 months, corrected for placebo. Most (87%) patients were receiving beta blockers in addition to study drugs, and no safety concerns were identified. Ivabradine did not affect the primary composite endpoint (hazard ratio 1.00, 95% CI 0.91-1.1, p=0.94). 1233 (22.5%) patients in the ivabradine group had serious adverse events, compared with 1239 (22.8%) controls (p=0.70). In a prespecified subgroup of patients with heart rate of 70 bpm or greater, ivabradine treatment did not affect the primary composite outcome (hazard ratio 0.91, 95% CI 0.81-1.04, p=0.17), cardiovascular death, or admission to hospital for new-onset or worsening heart failure. However, it did reduce secondary endpoints: admission to hospital for fatal and non-fatal myocardial infarction (0.64, 95% CI 0.49-0.84, p=0.001) and coronary revascularisation (0.70, 95% CI 0.52-0.93, p=0.016). INTERPRETATION Reduction in heart rate with ivabradine does not improve cardiac outcomes in all patients with stable coronary artery disease and left-ventricular systolic dysfunction, but could be used to reduce the incidence of coronary artery disease outcomes in a subgroup of patients who have heart rates of 70 bpm or greater.

Subfields: Cardiology and Cardiovascular Medicine

View Paper: https://www.semanticscholar.org/paper/f845e921ff33cb7205774a37a945873b1bae6b2c

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cardiology and Cardiovascular Medicine

Citations in the corpus

ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012 (2012, background): “Although ivabradine did not reduce the primary outcome of cardiovascular death, myocardial infarction, or HF hospitalization, it was well tolerated.(122)”
2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. (2017, background): “IIa B-R Ivabradine can be beneficial to reduce HF hospitalization for patients with symptomatic (NYHA class II-III) stable chronic HF rEF (LVEF ≤35%) who are receiving GDEM*, including a beta blocker at maximum tolerated dose, and who are in sinus rhythm with a heart rate of 70 bpm or greater at res”
European Guidelines on Cardiovascular Disease Prevention in Clinical Practice (Version 2012) (2012, positive): “and reduced left ventricular function (either coronary artery disease or heart failure), trials of pure heart rate reduction have shown benefit.(64,65) There is not enough evidence, at present, to recommend a target heart rate.”
CONSORT 2010 explanation and elaboration: updated guidelines for reporting parallel group randomised trials. (2012, background): “The environment in which the trial is conducted may differ considerably from the setting in which the trial’s results are later used to guide practice and policy [94,99].”
CONSORT 2010 Explanation and Elaboration: updated guidelines for reporting parallel group randomised trials (2010, background): “’’[115] ExplanationdFor scientific and ethical reasons, the sample size for a trial needs to be planned carefully, with a balance between medical and statistical considerations.”