Ivabradine in the treatment of ischemic heart disease – results of the BEAUTIFUL study

Authors: J. Hradec
Authors‘ workplace: III. interní klinika 1. lékařské fakulty UK a VFN, Praha
Published in: Kardiol Rev Int Med 2010, 12(1): 0


The aim of the BEAUTIFUL clinical trail was to evaluate whether lowering of the heart rate (HR) with the specific sinoatrial node If channels inhibitor ivabradine in patients with stabilized ischemic heart disease (IHD) and left ventricular systolic dysfunction leads to a reduction in cardiovascular mortality and morbidity. The study placebo arm served for testing the hypothesis that elevated resting HR is a marker of subsequent cardiovascular mortality and morbidity. The study involved 10 970 patients with documented IHD and left ventricular ejection fraction of < 0.40, who were randomized to take either ivabradine or placebo. The primary clinical endpoint was the sum of cardiovascular deaths, hospitalisations due to myocardial infarction and hospitalizations due to cardiac failure. The patients were followed up for a median of 19 months. The mean basal HR of the patients entering the study was 71.6/ min. Patients in the placebo arm with resting HR ≥ 70/ min had, in comparison to those with resting HR < 70/ min, higher risk of cardiovascular death (by 34%; p=0.0041), hospitalizations due to cardiac failure (by 53%; p < 0.001), hospitalizations due to myocardial infarction (by 46 %; p = 0.0066) and coronary revascularization (by 38%; p = 0.037). Administration of ivabradine did not affect the incidence of the composite clinical endpoint (HR = 1.0; n.s.). Treatment with ivabradine in a pre‑defined subgroup of patients with basal resting HR ≥ 70/ min significantly reduced the number of post myocardial infarction hospitalizations (HR = 0.94; p = 0.001) and the need for coronary revascularization (HR = 0.70; p = 0.016). Post hoc analysis published a year later showed that ivabradine significantly reduced incidence of primary clinical endpoint by 24% and the number of hospitalizations for myocardial infarction by 42% in patients who suffered from limiting angina at baseline. The majority of patients included in the study (87%) took beta‑blockers. Administration of ivabradine was safe and well tolerated. HR reduction with ivabradine in patients with IHD and left ventricular systolic dysfunction did not reduce the risk of cardiovascular events. Elevated resting HR (≥ 70/ min) identifies the patients with significantly increased risk of cardiovascular events. Reduction of HR with ivabradine in these patients had a positive effect on patient prognosis. Ivabradine also reduced the incidence of cardiovascular events in patients suffering from limiting angina at baseline. The results suggested that the positive effects of ivabradine are multiplied in patient with higher HR and co‑ morbid angina.

Key words:
angina pectoris – ivabradine – BEAUTIFUL clinical trial – heart rate reduction – cardiovascular mortality – cardiovascular morbidity


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