A reduction in the heart rate has been thought to be beneficial in
coronary artery disease. The study assessing the morbidity-mortality Benefits of the If Inhibitor,
Ivabradine, in patients with
coronary artery disease (SIGNIFY) tested this hypothesis. It specifically evaluated the effects of
ivabradine, administered at the dosage of 5 - 10 mg/bid in addition to current
drug treatment, on cardiovascular outcome in 19102 patients with heart rate ≥ 70 bpm in normal sinus rhythm and stable
coronary artery disease without
heart failure. The primary endpoint of the trial, whose follow-up averaged for 2.3 years, was a composite of death from cardiovascular causes or nonfatal
myocardial infarction whereas the secondary endpoint was represented by the primary endpoint plus total mortality. The incidence of the primary endpoint was at the study end similar in the
ivabradine-treated and in the placebo-treated group (6.8 vs 6.4%, p = NS). Superimposable was also the incidence of death for cardiovascular events and for nonfatal
myocardial infarction. However, in the 12049 patients with angina class II or higher
ivabradine significantly increased the incidence of primary endpoint as compared to placebo (7.6 vs 6.5%, p < 0.02). This was associated with a significantly greater incidence of
bradycardia,
atrial fibrillation and Q-T prolongation. Taken together the results of the SIGNIFY do not support the clinical benefits of
ivabradine in patients with stable
coronary artery disease.