Evaluation of the SIGNIFY trial

Guido Grassi

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)1861-1864
Number of pages4
JournalExpert Opinion on Pharmacotherapy
Issue number12
Publication statusPublished - Aug 1 2015


  • atrial fibrillation
  • coronary artery disease
  • heart rate
  • ivabradine
  • J curve

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology


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