Evaluation of the SIGNIFY trial

Area of Science:

• Cardiology
• Pharmacology

Background:

• Heart rate reduction is a potential therapeutic strategy for coronary artery disease (CAD).
• The If inhibitor ivabradine targets heart rate reduction.

Purpose of the Study:

• To evaluate the cardiovascular benefits and safety of ivabradine in patients with stable CAD and heart rate ≥ 70 bpm.

Main Methods:

• The Study Assessing the Morbidity-Mortality Benefits of the If Inhibitor, Ivabradine, in patients with coronary artery disease (SIGNIFY) trial enrolled 19,102 patients.
• Patients received ivabradine (5-10 mg bid) or placebo, in addition to standard treatment.
• The primary endpoint was the composite of cardiovascular death or nonfatal myocardial infarction over a mean follow-up of 2.3 years.

Main Results:

• No significant difference in the primary endpoint was observed between the ivabradine and placebo groups (6.8% vs 6.4%, p=NS).
• In patients with angina (class II or higher), ivabradine significantly increased the primary endpoint incidence (7.6% vs 6.5%, p < 0.02).
• Increased incidence of bradycardia, atrial fibrillation, and Q-T prolongation was noted with ivabradine.

Conclusions:

• The SIGNIFY trial does not support the routine clinical use of ivabradine for improving cardiovascular outcomes in patients with stable coronary artery disease.
• Ivabradine may increase risks in specific patient subgroups, particularly those with angina.