A step further with ivabradine: SIGNIfY (Study assessInG the morbidity–mortality beNefits of the If inhibitor ivabradine in patients with coronarY artery disease)
1 Chair of Cardiology, University of Ferrara, Arcispedale S. Anna Hospital, C.rso Giovecca 203, 44100 Ferrara, Italy
2 Cardiovascular Research Centre, Salvatore Maugeri Foundation, IRCCS, Ferrara, Italy
* Corresponding author. Tel: +39 0532 202143, Fax: +39 0532 241885, E-mail address: fri{at}unife.it
Recently, it has been recognized that elevated resting heart rate (HR) is an independent risk factor for all-cause and cardiovascular mortality, not only in the general population, but also in patients with cardiovascular disease. Ivabradine is a specific inhibitor of the If current in the sinoatrial node providing a pure HR reduction without modification of other cardiovascular parameters. Treatment with ivabradine therefore provides an opportunity to assess the effects of lowering HR without directly altering other aspects of cardiac function. Ivabradine has been proven to effectively prevent myocardial ischaemia and treat symptoms in patients with chronic stable angina pectoris. The BEAUTIfUL trial sheds new light on the role of HR control in cardiovascular disease and shows that ivabradine in patients with HR above 70 b.p.m. prevents coronary outcomes. These are particularly important data because they have been obtained on top of the best possible preventive therapy, including β-blockers. BEAUTIfUL has also led to a series of stimulating hypotheses that constitute the rationale for another trial called SIGNIfY, which will enrol patients with coronary artery disease (CAD) and normal left ventricular function with a resting HR of 
70 b.p.m. The primary endpoint will take into consideration only CAD outcomes, i.e. CV mortality and hospitalization for myocardial infarction. So SIGNIfY will be a logical extension of BEAUTIfUL.
Key Words: Heart rate • Coronary artery disease • Ivabradine