The ivabradine journey

Large body of epidemiological evidence showed strong correlation between heart rate and total or cardiovascular (CV) mortality. These data do not, however, clarify the role of increased heart rate in CV disease, basically because they do not distinguish whether increased heart rate is a risk marker or a risk factor. The distinction is relevant for therapeutic value, since if it is the cause-or one of the causes-of the disease and its progression; its reduction corresponds to a prognostic benefit. Ivabradine, a selective heart rate-lowering agent, provides an opportunity to assess the effects of lowering heart rate without directly altering other aspects of cardiac function. Experimental and clinical data with ivabradine illustrate important therapeutic benefits resulted from this therapy-improvement in coronary perfusion (myocardial perfusion, collateral coronary flow) and cardiac efficiency (improvement in LV function, reversing of remodelling). For this reason, consideration of the 'Ivabradine journey' is particularly relevant, not only to establish its therapeutic role in treating different manifestations of the CV continuum but also to establish the role of heart rate in this continuum. Results of SHIFT trial demonstrated that an increased heart rate actively contributes to the outcome as a risk factor, and selective heart rate reduction with ivabradine provides a prognostic benefit. In patients with angina, heart rate is a major determinant of ischaemia and myocardial perfusion time; therefore, heart rate reduction is an integral part of antianginal therapy. In setting of stable coronary artery disease without LVSD, the results of SIGNIfY helped to determine that an elevated heart rate is a risk marker and its reduction does not improve the outcome while improving the symptoms of angina.