Selective and Specific If Inhibition in Cardiovascular Disease

The data presented and discussed in this monograph support the concept of heart rate reduction as a valuable therapeutic option for reducing morbidity and mortality in a wide range of cardiovascular disease. Clinical evidence has been accumulating for many years to suggest a link between heart rate and mortality in patients with coronary artery disease, as well as in the general population. Epidemiologic data, particularly from the Framingham study, have also indicated a strong link between sudden cardiac death and sustained elevated heart rate, raising the issue that slow heart rate per se might exert an antifibrillatory action. In this respect, an elevated heart rate can be considered as an independent risk factor for cardiovascular mortality. There is also evidence to suggest that a sustained elevated heart rate may play a direct role in the pathogenesis of coronary atherosclerosis. It is widely accepted that lowering heart rate can reduce the risk of cardiovascular events and increase life expectancy.The heart rate-lowering effects of beta blockers have been correlated with reduced cardiovascular and total mortality in post-myocardial infarction and heart failure patients. In theory, a highly specific heart rate-lowering agent should have the same beneficial effects with respect to reduced risk and mortality and may avoid some of the drawbacks associated with beta blocker therapy. The objectives of current therapies are to increase coronary blood flow and decrease myocardial oxygen demand. Heart rate is a critical determinant of myocardial oxygen consumption and a reduction in heart rate usually leads to a reduction in myocardial oxygen consumption. Coronary blood flow can be improved by a slower heart rate due to an increase in diastolic perfusion time during the heart cycle. The role of specific heart rate-lowering agents needs to be explored in this context...