Abstract
Heart rate (HR) is a precisely regulated variable, which plays a critical role in health and disease. Elevated resting HR is a significant predictor of all-cause and cardiovascular mortality in the general population and patients with cardiovascular disease (CVD). β-blocking drugs exert negative effects on regional myocardial blood flow and function when HR reduction is eliminated by atrial pacing; calcium channel antagonists (CCAs) functionally antagonize coronary vasoconstriction mediated through α-adreno-receptors and are thus devoid of this undesired effect, but the compounds are nevertheless negative inotropes. From these observations derives the necessity to find alternative, more selective drugs to reduce HR through inhibition of specific electrical current (If). Ivabradine (IVA) is a novel specific HR-lowering agent that acts in sinus atrial node (SAN) cells by selectively inhibiting the pacemaker If current in a dose-dependent manner by slowing the diastolic depolarization slope of SAN cells, and by reducing HR at rest during exercise in humans. Coronary artery diseases (CAD) represent the most common cause of death in middle–aged and older adults in European Countries. Most ischemic episodes are triggered by an increase in HR, that induces an imbalance between myocardial oxygen delivery and consumption. IVA, a selective and specific inhibitor of the If current which reduced HR without adverse hemodynamic effects, has clearly and unequivocally demonstrated its efficacy in the treatment of chronic stable angina pectoris (CSAP) and myocardial ischemia with optimal tolerability profile due to selective interaction with If channels. The aim of this review is to point out the usefulness of IVA in the treatment of ischemic heart disease.
Highlights
Angina is a chest discomfort caused by myocardial ischemia without necrosis, and is further qualified by its precipitating factors, time course to relief, and clinical characteristics, such as radiation and quality
This is referred to as an imbalance between myocardial oxygen supply and demand, but it should be clear that substrate supply, utilization, and enzymatic activities, along with other variables involved in intermediary metabolism and mitochondrial function, play a major role in the pathogenesis of myocardial ischemia in angina, acute coronary syndromes, and during reperfusion ischemic injury [3]
Specific interaction studies in healthy volunteers and patients have shown that the combination of IVA with the Heart rate (HR) reducing agents diltiazem or verapamil resulted in an increase in IVA exposure (2 to 3 fold increase in area under the curve (AUC)) and an additional HR reduction of 5 bpm [48]
Summary
Angina is a chest discomfort caused by myocardial ischemia without necrosis, and is further qualified by its precipitating factors, time course to relief, and clinical characteristics, such as radiation and quality. A primary factor in CSAP results from myocardial ischemia, which is caused by an imbalance between myocardial O2 requirements and myocardial O2 supply [1] This is referred to as an imbalance between myocardial oxygen supply and demand, but it should be clear that substrate supply, utilization, and enzymatic activities, along with other variables involved in intermediary metabolism and mitochondrial function, play a major role in the pathogenesis of myocardial ischemia in angina, acute coronary syndromes, and during reperfusion ischemic injury [3]. Pathological vasomotor control was found in CSAP patients with angiographically normal coronary arteries in which the chest pain is due to a reduction of endothelium-dependent vasodilation of resistance arteries. A careful clinical history, the implementation of appropriate diagnostic tests and a rational use of anti-anginal drugs often ensure the successful control of the patient's symptoms [4]
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