Ivabradine: The Hope for a Good Treatment of Ischemic Heart Disease

G.      Riccioni

Abstract

Chronic stable angina pectoris (CSAP) is the most common manifestation of coronary artery disease (CAD). Angina pectoris occurs as a result of an imbalance between myocardial perfusion and the demands of the myocardium. Elevated heart rate (HR) is an important pathophysiological variable that increases myocardial oxygen demand, and also limits tissue perfusion by reducing the duration of diastole during which most myocardial perfusion occurs. Elevated resting HR represents a significant predictor of all-cause and cardiovascular mortality in the general population and patients with cardiovascular disease (CVD) because it assists the progression of CVD through the development of atherosclerosis, plaque destabilization, and initiation of arrhythmias. Since β-blockers have been found to reduce HR, therefore, they are currently viewed as the first line therapy for CSAP and are associated with an improved prognosis after acute myocardial infarction (AMI) or congestive heart failure (CHF). The classical treatments for HR reduction have shown negative aspects, such as β-blockers therapy which exerts negative effects on regional myocardial blood flow and function when HR reduction is eliminated by atrial pacing. Calcium channel antagonists functionally antagonize coronary vasoconstriction mediated through α-adrenoreceptors, and are thus devoid of this undesired effect, but the compounds are nevertheless negative inotrope. Ivabradine (IVA), a pure HR lowering drug, reduces the demand of myocardial oxygen during exercise, contributes to the restoration of oxygen balance and is therefore benefitial in chronic CVD. No relevant negative effects have been observed on cardiac conduction, contractility, relaxation, repolarization or blood pressure (BP). Beneficial effects of IVA have been noticedin CSAP and CHF, with optimal tolerability profile due to selective interaction with I_f channel of sino atrial node cells. More recently, IVA has been highly recommended to be used in patients with CAD in association with β-blockers. This review highlights the importance of IVA in the treatment of ischemic heart disease.

Keywords: Angina, coronary artery disease, funny current, HCN channels, heart rate, ivabradine, sino atrial node.

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