Ivabradine: Evidence and current role in cardiovascular diseases and other emerging indications

Abstract

Increased heart rate (HR) is associated with deleterious effects on several disease conditions. Chronic heart failure (CHF) is one of the cardiovascular diseases with recurrent hospitalization burden and an ongoing drain on health-care expenditure. Despite advancement in medicine, management of CHF remains a challenge to health-care providers. Ivabradine selectively and specifically inhibits the pacemaker I(f) ionic current which reduces the cardiac pacemaker activity. The main effect of ivabradine therapy is the substantial lowering of HR. It does not influence intracardiac conduction, contractility, or ventricular repolarization. As shown in numerous clinical studies, ivabradine improves clinical outcomes and quality of life and reduces the risk of death from heart failure (HF) or other cardiovascular causes. Recently updated HF guidelines recommend ivabradine as a class II indication for reduction of HF hospitalizations. Based on the principle of benefits of reduced HR, the ivabradine in patients with ischemic heart disease, sepsis, and multiple organ dysfunction syndrome has also been studied. It can also be a useful agent for HR reduction in patients with contraindications to use beta-blockers or those who cannot tolerate them. In this review, we provide an overview of efficacy and safety of ivabradine and its combination with currently recommended pharmacological therapy in different conditions.

Ivabradine-Management of Heart Failure (Systematic Review)

“…Ivabradine is the sole available HCN (hyperpolarization-activated cyclic nucleotidegated) inhibitor. It slows HR by reduction of the If current-regulated diastolic depolarization in the sinoatrial node, increasing diastolic time without altering the action potential duration or causing negative inotropy [7].…”

“…Caution is required in patients with creatinine clearance below 15 ml/min. Ivabradine is contraindicated in patients with severe liver damage [7].…”

“…Ivabradine as an If modulator was developed for coronary artery disease and heart failure treatment. Currently, various regulatory agencies recommend the use of ivabradine in patients with HR (heart rate) of ≥70 bpm [7][8][9]. This active substance selectively inhibits the ionic current If, which modulates pacemaker activity in the sino-atrial node, providing selective heart rate reduction [10].…”

Ivabradine in Postural Orthostatic Tachycardia Syndrome: A Review of the Literature

“…In addition, it prolongs diastolic perfusion time and improves coronary flow velocity reserves. These physiological changes result into an increased ischemic threshold and an improvement in angina [33]. Ivabradine reduces HR almost linearly with an oral dose ranging from 0.5 to 24 mg.…”

Evaluation of ivabradine plus beta-blocker versus beta-blocker alone in addition to standard care in reducing hospitalization and major adverse cardiovascular event in patients with chronic heart failure: a prospective observational study in tertiary care hospital in central India

“…Adequate control of heart rate decreases the incidence of MACE and the frequency of hospitalization [7]. Ivabradine is added for patients who had inadequate control of heart rate with a maximum dose of beta-blocker, or who have reached a maximum tolerable dose, or who are intolerant to beta-blocker, to decrease the incidence of both hospitalization and adverse cardiac outcomes [8]. Due to minimal studies on ivabradine in chronic heart failure patients in the Indian population, we have done this prospective, observational study to assess the clinical effectiveness of ivabradine plus beta-blocker versus betablocker alone in addition to standard care in reducing hospitalization and major adverse cardiovascular event in patients with chronic heart failure.…”