Role of the Funny Current Inhibitor Ivabradine in Cardiac Pharmacotherapy: A Systematic Review

Abstract

The pharmacology, pharmacokinetics, efficacy and safety of ivabradine are reviewed. Ivabradine is an oral medication that directly and selectively inhibits the hyperpolarization-activated cyclic-nucleotide gated funny (If) current in the sinoatrial node resulting in heart rate reduction. It has a plasma elimination half-life of 6 hours and is administered twice daily. Ivabradine is extensively metabolized by cytochrome P450 3A4, and its metabolism is affected by inducers and inhibitors of the 3A4 enzyme. Studies in patients with heart failure indicate that ivabradine improves surrogate markers such as exercise tolerance. The results of (1) phase III trial demonstrated ivabradine significantly reduced heart failure hospitalizations but had no effect on mortality. Ivabradine has been extensively evaluated for coronary artery disease wherein (2) large trials was shown to have no mortality benefit. Ivabradine has been associated with improved symptoms in stable chronic angina pectoris. Ivabradine has been evaluated for other cardiovascular conditions including tachycardias of various natures, arrhythmia prevention postcardiac surgery, in acute coronary syndrome, and for heart rate control during coronary computed tomography angiogram. The most common adverse events reported in clinical trials were bradycardia, new-onset atrial fibrillation, and phosphenes. Ivabradine, a novel cardiac medication, has been studied in numerous cardiac conditions. It is only currently approved in the United States to reduce hospitalizations for systolic heart failure. The role of this medication in other conditions has not been fully elucidated.

New Novel Treatment Approaches for Heart Failure With Reduced Ejection Fraction

“…Coadministration with strong CYP3A4 inhibitors is contraindicated and use with moderate CYP3A4 inhibitors or concurrent use with CYP3A4 inducers should ideally be avoided. [46][47][48][49] Ivabradine's FDA approval was largely based on SHIFT trial, where 6558 eligible adult patients were assigned to 2 treatment arms (3268 ivabradine and 3290 placebo) based on the following eligibility criteria: NYHA class II to IV HF, LVEF of less than or equal to 35%, resting heart rate 70 beats/min or higher, and admittance to a hospital for worsening HF within 12 months before study entry. In addition to their background treatment appropriate to their systolic dysfunction that generally included a beta-blocker, patients initially received 5 mg twice daily of the study drug or placebo.…”

“…Coadministration with strong CYP3A4 inhibitors is contraindicated and use with moderate CYP3A4 inhibitors or concurrent use with CYP3A4 inducers should ideally be avoided. 46 –49…”

Clinical Study of The Early Application of Lvabradine For Acute Anterior Myocardial Infarction Patients After PCI With Early Heart Failure To Observe Cardiac Function And Prognosis

“…Because it binds to the If channel of sinoatrial node cells and speci cally inhibits the If current, ivabradine reduces depolarization speed and heart rate. Ivabradine also has no direct effect on myocardial contraction, ventricular repolarization or intracardiac conduction time 2 .…”

Stability Indicating Method Development and Validation of Carvedilol and Ivabradine in Bulk and its Formulation by Reverse Phase High Performance Liquid Chromatography Method

“…3 Ivabradine is a cardiac medication chemically it is named as 3-[[3-[(7S)-3,4-dimethoxy-7-bicyclo [4.2.0] octa-1,3,5-trienyl] methyl-methylamino] propyl]-7,8-dimethoxy-2,5-dihydro-1H-3-benzazepin-4-one (Figure 2). 7,8 it reduces heart rate and RESEARCH ARTICLE use in treating heart failure patients. Ivabradine is selectively inhibited, if (funny channel), located in a sinoatrial node which controls the diastolic depolarization.…”