Use Of Ivabradine Research Articles

Clinical trials update from the European Society of Cardiology Meeting 2010: SHIFT, PEARL‐HF, STAR‐heart, and HEBE‐III

This article provides information and a commentary on key trials relevant to the pathophysiology, prevention, and treatment of heart failure (HF) presented at the annual meeting of the European Society of Cardiology held in Stockholm in 2010. Unpublished reports should be considered as preliminary, since analyses may change in the final publication. The SHIFT study supports the use of ivabradine in patients with HF due to left ventricular systolic dysfunction and resting sinus rhythm rate ≥70 b.p.m. despite treatment with beta-blockers or where beta-blockers are contra-indicated. Results from PEARL-HF suggest that the potassium binding polymer RLY5016 may be useful for both prevention and treatment of hyperkalaemia in HF patients with or without concomitant chronic kidney disease. The STAR-heart study provides encouraging observational data about the potential for intracoronary stem cell transplantation in patients with HF. Results from HEBE-III showed no effect of erythropoietin on ejection fraction measured 6 weeks post-MI; although there were fewer cardiovascular events in patients assigned to erythropoietin, the study was too small to provide conclusive evidence of effect.

Impact of ‘‘Off-Label’’ Use of Ivabradine on Exercise Capacity, Gas Exchange, Functional Class, Quality of Life, and Neurohormonal Modulation in Patients With Ischemic Chronic Heart Failure

epidemiologic studies indicate that elevated heart rate (HR) is an independent risk factor for mortality and morbidity in patients (pts) with chronic heart failure (CHF). Clinical trials with β-blockers suggest that HR reduction is an important mechanism of their benefit in pts with stable CHF. Pharmacologic inhibition of the I(f) current now provides the opportunity of pure HR reduction. The purpose of this study was to evaluate the impact of ''Off-Label'' use of ivabradine on exercise capacity, gas exchange, functional class, quality of life, and neurohormonal modulation in pts with ischemic CHF. between January 2008 and June 2008, a graded maximal exercise test with respiratory gas analysis and an endurance test with constant workload corresponding to 85% of the peak VO(2) at the baseline and after 3 months were performed, and at the same times, N-terminal probrain natriuretic peptide (NT-proBNP) levels were also measured, in 60 pts (45 M, 15 F, mean age 52.7 ± 5.3 years), with stable ischemic CHF, New York Heart Association (NYHA) functional classes II (n = 35)-III (n = 25), with left ventricular ejection fraction (LVEF) ≤ 40%, randomized to a ''off-label'' ivabradine use (n = 30) and a control group (n = 30). the exercise capacity increased from 14.8 ± 2.5 to 28.2 ± 3.5 min (P < .0001) and the peak oxygen consumption tended to improve from 13.5 ± 1.3 to 17.9 ± 2.4 mL/kg per minute (P < .0001) in ivabradine group. Oxygen consumption at the anaerobic threshold (AT) increased from 11.9 ± 1.4 to 15.3 ± 1.4 mL/kg per minute (P < .0001). NTproBNP levels decreased from 2356 ± 2113 pg/mL to 1434 ± 1273 pg/mL (P = .045). No significant differences were found in control group at 3 months. The positive ivabradine effects were also associated with an improvement in the NYHA functional class and quality of life. the ''Off-Label'' use of ivabradine significantly improves the exercise capacity, gas exchange, functional heart failure class, quality of life, and neurohormonal modulation in pts with ischemic CHF.

Use of ivabradine in catecholamine-induced tachycardia after high-risk cardiac surgery

Use of ivabradine in catecholamine-induced tachycardia after high-risk cardiac surgery

Ivabradine to Treat Inappropriate Sinus Tachycardia after the Fast Pathway Ablation in a Patient with Severe Pectus Excavatum

We present the case of a 49-year-old woman with atrioventricular nodal re-entrant tachycardia and a severe pectus excavatum. The patient underwent an electrophysiological study and fast pathway ablation. Fast pathway ablation was not done on purpose but accidentally, likely due to the abnormal position of the heart in the chest cavity in this patient suffering from severe pectus excavatum. Some hours after the ablation, the patient developed inappropriate sinus tachycardia (IST), complaining of dyspnea and fatigue. IST has been described as a complication of fast pathway ablation in 10% of the cases. In our case it was not possible to treat IST with beta-blockers due to an important lowering of the blood pressure. Digitalis, given as second choice, was not successful. Ivabradine-the specific sinus node If current inhibitors-was used to successfully lower the heart rate with immediate relief of symptoms. A 24-hour Holter, 10 days later, showed a complete control of the heart rate without any episode of IST. The patient was completely symptom free and able to undertake her normal daily activities without any discomfort. Our case confirms the potential use of ivabradine for indications other than coronary artery disease.

Ivabradine Use in Refractory Unstable Angina: A Case Report

In this report, we describe the clinical results of ivabradine use in a patient with a serious form of unstable angina. For this patient, it was proposed that no other therapeutic, pharmacologic or surgical, option was available. The patient is a 75-year-old woman who presented with repeated episodes of retrosternal chest pain. She notably had a history of type II diabetes mellitus treated by insulin for several years and complicated by diabetic macro-angiopathy. ECG tracings recorded during these episodes showed abnormalities of the lateral repolarization phase of ischaemic nature. There was no measured increase in cardiac enzymes. She was transferred to our CCU with a diagnosis of unstable angina. In our CCU, the patient was treated with nitrates, metoprolol, aspirin, clopidogrel and atorvastatin at maximal sustainable doses. Following persistent clinical-instrumental instability, she was subjected to coronary angiography. This study revealed severe multi-vessel coronary artery disease not amenable to surgery or angioplasty revascularization. In addition to the therapy already provided, a beta-blocker (metoprolol 50 mgx2/die) and diltiazem (30 mgx2/die) were added despite their potentially dangerous and adverse chronotropic effects. Despite this treatment, the patients heart rate remained high (between 80 and 100 beats/min). This heart rate appeared to be the main driving cause of her anginal symptoms. At this point, the use of ivabradine seemed the only option, even though use would be off-label compared to current indications for the drugs use. We started with a low dose of 2.5 mg/b.i.d. and titrated up to 5 mg b.i.d. As we titrated, we witnessed a gradual reduction in heart rate. A consequent stabilization of her clinical pattern progressed into an almost unexpected asymptomatic state. After about a week of clinical observation, the patient recovered. After three months, she remains asymptomatic.

BEAUTIfUL-Studie – Analyse der Studienergebnisse

The results of the BEAUTIfUL-Study presented at the ESC meeting in Munich last year showed the following:

Ivabradine: Beyond heart rate control

Chronic stable angina pectoris (CSAP) usually occurs in patients with coronary artery disease (CAD) that affects one or more large epicardial arteries. It results when myocardial perfusion is insufficient to meet cardiac metabolic demand. Elevated heart rate (HR) is an important factor in the development of myocardial ischemia and angina pectoris. The pharmacologic agents most commonly administered in the treatment of CSAP are beta-blockers and calcium channel blockers (CCBs). However, the use of beta-blockers is limited by poor compliance related to contraindications and comorbidities, especially in elderly patients. Ivabradine is a new selective HR-lowering agent that selectively inhibits the pacemaker current I (f) in the sinus atrial node. In several randomized controlled trials, ivabradine 5-10 mg twice daily has demonstrated equivalent anti-ischemic and anti-anginal activity to beta-blockers and CCBs, with a good safety and tolerability profile. Although ivabradine has been shown not to improve cardiac outcomes in patients with stable CAD and left ventricular systolic dysfunction, it may be used to reduce the incidence of CAD outcomes in a subgroup of patients with HR > or =70 bpm. The aim of this short review is to summarize the use of ivabradine in the treatment of CSAP, and its potential utility in atherosclerosis, primitive and dilatative cardiomyopathy, and arrhythmias, such as postural tachycardia syndrome and inappropriate sinus tachycardia, where exclusive lowering of elevated HR may prove beneficial.

Ivabradine: the evidence of its therapeutic impact in angina.

Introduction:Stable angina pectoris (SAP) is a widely prevalent disease affecting 30 000 to 40 000 per million people in Europe and the US. SAP is associated with reductions in quality of life and ability to work, and increased use of healthcare resources. Ivabradine is a drug with a unique therapeutic target, the If current of the sinus node, developed for the treatment of cardiovascular diseases including SAP. It has an exclusive heart rate reducing effect, without any negative effect on left ventricular function or coronary vasodilatation.Aims:The aim of this paper is to review the evidence concerning the use of ivabradine in the treatment of SAP.Evidence review:Ivabradine is an effective antianginal and antiischemic drug, not inferior to the beta blocker atenolol and the calcium channel antagonist (CCA) amlodipine. It decreases the frequency of angina attacks and increases the time to anginal symptoms during exercise. Because of its exclusive chronotropic effect, ivabradine is not associated with the typical adverse reactions associated with beta blockers or other antianginal drugs.Clinical value:Clinical evidence shows that ivabradine is a very good antiischemic and antianginal agent, being as effective as beta blockade and CCA therapy in controlling myocardial ischemia and symptoms of stable angina. Ongoing studies will determine the potential of ivabradine to improve morbidity and mortality in coronary artery disease and heart failure.

Ivabradine: Pharmacodynamic aspects of its clinical use

Ivabradine has been approved as a heart rate-lowering agent for use in the treatment of chronic stable angina pectoris in case of contraindication or intolerance to beta-blockers. This drug effectively lowers the heart rate by inhibiting the pacemaker current I(f) in the sinoatrial node. It appears to induce fewer adverse reactions than other drugs used for reducing the heart rate, such as calcium channel blockers or beta-blockers. Because of this favorable profile, ivabradine could become the first-choice drug when pure heart rate-lowering is the therapeutic goal. This review evaluates experimental and preclinical data to investigate the possibilities, as well as the limitations, of the clinical use of ivabradine. In experimental studies, it has been shown that ivabradine does have some unfavorable pharmacodynamic properties, such as the block of all four hyperpolarization-activated cyclic nucleotide-gated channels and block of other ion channels at high concentrations. Clinical studies, however, indicate that those properties do not result in clinical consequences as long as ivabradine is given at the recommended dose and contraindications are strictly observed.

Clinical Results of If Current Inhibition by Ivabradine

Heart rate reduction is a well accepted and effective approach for the prevention of angina pectoris. Ivabradine is the first selective and specific inhibitor of the I(f) current and provides pure heart rate reduction without altering myocardial contractility. Clinical evidence of the antianginal and anti-ischaemic efficacy and tolerability of ivabradine comes from the largest clinical development programme that has ever been performed in stable angina pectoris, involving more than 5000 patients. Ivabradine at the dosages of 5 or 7.5mg twice daily is as effective as reference antianginal approaches such as beta-adrenoceptor antagonists and calcium channel antagonists. The clinical efficacy and safety of ivabradine has also been confirmed in a 1-year follow-up study. Ivabradine is well tolerated and free from the most commonly observed adverse effects of currently prescribed antianginal drugs. Visual symptoms can occur in a minority of patients treated with ivabradine and are not associated with structural ocular changes. The ongoing clinical development programme with the two major morbidity-mortality studies, BEAUTIFUL and SHIfT, has the potential to greatly extend the use of ivabradine in patients with coronary artery disease as well as in those with heart failure.