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Therapeutic Advances in Cardiovascular... 2020Ivabradine is a pure heart-rate lowering drug that is nowadays used, accordingly to the last ESC Guidelines, to reduce mortality and heart failure (HF) hospitalization... (Review)
Review
Ivabradine is a pure heart-rate lowering drug that is nowadays used, accordingly to the last ESC Guidelines, to reduce mortality and heart failure (HF) hospitalization in patients with HF with reduced ejection fraction and in symptomatic patiens with inappropriate sinus tachycardia. Moreover, interesting effect of ivabradine on endothelial and myocardial function and on oxidative stress and inflamation pathways are progressively emerging. The aim of this paper is to highlight newer evidences about ivabradine effect (and consequently possible future application of the drug) in pathological settings different from guidelines-based clinical practice.
Topics: Animals; Atrial Function; Cardiovascular Agents; Cardiovascular Diseases; Endothelium, Vascular; Hemodynamics; Humans; Inflammation Mediators; Ivabradine; Myocytes, Cardiac; Oxidative Stress; Ventricular Function
PubMed: 32611276
DOI: 10.1177/1753944720934937 -
Expert Opinion on Drug Safety May 2019Heart failure with reduced ejection fraction (HFrEF) is associated with a worse outcome. Heart rate (HR) is related to outcome in HFrEF. Ivabradine selectively inhibits... (Review)
Review
INTRODUCTION
Heart failure with reduced ejection fraction (HFrEF) is associated with a worse outcome. Heart rate (HR) is related to outcome in HFrEF. Ivabradine selectively inhibits I (funny) channels in a concentration-dependent manner reducing HR.
AREAS COVERED
The effects of ivabradine in HF were reviewed. The SHIFT trial results indicated that ivabradine improves chronic HFrEF outcomes, whereas published data suggest that amiodarone, digoxin, or verapamil may not be safe or the safety is controversial in HFrEF patients. In the CONSTATHE-DHF study, ivabradine reduced HR and improved left ventricular (LV) ejection fraction, LV diastolic functions, and right ventricle function in acute decompensated HF (ADHF). In chagasic patients, ivabradine reduced HR and a trend toward reduction in all-cause death was observed with ivabradine ( = 0.07). In children with HFrEF, ivabradine increased NYHA functional class. The most common side effects with ivabradine are bradycardia, atrial fibrillation, and phosphenes. Ivabradine was approved for HFrEF treatment by the EMA and FDA and seems to be cost-effective in HFrEF treatment. Ivabradine is indicated for HFrEF by the ESC HF Guidelines (IIa) and by the 2016 ACC/AHA/HFSA Guidelines (IIa-B-R).
EXPERT OPINION
Published evidences demonstrate that ivabradine improves the outcome of chronic HFrEF and it seems to have a promising role in ADHF.
Topics: Animals; Cardiovascular Agents; Dose-Response Relationship, Drug; Heart Failure; Heart Rate; Humans; Ivabradine; Practice Guidelines as Topic; Stroke Volume; Ventricular Function, Left
PubMed: 31074301
DOI: 10.1080/14740338.2019.1612873 -
Circulation Journal : Official Journal... Jan 2019Higher heart rate (HR) is independently related to worse outcomes in various cardiac diseases, including hypertension, coronary artery disease, and heart failure (HF).... (Review)
Review
Higher heart rate (HR) is independently related to worse outcomes in various cardiac diseases, including hypertension, coronary artery disease, and heart failure (HF). HR is determined by the pacemaker activity of cells within the sinoatrial node. The hyperpolarization-activated cyclic nucleotide-gated (HCN) 4 channel, one of 4 HCN isoforms, generates the I current and plays an important role in the regulation of pacemaker activity in the sinoatrial node. Ivabradine is a novel and only available HCN inhibitor, which can reduce HR and has been approved for stable angina and chronic HF in many countries other than Japan. In this review, we summarize the current knowledge of the HCN4 channel and ivabradine, including the function of HCN4 in cardiac pacemaking, the mechanism of action of I inhibition by ivabradine, and the pharmacological and clinical effects of ivabradine in cardiac diseases as HF, coronary artery disease, and atrial fibrillation.
Topics: Cardiovascular Diseases; Heart Rate; Humans; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; Ivabradine; Sinoatrial Node
PubMed: 30606942
DOI: 10.1253/circj.CJ-18-1184 -
Journal of the American College of... Sep 2017Heart rate reduction as a therapeutic target has been investigated in adults with heart failure (HF). Ivabradine has shown promising efficacy, but has not been evaluated... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Heart rate reduction as a therapeutic target has been investigated in adults with heart failure (HF). Ivabradine has shown promising efficacy, but has not been evaluated in children. Currently, treatment recommendations for chronic pediatric HF are based mainly on chronic HF guidelines for adults.
OBJECTIVES
The authors explored the dose-response relationship of ivabradine in children with dilated cardiomyopathy and symptomatic chronic HF. The primary endpoint was ≥20% reduction in heart rate from baseline without inducing bradycardia or symptoms.
METHODS
This was a randomized, double-blind, placebo-controlled, phase II/III study with 12 months of follow-up. Children (n = 116) receiving stable HF therapy were randomized to either ivabradine or placebo. After an initial titration period, the dose was adjusted to attain the primary endpoint. Left ventricular function (echocardiography), clinical status (New York Heart Association functional class or Ross class), N-terminal pro-B-type natriuretic peptide, and quality of life (QOL) were assessed.
RESULTS
The primary endpoint was reached by 51 of 73 children taking ivabradine (70%) versus 5 of 41 taking placebo (12%) at varying doses (odds ratio: 17.24; p < 0.0001). Between baseline and 12 months, there was a greater increase in left ventricular ejection fraction in patients taking ivabradine than placebo (13.5% vs. 6.9%; p = 0.024). New York Heart Association functional class or Ross class improved more with ivabradine at 12 months than placebo (38% vs. 25%; p = 0.24). There was a trend toward improvement in QOL for ivabradine versus placebo (p = 0.053). N-terminal pro-B-type natriuretic peptide levels decreased similarly in both groups. Adverse events were reported at similar frequencies for ivabradine and placebo.
CONCLUSIONS
Ivabradine safely reduced the resting heart rate of children with chronic HF and dilated cardiomyopathy. Ivabradine's effect on heart rate was variable, highlighting the importance of dose titration. Ivabradine treatment improved left ventricular ejection fraction, and clinical status and QOL showed favorable trends. (Determination of the efficacious and safe dose of ivabradine in paediatric patients with dilated cardiomyopathy and symptomatic chronic heart failure from ages 6 months to 18 years; ISRCTN60567801).
Topics: Adolescent; Benzazepines; Cardiomyopathy, Dilated; Cardiovascular Agents; Child; Child, Preschool; Dose-Response Relationship, Drug; Double-Blind Method; Echocardiography; Female; Follow-Up Studies; Heart Failure; Humans; Infant; Ivabradine; Male; Quality of Life; Stroke Volume; Time Factors; Treatment Outcome; Ventricular Function, Left
PubMed: 28859790
DOI: 10.1016/j.jacc.2017.07.725 -
Cardiovascular Drugs and Therapy Oct 2021Ivabradine is a unique agent that is distinct from beta-blockers and calcium channel blockers as it reduces heart rate without affecting myocardial contractility or... (Review)
Review
Ivabradine is a unique agent that is distinct from beta-blockers and calcium channel blockers as it reduces heart rate without affecting myocardial contractility or vascular tone. Ivabradine is a use-dependent inhibitor targeting the sinoatrial node. It is approved for use in the United States as an adjunct therapy for heart rate reduction in patients with heart failure with reduced ejection fraction. In this scenario, ivabradine has demonstrated improved clinical outcomes due to reduction in heart failure readmissions. However, there has been conflicting evidence from prospective studies and randomized controlled trials for its use in stable ischemic heart disease regarding efficacy in symptom reduction and mortality benefit. Ivabradine may also play a role in the treatment of patients with inappropriate sinus tachycardia, who often cannot tolerate beta-blockers and/or calcium channel blockers. In this review, we highlight the evidence for the nuances of using ivabradine in heart failure, stable ischemic heart disease, and inappropriate sinus tachycardia to raise awareness for its vital role in the treatment of select populations.
Topics: Cardiovascular Agents; Cardiovascular Diseases; Humans; Ivabradine; Myocardial Ischemia; Prospective Studies; Randomized Controlled Trials as Topic; Stroke Volume; Tachycardia, Sinus
PubMed: 33411112
DOI: 10.1007/s10557-020-07124-4 -
Journal of the American College of... Feb 2021Postural orthostatic tachycardia syndrome (POTS) is a complex, multifaceted disorder that impairs functional status and quality of life. Current pharmacological... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Postural orthostatic tachycardia syndrome (POTS) is a complex, multifaceted disorder that impairs functional status and quality of life. Current pharmacological treatments are limited.
OBJECTIVES
This study investigated the effect of ivabradine (selective blocker of the I channel in the sinoatrial node) on heart rate, quality of life (QOL), and plasma norepinephrine (NE) levels in patients with hyperadrenergic POTS defined by plasma NE >600 pg/ml and abnormal tilt table test.
METHODS
In total, 22 patients with hyperadrenergic POTS as the predominant subtype completed a randomized, double-blinded, placebo-controlled, crossover trial with ivabradine. Patients were randomized to start either ivabradine or placebo for 1 month, and then were crossed over to the other treatment for 1 month. Heart rate, QOL, and plasma NE levels were measured at baseline and at the end of each treatment month.
RESULTS
The average age was 33.9 ± 11.7 years, 95.5% were women (n = 21), and 86.4% were White (n = 23). There was a significant reduction in heart rate between placebo and ivabradine (p < 0.001). Patients reported significant improvements in QOL with RAND 36-Item Health Survey 1.0 for physical functioning (p = 0.008) and social functioning (p = 0.021). There was a strong trend in reduction of NE levels upon standing with ivabradine (p = 0.056). Patients did not experience any significant side-effects, such as bradycardia or hypotension, with ivabradine.
CONCLUSION
Ivabradine is safe and effective in significantly improving heart rate and QOL in patients with hyperadrenergic POTS as the predominant subtype.
Topics: Adult; Cardiovascular Agents; Cross-Over Studies; Double-Blind Method; Female; Heart Rate; Humans; Ivabradine; Male; Norepinephrine; Postural Orthostatic Tachycardia Syndrome; Quality of Life
PubMed: 33602468
DOI: 10.1016/j.jacc.2020.12.029 -
International Journal of Cardiology Jun 2017Ivabradine is a heart rate reducing agent that exhibits anti-ischemic effects through the inhibition of funny electrical current in the sinus node resulting in heart... (Review)
Review
Ivabradine is a heart rate reducing agent that exhibits anti-ischemic effects through the inhibition of funny electrical current in the sinus node resulting in heart rate reduction, thus enabling longer diastolic perfusion time, and reduced myocardial oxygen consumption without detrimental changes in arterial blood pressure, coronary vasomotion, and ventricular contractility. The current guideline-based clinical use of Ivabradine is reserved for patients with stable angina pectoris who cannot tolerate or whose symptoms are inadequately controlled with beta blockers. In patients with chronic heart failure and reduced ejection fraction, Ivabradine has demonstrated beneficial effects in improving clinical outcomes when added to conventional therapy. However, the role of Ivabradine in acute coronary syndromes has not been established. Based on the results from some relevant preclinical studies and a limited amount of clinical data that were reported recently, the role of Ivabradine in acute ischemic events warrants further investigation. The aim of this review is to provide an overview of the available literature on the potential role of Ivabradine in the clinical context of acute coronary syndromes.
Topics: Acute Coronary Syndrome; Benzazepines; Cardiovascular Agents; Cyclic Nucleotide-Gated Cation Channels; Heart Rate; Humans; Ivabradine; Treatment Outcome
PubMed: 28256323
DOI: 10.1016/j.ijcard.2017.02.046 -
International Heart Journal Jul 2021Heart rate modulation therapy using ivabradine improves mortality and morbidity in patients with systolic dysfunction. However, a target heart rate remains uncertain.... (Review)
Review
Heart rate modulation therapy using ivabradine improves mortality and morbidity in patients with systolic dysfunction. However, a target heart rate remains uncertain. Echocardiography-guided ivabradine therapy, in which we attempt to approach zero overlap between two diastolic filling inflow waves, has recently been proposed to maximize cardiac output, facilitate reverse remodeling, and reduce mortality and morbidity, instead of using an absolute value for the target heart rate. Prospective studies are needed to validate the clinical implication of these therapeutic strategies. Also, this concept should be expanded to other clinical scenarios.
Topics: Cardiac Output; Cardiovascular Agents; Echocardiography, Doppler; Heart Failure; Heart Rate; Humans; Ivabradine
PubMed: 34276025
DOI: 10.1536/ihj.21-355 -
JACC. Clinical Electrophysiology Aug 2021
Topics: Anti-Arrhythmia Agents; Humans; Ivabradine; Tachycardia, Ectopic Junctional
PubMed: 34412869
DOI: 10.1016/j.jacep.2021.03.015 -
Indian Heart Journal Dec 2018Increased heart rate (HR) is associated with deleterious effects on several disease conditions. Chronic heart failure (CHF) is one of the cardiovascular diseases with... (Review)
Review
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.
Topics: Cardiovascular Agents; Cardiovascular Diseases; Cause of Death; Global Health; Humans; Ivabradine; Survival Rate
PubMed: 30595304
DOI: 10.1016/j.ihj.2018.08.008