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Cardiology 2018Ischaemic heart disease is a major cause of death and disability worldwide, while angina represents its most common symptom. It is estimated that approximately 9 million... (Review)
Review
Ischaemic heart disease is a major cause of death and disability worldwide, while angina represents its most common symptom. It is estimated that approximately 9 million patients in the USA suffer from angina and its treatment is challenging, thus the strategy to improve the management of chronic stable angina is a priority. Angina might be the result of different pathologies, ranging from the "classical" obstruction of a large coronary artery to alteration of the microcirculation or coronary artery spasm. Current clinical guidelines recommend antianginal therapy to control symptoms, before considering coronary artery revascularization. In the current guidelines, drugs are classified as being first-choice (beta-blockers, calcium channel blockers, and short-acting nitrates) or second-choice (ivabradine, nicorandil, ranolazine, trimetazidine) treatment, with the recommendation to reserve second-line modifications for patients who have contraindications to first-choice agents, do not tolerate them, or remain symptomatic. However, such a categorical approach is currently questioned. In addition, current guidelines provide few suggestions to guide the choice of drugs more suitable according to the underlying pathology or the patient comorbidities. Several other questions have recently emerged, such as: is there evidence-based data between first- and second-line treatments in terms of prognosis or symptom relief? Actually, it seems that newer antianginal drugs, which are classified as second choice, have more evidence-based clinical data that are more contemporary to support their use than what is available for the first-choice drugs. It follows that actual guidelines are based more on tradition than on evidence and there is a need for new algorithms that are more individualized to patients, their comorbidities, and pathophysiological mechanism of chronic stable angina.
Topics: Adrenergic beta-Antagonists; Angina, Stable; Calcium Channel Blockers; Cardiovascular Agents; Chest Pain; Humans; Ivabradine; Nicorandil; Patient Selection; Practice Guidelines as Topic; Ranolazine; Treatment Outcome; Trimetazidine
PubMed: 29874661
DOI: 10.1159/000487936 -
Frontiers in Pharmacology 2022In a rapidly growing and aging population, heart failure (HF) has become recognised as a public health concern that imposes high economic and societal costs worldwide.... (Review)
Review
In a rapidly growing and aging population, heart failure (HF) has become recognised as a public health concern that imposes high economic and societal costs worldwide. HF management stems from the use of highly cost-effective angiotensin converting enzyme inhibitors (ACEi) and β-blockers to the use of newer drugs such as sodium-glucose cotransporter-2 inhibitors (SGLT2i), ivabradine, and vericiguat. Modelling studies of pharmacological treatments that report on cost effectiveness in HF is important in order to guide clinical decision making. Multiple cost-effectiveness analysis of dapagliflozin for heart failure with reduced ejection fraction (HFrEF) suggests that it is not only cost-effective and has the potential to improve long-term clinical outcomes, but is also likely to meet conventional cost-effectiveness thresholds in many countries. Similar promising results have also been shown for vericiguat while a cost effectiveness analysis (CEA) of empagliflozin has shown cost effectiveness in HF patients with Type 2 diabetes. Despite the recent FDA approval of dapagliflozin and empagliflozin in HF, it might take time for these SGLT2i to be widely used in real-world practice. A recent economic evaluation of vericiguat found it to be cost effective at a higher cost per QALY threshold than SGLT2i. However, there is a lack of clinical or real-world data regarding whether vericiguat would be prescribed on top of newer treatments or in lieu of them. Sacubitril/valsartan has been commonly compared to enalapril in cost effectiveness analysis and has been found to be similar to that of SGLT2i but was not considered a cost-effective treatment for heart failure with reduced ejection fraction in Thailand and Singapore with the current economic evaluation evidences. In order for more precise analysis on cost effectiveness analysis, it is necessary to take into account the income level of various countries as it is certainly easier to allocate more financial resources for the intervention, with greater effectiveness, in high- and middle-income countries than in low-income countries. This review aims to evaluate evidence and cost effectiveness studies in more recent HF drugs i.e., SGLT2i, ARNi, ivabradine, vericiguat and omecamtiv, and gaps in current literature on pharmacoeconomic studies in HF.
PubMed: 36133814
DOI: 10.3389/fphar.2022.919974 -
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 -
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 -
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 -
European Heart Journal. Cardiovascular... Dec 2022We assessed the efficacy of the drugs developed after neurohormonal inhibition (NEUi) in patients with heart failure (HF) with reduced ejection fraction (HFrEF) and... (Meta-Analysis)
Meta-Analysis
Efficacy of new medical therapies in patients with heart failure, reduced ejection fraction, and chronic kidney disease already receiving neurohormonal inhibitors: a network meta-analysis.
AIMS
We assessed the efficacy of the drugs developed after neurohormonal inhibition (NEUi) in patients with heart failure (HF) with reduced ejection fraction (HFrEF) and concomitant chronic kidney disease (CKD).
METHODS AND RESULTS
The literature was systematically searched for phase 3 randomized controlled trials (RCTs) involving ≥90% patients with left ventricular ejection fraction <45%, of whom <30% were acutely decompensated, and with published information about the subgroup of estimated glomerular filtration rate <60 mL/min/1.73 m2. Six RCTs were included in a study-level network meta-analysis evaluating the effect of NEUi, ivabradine, angiotensin receptor-neprilysin inhibitor (ARNI), sodium-glucose cotransporter-2 inhibitors (SGLT2i), vericiguat, and omecamtiv mecarbil (OM) on a composite outcome of cardiovascular death or hospitalization for HF. In a fixed-effects model, SGLT2i [hazard ratio (HR) 0.78, 95% credible interval (CrI) 0.69-0.89], ARNI (HR 0.79, 95% CrI 0.69-0.90), and ivabradine (HR 0.82, 95% CrI 0.69-0.98) decreased the risk of the composite outcome vs. NEUi, whereas OM did not (HR 0.98, 95% CrI 0.89-1.10). A trend for improved outcome was also found for vericiguat (HR 0.90, 95% CrI 0.80-1.00). In indirect comparisons, both SLGT2i (HR 0.80, 95% CrI 0.68-0.94) and ARNI (HR 0.80, 95% CrI 0.68-0.95) reduced the risk vs. OM; furthermore, there was a trend for a greater benefit of SGLT2i vs. vericiguat (HR 0.88, 95% CrI 0.73-1.00) and ivabradine vs. OM (HR 0.84, 95% CrI 0.68-1.00). Results were comparable in a random-effects model and in sensitivity analyses. Surface under the cumulative ranking area scores were 81.8%, 80.8%, 68.9%, 44.2%, 16.6%, and 7.8% for SGLT2i, ARNI, ivabradine, vericiguat, OM, and NEUi, respectively.
CONCLUSION
Expanding pharmacotherapy beyond NEUi improves outcomes in HFrEF with CKD.
Topics: Humans; Heart Failure, Systolic; Ivabradine; Network Meta-Analysis; Renal Insufficiency, Chronic; Stroke Volume; Ventricular Dysfunction, Left; Clinical Trials, Phase III as Topic; Randomized Controlled Trials as Topic
PubMed: 34928347
DOI: 10.1093/ehjcvp/pvab088 -
Journal of the American College of... Oct 2017The clinical use of ivabradine has and continues to evolve along channels that are predicated on its mechanism of action. It selectively inhibits the funny current (I)... (Review)
Review
The clinical use of ivabradine has and continues to evolve along channels that are predicated on its mechanism of action. It selectively inhibits the funny current (I) in sinoatrial nodal tissue, resulting in a decrease in the rate of diastolic depolarization and, consequently, the heart rate, a mechanism that is distinct from those of other negative chronotropic agents. Thus, it has been evaluated and is used in select patients with systolic heart failure and chronic stable angina without clinically significant adverse effects. Although not approved for other indications, ivabradine has also shown promise in the management of inappropriate sinus tachycardia. Here, the authors review the mechanism of action of ivabradine and salient studies that have led to its current clinical indications and use.
Topics: Benzazepines; Cardiovascular Agents; Cardiovascular Diseases; Cyclic Nucleotide-Gated Cation Channels; Heart Rate; Humans; Ivabradine
PubMed: 28958335
DOI: 10.1016/j.jacc.2017.08.038 -
Hospital Pharmacy Jul 2015Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The...
Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation/medication use evaluation (DUE/MUE) is also provided each month. With a subscription, the monographs are sent in print and are also available on-line. Monographs can be customized to meet the needs of a facility. A drug class review is now published monthly with The Formulary Monograph Service. Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. For more information about The Formulary Monograph Service, call The Formulary at 800-322-4349. The July 2015 monograph topics are ivabradine, dinutuximab, glycopyrronium bromide/indacaterol, patriromer, and idarucizumab. The Safety MUE is on ivabradine.
PubMed: 26445907
DOI: 10.1310/hpj5007-619 -
Deutsches Arzteblatt International Feb 2018Chronic heart failure (CHF) is the most common reason for hospital admissions in Germany. For the National Disease Management Guideline (NDMG) on CHF, a...
BACKGROUND
Chronic heart failure (CHF) is the most common reason for hospital admissions in Germany. For the National Disease Management Guideline (NDMG) on CHF, a multidisciplinary expert panel revised the chapters on drug therapy, invasive therapy, and care coordination, following the methods of evidence-based medicine.
METHODS
Recommendations are based on international guideline adaptations or systematic literature search. They were developed by a multidisciplinary expert panel, approved in a formal consensus procedure, and tested in open consultation, as specified by the requirements for S3 guidelines.
RESULTS
The pharmacological treatment is based on ACE inhibitors, beta-blockers and mineralocorticoid receptor antagonists as well as diuretics to treat fluid retention, if present. Sacubitril/Valsartan and ivabradine showed positive effects on mortality in large but methodologically limited RCT. They are recommended if established combination therapy is not sufficient for symptom control, or if drugs are not tolerated/contraindicated. The indications for pacemakers or defibrillators have been confined to patient subgroups in which clinical trials have shown a clear benefit. Moreover, the goals of treatment and the patient's expectations should be aligned with each other. Structured care programs, specialized nurses, remote, or telephone monitoring showed moderate effects on patient related outcomes in RCT.
CONCLUSION
All patients with heart failure are suggested to be enrolled in a structured program (e.g., a disease management program) including coordinated multidisciplinary care and continuous educational interventions. In patients with a poor prognosis, more intensive care is recommended, e.g. specialized nurses, or telephone support.
Topics: Adrenergic beta-Antagonists; Aminobutyrates; Angiotensin-Converting Enzyme Inhibitors; Biphenyl Compounds; Cardiac Resynchronization Therapy; Diuretics; Drug Combinations; Germany; Guidelines as Topic; Heart Failure; Humans; Ivabradine; Mineralocorticoid Receptor Antagonists; Tetrazoles; Valsartan
PubMed: 29526184
DOI: 10.3238/arztebl.2018.0124