Efficacy Of Ivabradine Research Articles

Attenuation of hemodynamic response to laryngoscopy and endotracheal intubation using oral ivabradine – Randomised controlled trial

Endotracheal intubation is one of the most common procedures, and anesthesiologists play an important role in patient care. During laryngoscopy and intubation, the patient can experience rapid and drastic hemodynamic changes that are potentially fatal. The purpose of this study is to know the efficacy of ivabradine in attenuating the hemodynamic response to laryngoscopy and endotracheal intubation. In this prospective randomised double-blinded study, fifty patients belonging to ASA 1 and 2 were randomised to group A - ivabradine 5mg (first dose on the evening before the day of surgery and the second dose one hour before intubation). Patients in group B received tablet MVT (placebo) (first dose on the evening before the day of surgery and the second dose one hour before intubation). Patients in group A showed attenuation of heart rate during laryngoscopy and intubation till 10minutes after intubation. Patients in group B showed a rise in blood pressure during laryngoscopy and intubation till 10 minutes after intubation. Patients in group A and group B showed no significant difference in hemodynamics when monitored intraoperatively. All patients recovered fully from anaesthesia and had no complications such as severe bradycardia. Ivabradine effectively attenuates the hemodynamic stress response without a fall in blood pressure and without severe bradycardia.

Safety and Efficacy of Ivabradine as a Rate Control for the Heart in Sepsis

Abstract Background Sepsis and septic shock represent a major health problem among the critically ill patients all over the world, with associated substantial morbidity and mortality rates ranging from 18 % to 50 %. The incidence of sepsis has increased steadily over the last three decades, at least in part because of aging western population. Despite our increased understanding, improved support and more powerful antibiotic therapy, sepsis is still reported as the second leading cause of death in non-coronary intensive care units, and the tenth-mostcommon cause of death overall (the first being heart disease). Children under 12 months and elderly have the highest incidence of severe sepsis). Objective Evaluation of the role of heart rate control using enteral Ivabradine in the management of patients with sepsis. Assessment of the effect of enteral Ivabradine on outcome of septic patients regarding need for vasopressor therapy, mechanical ventilation, renal replacement therapy, length of ICU stay, in- hospital mortality and 30 days mortality. Patients and Methods The study was comparative prospective case / control study conducted on 60 critically ill patients admitted with sepsis and or septic shock to the Critical Care Department at Kobry Elkoba Military complex at 12 month from 8/2019 up to 8/ 2020. Results Significant decrease in follow up lactate at end of Ivabradine treatment, compared to control group without Ivabradine treatment (p = 0.025). Significant decrease in follow up of crp level in group A than group B at day 2 and day 4 with (p = 0.013), (p = 0.018) respectively. Significant decrease in heart rate in group A in comparison with group B during first 48 hour with (p = 0.008). Significant difference between group A and group B regarding weaning from mechanical ventilation with (p = 0.001). There was no statistically significant difference found between group A and group B regarding rate of mortality with p-value = 0.606. Conclusion Use of enteral Ivabradine can reduce pathologically elevated heart rate in patients with sepsis but didn‘t affect survival, length of ICU stay, between septic patient.

Efficacy of ivabradine in heart failure patients with a high-risk profile (analysis from the SHIFT trial).

Early start and patient profile-oriented heart failure (HF) management has been recommended. In this post hoc analysis from the SHIFT trial, we analysed the treatment effects of ivabradine in HF patients with systolic blood pressure (SBP)<110mmHg, resting heart rate (RHR)≥75b.p.m., left ventricular ejection fraction (LVEF)≤25%, New York Heart Association (NYHA) Class III/IV, and their combination. The SHIFT trial enrolled 6505 patients (LVEF≤35% and RHR≥70b.p.m.), randomized to ivabradine or placebo on the background of guideline-defined standard care. Compared with placebo, ivabradine was associated with a similar relative risk reduction of the primary endpoint (cardiovascular death or HF hospitalization) in patients with SBP<110 and ≥110mmHg [hazard ratio (HR) 0.89, 95% confidence interval (CI) 0.74-1.08 vs. HR 0.80, 95% CI 0.72-0.89, P interaction=0.34], LVEF≤25% and >25% (HR 0.85, 95% CI 0.72-1.01 vs. HR 0.80, 95% CI 0.71-0.90, P interaction=0.53), and NYHA III-IV and II (HR 0.83, 95% CI 0.74-0.94 vs. HR 0.81, 95% CI 0.69-0.94, P interaction=0.79). The effect was more pronounced in patients with RHR≥75 compared with <75 (HR 0.76, 95% CI 0.68-0.85 vs. HR 0.97, 95% CI 0.81-0.1.16, P interaction=0.02). When combining these profiling parameters, treatment with ivabradine was also associated with risk reductions comparable with patients with low-risk profiles for the primary endpoint (relative risk reduction 29%), cardiovascular death (11%), HF death (49%), and HF hospitalization (38%; all P values for interaction: 0.40). No safety concerns were observed between study groups. Our analysis shows that RHR reduction with ivabradine is effective and improves clinical outcomes in HF patients across various risk indicators such as low SBP, high RHR, low LVEF, and high NYHA class to a similar extent and without safety concern.

An Observational Study on Long Term Safety and Efficacy of Ivabradine in Patients with Chronic Heart Failure

The chief objective of the study is to find out the safety and efficacy of ivabradine in patients with chronic heart failure. A prospective observational study has been guided in the cardiology department of tertiary care hospital. The data is collected from the out-patient and in- patient department after considering inclusion and exclusion principles for 6 months and a total of 220 patients were analyzed with data collection form by interviewing to the patients about the Socio-demographic questionnaire, MLHFQ (Minnesota Living and Heart Failure Questionnaire) for the evaluation of safety and efficacy of ivabradine and quality of life after Heart Failure. Statistical tools like the Chi-square test were applied to the data by using SPSS software. A total amount of 220 Heart Failure patients, males 148 (67.3%) patients were predominant over female patients of 72 (32.7%). The majority of the Heart Failure patients were under the peer group of &gt;60 years (100%), symptoms were more in males (46%), past medical history i.e. Hypertension and Diabetes mellitus were more in number (128), Coronary Artery Disease (Anterior Wall Myocardial Infraction) (32), Non ST Elevated Myocardial Infraction (8). Most of the patients were treated with the dose of ivabradine i.e. 5mg rather than 2.5mg or 7.5mg. Among 5mg (90.9%), 2.5mg (5.5%) and 7.5mg (3.6%). The ivabradine is used for decreasing Heart Rate among all age groups i.e. &gt;35 years are having more Heart Rate before ivabradine intake. After ivabradine intake, the normal Heart Rate is seen in age groups of 35- 40 years. Adverse effects of ivabradine are bradycardia (10%), Hypertension (8.9%), atrial fibrillation (8.3%), and luminous phenomenon (2.8%). Heart Failure is mostly seen in males and elderly people. The present study shows the safety and efficacy with respect to ivabradine in patient with congestive Heart Failure. After intake of ivabradine, the Heart Rate was bought to normal which shows the efficacy of the drug and the adverse effects are bradycardia, hypertension, atrial fibrillation, luminous phenomenon. But these adverse reactions were not seen in the sample size. This shows the safety of the drug.

Ivabradine Induced Safety and Efficacy in Patients with Chronic Heart Failure: A Retrospective Study

Abstract: Background: Heart failure is a disabling condition affecting 26 million people worldwide. Progress in understanding of the pathogenesis of HF has led to new treatments, which include If channel inhibitor ivabradine, which acts selectively and specifically by inhibiting the cardiac pacemaker current If. The purpose of the study is to evaluate the safety and efficacy of ivabradine in HF patients. Materials and Methods: It was a retrospective, observational single-center study done in the Kottayam district of Kerala with a sample size of 391 patients with Chronic Heart Failure, and the data was collected from 2016-2020 using a structured data collection form. Various statistical tests were conducted using SPSS-version 16. Results: Among 391 patients with chronic heart failure 65.22% were males and the remaining were females. A significant reduction in heart rate was observed in patients taking Ivabradine compared to patients not taking Ivabradine. It also reduced the number of hospitalizations among patients. ADR was reported in 27 patients. A greater proportion of patients (188 patients) has been administered with Ivabradine 5mg BD. 128 patients were given 2.5mg BD,49 patients were prescribed with 5mg TID and only 26 patients were given 5 mg OD tablets. Conclusion: Ivabradine is the only agent shown to clinically lower the heart rate without negative inotropism on conduction and contractility. Increased heart rate produces an adverse impact on the myocardium. Ivabradine is an attractive, effective, and safe choice in patients with heart failure. Key words: Heart failure, Heart rate, Ivabradine, Standard therapy, Treatment outcome, Efficacy

PO-638-01 THE FUTURE OF ACLS: IVABRADINE’S ROLE FOR THE TREATMENT OF REFRACTORY VENTRICULAR ARRHYTHMIAS

Ivabradine (IVA) is an attractive antiarrhythmic for the treatment of refractory ventricular arrhythmias (RVA) as it does not affect blood pressure or prolong the QT interval. IVA's efficacy in ventricular tachycardia (VT)/ventricular fibrillation (VF) has been validated in multiple animal studies. We present a case series demonstrating complete resolution of RVA in humans with the addition of IVA. Illustrate the outcomes of RVA with the treatment of IVA. Retrospective case series analysis of 4 patients treated with IVA for RVA. Pt 1: 63M with ischemic cardiomyopathy was admitted for RVA despite amiodarone, quinidine, and a beta blocker. IVA 2.5mg BID was initiated with resolution of VF. Pt 2: 61F was admitted with cardiogenic shock secondary to giant cell myocarditis complicated with VT/VF. IVA 2.5mg BID was initiated for RVA despite amiodarone and quinidine. IVA was up titrated to 5mg BID with resolution of VT/VF. Pt 3: 58M without significant history was admitted with a VF arrest. The addition of IVA 2.5mg BID to amiodarone, quinidine, and procainamide resolved VF burden. Pt 4: 37M with cardiomyopathy with continued VT / VF despite amiodarone, and lidocaine, and Impella mechanical circulatory support. IVA 2.5mg BID was initiated, and lidocaine was weaned. These therapies stabilized his rhythm, allowing for successful left ventricular assist device implant. All four patients’ RVA (Images A, C, E, G) were converted to sinus rhythm (Images B, D, F, H) with the addition of IVA to standard antiarrhythmic drugs (Table 1/Figure 1). IVA may be a beneficial additive treatment for RVA. However, randomized studies are required to determine the clinical success of RVA attenuation with IVA.

Abstract 12849: Invasive Assessment of Hemodynamic Effect of Ivabradine in Post ST Segment Elevation Myocardial Infarction Associated Sinus Tachycardia

Introduction: Post MI tachycardia is associated with increase in cardiac morbidity and mortality. We aimed to assess efficacy and safety of ivabradine to control heart rate in post MI tachycardia patients in whom beta-blockers were intolerant. Hypothesis: We hypothesized that ivabradine in post MI tachycardia patients effectively control heart rate without deteriorating effects on hemodynamics. Methods: STEMI patients with sinus tachycardia (heart rate &gt;120/min) who had intolerance to beta blocker were enrolled. Important exclusions were cardiogenic shock, second /third-degree atrioventricular block, Killip class III/ IV. Patient’s invasive hemodynamic parameters such as MAP (Mean Arterial Pressure), iSV (indexed Stroke Volume), CVP (Central Venous Pressure), cardiac output and cardiac index were measured with help of Edwards LifeSciences Flotrac monitor. Patients received ivabradine till heart rate control (&lt;100/min.) was achieved. The primary objectives were to study ivabradine efficacy to achieve target heart rate, and its effects on hemodynamic parameters and secondary objectives were to assess any adverse events. Results: Mean age was 52.7 ± 9.8 years and 29 (81%) were male. At enrolment, mean heart rate, MAP, iSV and CVP was 128.92±3.3bpm, 87.31±10.46mmHg, 28.19±7.85ml/m 2 , 6.35±2.61 mmHg respectively. At target heart rate ≤1oo/min (mean 96.57±5.29bpm), MAP, iSV and CVP were 82.71±13.70 mmHg (P=0.559), 1.11±6.33ml/m 2 (P=0.087) and 7.7±2.54 mmHg (P=0.122) showed no significant changes. However, cardiac output and cardiac index dropped to 5.22± 1.00 L/min (P=0.005) and 2.96±0.60 L/min/m 2 (P=0.005) but within physiological limits. None of the patient reported hypotension, arrhythmia, heart failure or in-hospital mortality. Conclusions: Invasive hemodynamic evaluation showed oral ivabradine is effective and safe alternative to control heart rate in uncomplicated post MI sinus tachycardia patients who had intolerance to beta-blockers.

Interest of ivabradine in pediatric arrhythmia. About a case and review of the literature

By inhibiting the pacemaker current if of the sinoatrial node (SN), ivabradine was first use as an alternative to betablockers in the treatment of heart failure [1] . For a few years, it has been proposed as an adjuvant therapy for postoperative [2] or congenital junctional ectopic tachycardia [3] . But ivabradine can also be effective on atrial and ventricular abnormal automaticity [4] . We report the case of a 9 years old girl who was diagnosed of polymorphic atrial tachycardia at birth. The child was first treated by amiodarone. When amiodarone had to be withdraw because of thyroid dysfunction, multiple antiarrhythmic drugs were tested alone or in association: betablockers, flecainide, digoxine. Despite medication, the child experimented multiple high rate non-sustained tachycardia per day. After an antiarrhythmic washout, ivabradine was started. Fig. 1 is the patient Holter without any treatment showing a very anarchic rhythm, mostly rapid arrhythmia. Fig. 2 is the patient Holter after only 2 takes of ivabradine that shows a marked efficacy of the drug. Ivabradine inhibits selectively the If current that is responsible of the pacemaker activity of the SN and the AV node. If current can also be responsible of abnormal automaticity of the atrial and ventricular myocardium. In such case, ivabradine is highly effective to control the arrhythmia. Still, ivabradine efficacy is difficult to predict, but regarding its overall safety, it can be tested. In a randomized, double-blind trial of pediatric patient with dilated cardiomyopathy, Bonnet et al. did not report more adverse event with ivabradine than with placebo [5] . The outcome of atrial ectopic arrhythmia in the pediatric population is good: 78% will resolve spontaneously when diagnosed under 3 years old [6] . Ivabradine could be an alternative to catheter ablation in the very young or in pediatric patient with multifocal arrhythmia or organized arrhythmia close to the AV conduction system.

Efficacy of ivabradine in HIV-associated dilated cardiomyopathy.

Ivabradine is a pure heart rate-lowering drug that acts directly on the sinus node and does not affect atrioventricular or intraventricular conduction times, myocardial contractility or ventricular repolarization. Ivabradine is used in the treatment of adults with New York Heart Association (NYHA) class II-IV chronic heart failure (CHF) with systolic dysfunction, in sinus rhythm, with a heart rate of ≥75 beats per minute (bpm). This report describes the beneficial effect of ivabradine on clinical parameters in a HIV-infected patient with dilated cardiomyopathy presenting with NYHA class III CHF symptoms. Ivabradine improved functional capacity and left ventricular (LV) systolic function in our patient with HIV-related dilated cardiomyopathy and CHF. This report also lists the summaries of potential clinically significant interaction, likely to require additional monitoring, alteration of drug dosage or timing of administration, between ivabradine and antiretroviral drugs.

Ivabradine and Blood Pressure Reduction: Underlying Pleiotropic Mechanisms and Clinical Implications

Elevated heart rate (HR) is a well-recognized but somewhat neglected risk factor among the healthy population and various cardiovascular pathologies (1). High HR is fraught with a spate of detrimental cardiovascular consequences including immense myocardial oxygen demand in reduced diastolic perfusion time (2) and low, oscillatory vascular shear stress with high tensile stress triggering endothelial dysfunction (3). Although beta-blockers (BBs) are considered to be the cornerstone treatment of elevated HR in various cardiovascular pathologies, they are associated with negative inotropy, a number of side effects, and undesirable metabolic actions limiting their usage (4, 5). Thus, new approaches to HR reduction are being continuously sought out. The inhibition of the If current in the sinoatrial node (SAN) seems to offer a promising approach to the reduction of elevated HR. Indeed, the SAN's pacemaker cells are inherently capable of cyclic variations of the resting membrane potential necessary for spontaneous depolarization. The SAN's spontaneous slow diastolic depolarization is administered by a mixed sodium/potassium inward current, known as an If current, through the “funny” (f)-channel (6). Structurally, the f-channel belongs to hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels and is activated by both hyperpolarization in the diastolic voltage range and intracellular cyclic adenosine monophosphate (7). Ivabradine selectively inhibits the If current, thus reducing the steepness of SAN's diastolic depolarization, ensuing diastole prolongation without affecting action potential duration or inducing negative inotropy (7, 8). Several studies have assessed ivabradine's efficacy in clinical settings. In the SHIFT study, the investigation of 6,558 patients with systolic heart failure (HF) during a median 22.9 month follow-up period revealed that the addition of ivabradine to an established HF therapy significantly reduced the primary composite endpoint of hospital admission for worsening HF or cardiovascular death. Considering the results of the SHIFT study, ivabradine is recommended for patients with systolic HF and HR above 70 bpm despite an evidence-based optimal medical therapy (with or without BB) to reduce the composite endpoint of hospitalization and mortality (9, 10). The BEAUTIFUL study comprised 10,917 systolic HF patients with HR above 70 bpm suffering from stable coronary artery disease (CAD), and the primary endpoint was a composite of cardiovascular death and hospital admission for acute myocardial infarction or HF. Although neither the primary endpoint nor the cardiovascular death rate improved, ivabradine reduced the secondary endpoints of hospital admissions for myocardial infarction and coronary revascularization (11). However, in the SIGNIFY study involving 19,102 patients with stable CAD but without HF, ivabradine did not reduce the compound primary endpoint of cardiovascular death and myocardial infarction (12). Hypertension, however, is a substantially different condition, and data regarding ivabradine's effect on peripheral blood pressure (BP) in a hypertensive population are scanty. Yet ivabradine's interference with central BP (CBP) was indicated in several studies. Lopatin and Vitale (13) reviewed five studies analyzing ivabradine's effect on CBP in patients with CAD: two studies reported a neutral effect, while in two other studies and in one study, ivabradine decreased and increased CBP, respectively. In 12 normotensive patients with stable CAD and HR ≥ 70 bmp, a 3 week ivabradine treatment reduced brachial systolic and diastolic BP, while the HR reduction did not increase central aortic BP (14). Moreover, in patients with arterial hypertension and CAD treated with ivabradine, the increase in HR between resting conditions and early recovery post exercise showed a trend toward correlation with the radial augmentation index (15). Besides ivabradine's HR-reducing action, which is considered to be a principal mechanism of its benefit, ivabradine exerts a number of pleiotropic effects, some of which may partly be HR independent (16, 17) and some of which are still emerging.

Treatment Updates in Postural Tachycardia Syndrome

Postural tachycardia syndrome is a common condition characterized by the presence of orthostatic intolerance in conjunction with excessive postural tachycardia. This review will focus on treatment updates in postural tachycardia syndrome and will include a discussion of rehabilitative, vasopressor, heart rate modulation, volume expansion, and immunomodulatory treatment strategies. A recent study added to existing literature the benefits of exercise retraining in postural tachycardia syndrome (POTS) patients who were able to successfully complete a 3-month exercise regimen. Another recent, novel study reported the benefits of respiratory retraining in POTS patients reporting breathlessness. The benefits of volume expansion in the treatment of POTS were strengthened by 2 recent studies, including a study demonstrating the value of oral rehydration salts in improving hemodynamic parameters in POTS patients and another prospective study demonstrating the value of IV saline infusions in POTS patients. A recent meta-analysis reviewed the efficacy of ivabradine in the treatment of POTS, while another systematic review and meta-analysis reviewed the benefits of metoprolol in the treatment of childhood and adolescent POTS. Also included in this review is that of a large clinical trial comparing propranolol and bisoprolol alone and with pyridostigmine, demonstrating efficacy of beta blockers and an absence of any clear additive benefit with pyridostigmine. A retrospective review of droxidopa in a large POTS cohort reported improvement in only 27% of POTS patients. Recent approaches to the pharmacologic and non-pharmacologic treatment of cognitive dysfunction and fatigue in POTS patients were reviewed. Finally, a retrospective series of the benefits of intravenous immunoglobulin in POTS suspected of being autoimmune is reviewed. The treatment of postural tachycardia syndrome is complex and nuanced, requiring a combination of lifestyle and pharmacologic treatments in most patients. This review provides treatment updates for this enigmatic condition.

The efficacy of Ivabradine and Nebivolol in the Treatment of Stable Angina Pectoris Patients with Mild Left Ventricular Dysfunction

The efficacy of Ivabradine and Nebivolol in the Treatment of Stable Angina Pectoris Patients with Mild Left Ventricular Dysfunction

Ivabradine alone and in combination with metoprolol reduces the incidence of major adverse cardiac events in patients with heart failure: A prospective study

Background: Altered hemodynamics of heart failure patients is associated with an increased heart rate (HR). The effect of β-blockers on prognosis has been linked to their HR lowering effect. Ivabradine is an If current inhibitor and it decreases the heart rate. Aims and Objectives: The aim of this study was to compare the efficacy of ivabradine, a combination of ivabradine and metoprolol, with that of metoprolol alone in patients with heart failure. Materials and Methods: This prospective observational study was done in patients with New York Heart Association (NYHA) Class III/IV heart failure over 18 months. Patients were categorized into Group A: Ivabradine (5 mg BD), Group B: Metoprolol (12.5 mg BD), and Group C: Combination of both (5 mg BD and 12.5 mg BD). At the end of 6 months follow-up, the outcomes of therapy were assessed based on the occurrence of major adverse cardiac events (MACE) such as acute coronary syndrome, rehospitalization, or death. Effectiveness was also measured in terms of a decrease in HR, improvement in left ventricular ejection fraction (LVEF), and NYHA functional class. Results: One hundred and fifty-two patients were included in this study in three groups – 51 patients in Group A, 50 patients in Group B, and 51 patients in Group C. At the end of follow-up period, it was found that the highest number of MACE occurred in Group B followed by A and C. Group C showed significant improvement with therapy in terms of decrease in HR, increase in LVEF, and improvement in NYHA class. Conclusion: Administration of ivabradine alone or a combination of ivabradine and metoprolol is more effective than metoprolol in reducing the incidence of MACE in heart failure.

Clinical and Electrophysiological Correlates of Incessant Ivabradine-Sensitive Atrial Tachycardia

Incessant focal atrial tachycardia (FAT), if untreated, can lead to ventricular dysfunction and heart failure (tachycardia-induced cardiomyopathy). Drug therapy of FAT is often difficult and ineffective. The efficacy of ivabradine has not been systematically evaluated in the treatment of FAT. The study group consisted of patients with incessant FAT (lasting >24 hours) and structurally normal hearts. Patients with ventricular dysfunction as a consequence of FAT were not excluded. All antiarrhythmic drugs were discontinued at least 5 half-lives before the initiation of ivabradine. Oral ivabradine (adults, 10 mg twice 12 hours apart; pediatric patients: 0.28 mg/kg in 2 divided doses) was initiated in the intensive care unit under continuous electrocardiographic monitoring. A positive response was defined as the termination of tachycardia with the restoration of sinus rhythm or suppression of the tachycardia to <100 beats per minute without termination within 12 hours of initiating ivabradine. Twenty-eight patients (mean age, 34.6±21.5 years; women, 60.7%) were included in the study. The most common symptom was palpitation (85.7%) followed by shortness of breath (25%). The mean atrial rate during tachycardia was 170±21 beats per minute, and the mean left ventricular ejection fraction was 54.7±14.3%. Overall, 18 (64.3%) patients responded within 6 hours of the first dose of ivabradine. Thirteen of 18 ivabradine responders subsequently underwent successful catheter ablation. FAT originating in the atrial appendages was a predictor of ivabradine response compared with those arising from other atrial sites (P=0.046). Ivabradine-sensitive atrial tachycardia constitutes 64% of incessant FAT in patients without structural heart disease. Incessant FAT originating in the atrial appendages is more likely to respond to ivabradine than that arising from other atrial sites. Our findings implicate the funny current in the pathogenesis of FAT.

Ivabradine Improves Cardiac Function and Increases Exercise Capacity in Patients with Chronic Heart Failure.

To systematically review and conduct a meta-analysis of the ivabradine-induced improvement in cardiopulmonary function, exercise capacity, and primary composite endpoints in patients with chronic heart failure (CHF).This study was a systematic review and meta-analysis.Databases, including PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Clinical Trials and European Union Clinical Trials, were searched for randomized placebo-controlled trials. The efficacy and safety of ivabradine treatment in patients with CHF were assessed and compared to those of the standard anti-heart failure treatment. Review Manager 5.3 software was used to analyze the relative risk (RR) for dichotomous data and the mean difference (MD) for continuous data.In total, 22 studies with 24,562 patients were included. Cardiopulmonary function analysis showed that treatment with added ivabradine reduced the heart rate (MD = -17.30, 95% confidence interval (CI): 19.52--15.08, P < 0.00001), significantly increased the left ventricular ejection fraction (LVEF) (MD = 3.90, 95% CI: 0.40-7.40, P < 0.0001), and led to a better New York Heart Association (NYHA) classification. Ivabradine significantly reduced the minute ventilation/carbon dioxide production (VE/VCO2) (MD = -2.68, 95% CI: -4.81--0.55, P = 0.01) and improved the peak VO2 (MD = 2.80, 95% CI: 1.05-4.55, P = 0.002) and the exercise capacity, including the exercise duration with a submaximal load (MD = 7.82, 95% CI: -2.57--18.21, P < 0.00001) and the 6-minute walk distance. The RR of cardiovascular death or worsening heart failure was significantly decreased (RR = 0.93, 95% CI: 0.87--0.98, P = 0.01) in the patients treated with ivabradine. Additionally, the RRs of heart failure and hospitalization also decreased (RR = 0.91, 95% CI: 0.85--0.97, P = 0.006; RR = 0.86, 95% CI: 0.79--0.93, P = 0.0002). Safety analysis showed no significant difference in the RR of severe adverse events between the ivabradine group and the standard anti-heart failure treatment group (P = 0.40). However, ivabradine significantly increased the RR of visual symptoms in CHF patients (RR = 3.82, 95% CI: 1.80--8.13, P = 0.0005).Existing evidence showed that adding ivabradine treatment significantly improved the cardiopulmonary function and increased the exercise capacity of patients with CHF. Adding ivabradine to the standard anti-heart failure treatment reduced the mortality and hospitalization risk and improved the quality of life. Finally, ivabradine significantly increased the RR of visual symptoms in CHF patients.This is the first systematic review and meta-analysis to focus on the efficacy of ivabradine, which improved the cardiac function and increased the exercise capacity in patients with chronic heart failure (CHF). Therefore, this study will help evaluate the quality of life after adding ivabradine to the treatment of patients with CHF, even though there are differences in the standard for resting heart rate, left ventricular ejection fraction (LVEF), and New York Heart Association (NYHA) class in the included studies. This hybrid effect might be smaller when analyzed separately but might have a higher heterogeneity when analyzed in multiple studies.

Efficacy of Ivabradine in Combination with Beta-Blockers Versus Uptitration of Beta-Blockers in Patients with Stable Angina (CONTROL-2 Study).

IntroductionHeart rate (HR) reduction is an integral part of antianginal therapy, but many patients do not reach the guideline-recommended target of less than 60 bpm despite high use of beta-blockers (BB). Failure to uptitrate BB doses may be partly to blame. To explore other options for lowering HR and improving angina control, CONTROL-2 was initiated to compare the efficacy and tolerability of the combination of BBs with ivabradine versus uptitration of BBs to maximal tolerated dose, in patients with stable angina.MethodsThis multicenter, open, randomized study included 1104 patients with Canadian Cardiovascular Society (CCS) class II or III stable angina, in sinus rhythm, and on background stable treatment with non-maximal recommended doses of BBs. Consecutive patients were allocated to ivabradine + BB or BB uptitration in a 4:1 ratio.ResultsAt the end of the study (week 16), addition of ivabradine to BB treatment and BB uptitration resulted in reduction in HR (61 ± 6 vs. 63 ± 8 bpm; p = 0.001). At week 16, significantly more patients on ivabradine + BB were in CCS class I than with BB uptitration (37.1% vs. 28%; p = 0.017) and significantly more patients were angina-free (50.6% vs. 34.2%; p < 0.001). Patient health status based on the visual analogue scale (VAS) was also better in the ivabradine + BB group. Adverse events (AEs) were significantly more common with BB uptitration than with the ivabradine + BB combination (18.4% vs. 9.4%, p < 0.001).ConclusionIn patients with stable angina, combination therapy with ivabradine + BB demonstrated good tolerability, safety, and more pronounced clinical improvement, compared to BB uptitration.Trial RegistrationISRCTN30654443.FundingServier.

Safety profile and efficacy of ivabradine in heart failure due to Chagas heart disease: a post hoc analysis of the SHIFT trial.

AimsThe SHIFT trial showed that ivabradine reduced heart rate (HR) and the risk of cardiovascular outcomes. Concerns remain over the efficacy and safety of ivabradine on heart failure (HF) due to Chagas disease (ChD). We therefore conducted a post hoc analysis of the SHIFT trial to investigate the effect of ivabradine in these patients.Methods and resultsSHIFT was a randomized, double‐blind, placebo‐controlled trial in symptomatic systolic stable HF, HR ≥ 70 b.p.m., and in sinus rhythm. The ChD HF subgroup included 38 patients, 20 on ivabradine, and 18 on placebo. The ChD HF subgroup showed high prevalence of bundle branch right block and, compared with the overall SHIFT population, lower systolic blood pressure; higher use of diuretics, cardiac glycosides, and antialdosterone agents; and lower use of angiotensin‐converting enzyme inhibitor/angiotensin II receptor blocker or target daily dose of beta‐blocker. ChD HF presented a poor prognosis (all‐cause mortality at 2 years was ~60%). The mean twice‐daily dose of ivabradine was 6.26 ± 1.15 mg and placebo 6.43 ± 1.55 mg. Ivabradine reduced HR from 77.9 ± 3.8 to 62.3 ± 10.1 b.p.m. (P = 0.005) and improved functional class (P = 0.02). A trend towards reduction in all‐cause death was observed in ivabradine arm vs. placebo (P = 0.07). Ivabradine was not associated with serious bradycardia, atrioventricular block, hypotension, or syncope.ConclusionsChD HF is an advanced form of HF with poor prognosis. Ivabradine was effective in reducing HR in these patients and improving functional class. Although our results are based on a very limited sample and should be interpreted with caution, they suggest that ivabradine may have a favourable benefit–risk profile in ChD HF patients.

Effect of ivabradine on cardiovascular outcomes in patients with stable angina: meta-analysis of randomized clinical trials

BackgroundAlthough there are established drugs for treatment of cardiovascular diseases, due to adverse effects these drugs may not be clinically applicable to all patients. Recent trends have seen the emergence of drugs which act on funny current channels to induce selective heart rate reduction. Ivabradine is one such drug developed for coronary artery disease and heart failure. There is inconsistent evidence about the effect of this selective inhibitor in reduction of cardiovascular related mortality and morbidity. Such an inconsistency warrants the need for a meta-analysis to consider the effectiveness and efficacy of Ivabradine in the treatment of coronary artery disease and heart failure.MethodsRandomized controlled trials with a minimum follow-up period of one year were searched in Pub Med/Medline, Embase, Cochrane Central Register of Controlled Trials published between 1980 and 2016.Each eligible study was assessed for risk of bias by using the Cochrane Risk of Bias Assessment tool. The outcomes assessed in this study included: all cause mortality, cardiovascular-related mortality, hospitalization for new or worsening heart failure, and adverse events. Subgroup analysis and publication bias were assessed. We used Mantel-Haenszel method for random-effects. Analysis was done using RevMan5.1™.This study was registered in PROSPERO as [PROSPERO 2016:CRD42016035597].ResultThree trials with a total of 36,577 participants met the meta-analysis criteria. Pooled analysis showed that ivabradine is not effective in reducing cardiovascular deaths (OR: 1.02; CI:0.91–1.15,P = 0.74), all-cause mortality (OR:1.00; CI:0.91–1.10,P = 0.98), coronary revascularization (OR: 0.93, CI: 0.77–1.11, P = 0.41) and hospital admission for worsening of heart failure (OR: 0.94, CI: 0.71–1.25, P = 0.69). However, the drug was found to significantly increase adverse events: phosphenes (OR:7.77, CI: 4.4–14.6,P < 0.00001), blurred vision (OR:3.07,CI:2.18–4.32,P < 0.00001), symptomatic bradycardia (OR: 6.23, CI: 4.2–9.26, P < 0.00001), and atrial fibrillation (OR: 1.35, CI: 1.19–1.53, P < 0.0001). Subgroup analysis by duration of follow up on cardiovascular outcomes found that there is no difference in effect of ivabradine depending on the duration of follow up. There was no publication bias in reporting of included studies.ConclusionThis meta-analysis suggests that ivabradine is not effective in reducing cardiovascular-related morbidity and mortality unless used for specific conditions. On the contrary, the use of this drug was strongly associated with the onset of untoward and new adverse events. This finding strongly supports previous findings and further informs the rational and evidence-informed clinical use of ivabradine.

POSSIBILITIES OF IVABRADINE, A SELECTIVE INHIBITOR OF ION F-CHANNELS OF SINUS NODE, IN PREVENTION OF ANTHRACYCLINE CARDIOTOXICITY IN PATIENTS WITH BREAST CANCER

Aim. To study the efficacy of ivabradine in the prevention of cardiotoxic effects due to chemotherapeutic drugs in patients with breast cancer. Material and methods. The open randomized uncontrolled study included 55 patients with breast cancer who had to undergo chemotherapy by anthracyclines. The inclusion criterion was a heart rate >70 beats/min. Collection of complaints and anamnesis, ECG, echocardiography, routine laboratory tests were performed in all patients initially and after 1, 3, 6 and 12 months. All patients were treated with polychemotherapy with anthracyclines in combination with cyclophosphamide and fluorouracil. The patients included into the study were randomized into two groups. Patients of the main group (n=23) were additionally prescribed ivabradine in a daily dose of 10 mg followed by a dose titration. Patients of the control group (n=32) received only polychemotherapy. Results. In the main group a decrease in heart rate was observed already by the first month (from 83.6±9.5 to 67.1±7.5 beats/min, p 0.05). A significant change in the LV ejection fraction was not found in both groups. Significant differences in LV global longitudinal strain were found between groups in 1, 3 and 6 months of observation (p 70 beats/min was safe and did not cause bradycardia. Ivabradine use was accompanied by a significant reduction in a number of patients with complaints of palpitation, contributed to the preservation of normalLV global longitudinal deformation in chemotherapy, while the control group had negative changes with a maximum by the 6th month of follow-up.

Comparison of the safety and efficacy of ivabradine, nebivolol, trimetazidine and ranolazine therapies in the treatment of stable angina pectoris patients with left ventricular dysfunction

Comparison of the safety and efficacy of ivabradine, nebivolol, trimetazidine and ranolazine therapies in the treatment of stable angina pectoris patients with left ventricular dysfunction