cardiovascular-agents and Heart-Failure--Systolic

This review summarizes the current management of heart failure (HF) in patients with reduced ejection fraction and the potential role of heart rate lowering agents in select populations, as recommended in the updated guidelines. Areas covered: PubMed was searched for studies that evaluated the role of heart rate lowering or ivabradine in HF management. Expert commentary: Targeting heart rate may offer benefit when added to renin-angiotensin aldosterone antagonists, and beta-blockers. Ivabradine is a heart rate lowering agent that acts on the funny current (I

Topics: Adrenergic beta-Antagonists; Benzazepines; Cardiovascular Agents; Chronic Disease; Heart Failure; Heart Failure, Systolic; Heart Rate; Hospitalization; Humans; Ivabradine; Treatment Outcome; Ventricular Dysfunction, Left

We reviewed clinical evidence for the use of ivabradine in systolic heart failure (HF), in which it appears to improve symptoms, improve quality of life, prevent hospitalization, and prolong survival, thereby addressing unmet needs in the management of HF. Ivabradine provides symptomatic benefits in HF on top of standard therapies, in terms of functional parameters and exercise capacity, and there is some evidence that this leads to improvements in quality of life in symptomatic HF patients, who may have dyspnea, altered exercise capacity, and fatigue. The SHIFT trial demonstrated that ivabradine has significant beneficial effects on major outcomes in HF. Ivabradine had a significant effect on pump failure death, which was reduced by 26 % (p = 0.014), with no effect on sudden cardiac death. This is an important result since pump failure death is currently the main cause of death in HF, and also because the reductions in mortality obtained with beta-blockers and spironolactone in the last 20 years appear to be mainly due to reduction in sudden death rather than reduction in pump failure death. Ivabradine also has a beneficial effect on hospital admissions (-26 %, p < 0.0001), which is clinically relevant since a quarter of HF patients can expect to be readmitted to hospital for HF within 1 month of discharge. Ivabradine-treated patients are also at significantly lower risk of experiencing a second or third hospitalization for worsening HF. Ivabradine clearly has a key role to play in the management of HF by covering the main therapeutic objectives of symptoms, quality of life, and outcomes.

Topics: Benzazepines; Cardiovascular Agents; Heart Failure, Systolic; Hospitalization; Humans; Ivabradine; Quality of Life; Treatment Outcome

Heart rate (HR) is a risk factor in patients with chronic systolic heart failure (HF) that, when reduced, provides outcome benefits. It is also a target for angina pectoris prevention and a risk marker in chronic coronary artery disease without HF. HR can be reduced by drugs; however, among those used clinically, only ivabradine reduces HR directly in the sinoatrial nodal cells without other known effects on the cardiovascular system. This review provides current information regarding the safety and efficacy of HR reduction with ivabradine in clinical studies involving >36,000 patients with chronic stable coronary artery disease and >6,500 patients with systolic HF. The largest trials, Morbidity-Mortality Evaluation of the I

Topics: Benzazepines; Cardiovascular Agents; Chronic Disease; Coronary Artery Disease; Heart Failure, Systolic; Heart Rate; Hospitalization; Humans; Ivabradine; Mortality; Quality of Life; Treatment Outcome; Ventricular Function, Left

In this, the second of two articles, we continue our evaluation of drug therapies in older adults. Having previously described the pharmacokinetic and pharmacodynamic consequences of physiological ageing, along with the challenge of appropriate prescribing, we proposed four key questions which should be considered when prescribing for this cohort of the population. Does this agent reflect the priorities of the patient? Are there alternatives - with greater efficacy, effectiveness or tolerability - that might be considered? Are the dose, frequency and formulation appropriate? How does this prescription relate to concurrent medication? We also highlighted the reliance on subgroup analysis to demonstrate the efficacy of drug therapies for older adults in osteoporosis and the underutilisation of appropriate treatments for patients with Alzheimer's disease as a result of flawed guidelines. Here we describe current drug therapies in systolic heart failure, noting the limited inclusion of older adults in key trials, while also reviewing the pharmacological treatment of orthostatic hypotension. In doing so, we advocate the intermittent use of midodrine as a first-line treatment for orthostasis in older adults, counter to the generic guidelines produced by various learned societies, but in keeping with the scant trial data available.

Topics: Age Factors; Cardiovascular Agents; Geriatrics; Heart Failure, Systolic; Humans; Hypotension, Orthostatic

The optimal management of systolic heart failure includes combination therapy to influence myocardial remodelling favourably by affecting neurohormonal activation and underlying maladaptive pathophysiological pathways. These medications include modulators of the renin-angiotensin-aldosterone system (eg, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, mineralocorticoid receptor antagonists) and β-adrenergic receptor blockers. In addition, an agent with a distinct and complementary mechanism of bradycardic action, the selective pacemaker-current (If) inhibitor ivabradine, provides further reduction of heart rate. Also, a new drug that incorporates neprilysin inhibition combined with angiotensin receptor blockade shows incremental effectiveness. The primary goal of this review is to provide a mechanistic explanation of the complementary role of therapeutic interventions in modulating pathways leading to progressive systolic heart failure. A secondary goal is to summarize the key findings of the pivotal clinical trials that have demonstrated the efficacy of these agents in this population.

Topics: Cardiovascular Agents; Disease Management; Heart Failure, Systolic; Humans; Renin-Angiotensin System; Ventricular Remodeling

Topics: Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Cardiovascular Agents; Chronic Disease; Digoxin; Drug Combinations; Heart Failure; Heart Failure, Systolic; Humans; Hydralazine; Isosorbide Dinitrate; Ivabradine; Mineralocorticoid Receptor Antagonists

The aging population with hypertension and coronary artery disease is rapidly increasing worldwide and develops heart failure (HF). A wide range of pharmacotherapeutic drugs are recommended in the HF management guidelines. For the most part, these recommendations are based on the results of studies in the younger population, and most drugs were not adequately tested in the elderly. However, many changes that occur during the aging process affect the response to several of the recommended therapeutic drugs. Physicians will be increasingly involved in managing the expanding elderly population with HF. It is therefore imperative that they recognize ways to use current pharmacotherapeutic agents and the increasing need for novel agents for optimizing the management of the elderly patient with HF.

Topics: Adrenergic beta-Antagonists; Aged; Aging; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Agents; Disease Management; Diuretics; Female; Heart Failure, Systolic; Humans; Male; Mineralocorticoid Receptor Antagonists

Chronic heart failure is a common public health problem. The disease has a poor prognosis with high mortality rate and the incidence increases continuously. Prognosis of chronic systolic heart failure can be improved by several different medications as well as by special cardiac interventions based on the newly-published European and American guidelines. In case of severe systolic dysfunction, hospitalization and mortality can be reduced using angiotensin converting enzyme inhibitors, angiotensin receptor blocking drugs, beta-receptor blocking agents and aldosterone antagonists, as evidenced in multicentric studies. In selected cases different cardiac interventions, such as intracardial defibrillator and/or cardiac desynchronization device implantation can be used for supporting the failing left ventricle. In terminal stage, special devices (ventricular assist device, intra-aortic balloon pump, arteficial heart) and, finally, heart transplantation can be applied. In this paper, the authors highlight therapeutic options of chronic systolic heart failure referring to recommendations of the latest, 2012 guideline from the European Society of Cardiology.

Topics: Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Arrhythmias, Cardiac; Cardiovascular Agents; Chronic Disease; Digitalis Glycosides; Diuretics; Heart Failure, Systolic; Heart-Assist Devices; Humans; Mineralocorticoid Receptor Antagonists; Pacemaker, Artificial; Severity of Illness Index; Thromboembolism; Vasodilator Agents; Ventricular Dysfunction, Left

Heart failure (HF) is a complex syndrome characterized by the inability of the heart to maintain a normal cardiac output without elevated intracardiac filling pressures, resulting in signs of pulmonary and peripheral edema and symptoms of dyspnea and fatigue. Central to the management of HF is a multifaceted pharmacological intervention to abate the harmful counter-regulatory effects of neurohormonal activation and avid salt and water retention. Whereas up to 40 years ago HF was managed with diuretics and leaf of digitalis, the cornerstones of therapy for HF patients with systolic dysfunction now include ACE inhibitors or angiotensin II type 1 receptor antagonists (angiotensin receptor blockers), β-adrenoceptor antagonists (β-blockers), and aldosterone antagonists, which have significantly improved survival. However, with the increasing number of beneficial therapies, there are challenges to implementing all of them. Specific cardiomyopathies also merit specific considerations with respect to treatment, and - unfortunately - there is no therapy for HF with preserved left ventricular ejection fraction that has been shown to improve survival. Although mortality has improved in HF, the biggest challenge to treatment lies in addressing the morbidity of this disease, which is now the most common reason for hospital admission in our aged population. As such, there are many therapies that may serve to improve the quality of life of HF patients. Future HF treatment regimens may include direct cellular therapy via hormone and cytokine signaling or cardiac regeneration through growth factors or cell therapy.

Topics: Animals; Cardiovascular Agents; Chronic Disease; Heart Failure, Diastolic; Heart Failure, Systolic; Hospitalization; Humans

Heart failure is a major health problem and its prevalence is growing, primarily as a consequence of the aging of the population. Recently, we have witnessed significant progress in reducing the mortality associated with chronic heart failure due to the introduction of renin-angiotensin-aldosterone system inhibitors, beta-blocking agents and the use of electrical devices. However, the prognosis of heart failure is still so disappointing that it remains the leading cause of death in developed countries. This grim record impels the search for new therapeutic strategies. The objective of this paper is to briefly review the results of some recent trials that have been put in place to test the effects of drugs that are deemed to be potentially capable of improving the prognosis of chronic systolic heart failure patients. Despite compelling theoretical premises, the results to date appear to be weak or even disappointing.

Topics: Cardiovascular Agents; Chronic Disease; Evidence-Based Medicine; Heart Failure, Systolic; Humans; Treatment Outcome

To review relevant literature supporting the use of β-blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), diuretics, digoxin, aldosterone antagonists, and vasodilators in the management of heart failure in an elderly patient population aged ≥65 years.. PubMed, EMBASE, and MEDLINE searches (January 1960-April 2010) were utilized to identify primary literature using the key terms heart failure, treatment, and elderly. Additionally, reference citations from publications identified were utilized, as well as the American College of Cardiology/American Heart Association (ACC/AHA) Guidelines for the Diagnosis and Management of Chronic Heart Failure in the Adult.. Primary and tertiary literature, including subgroup analyses, published in English and relating to the use of pharmacotherapy in the treatment of systolic heart failure in the elderly was reviewed.. The aging of the US population is creating a higher prevalence of systolic heart failure in the elderly. Most clinical trials have established the mortality and morbidity benefit of pharmacotherapy in heart failure in nonelderly patients; however, the current ACC/AHA guidelines do not clearly delineate this benefit in persons ≥65 years of age.. Clinical trial data, based on limited numbers of individuals aged ≥65 years, suggest that use of β-blockers, ACE inhibitors, ARBs, aldosterone antagonists, and vasodilators (hydralazine/nitrates) have similar mortality benefit to that observed in younger patients. As supported in the ACC/AHA guidelines, these agents should be prescribed with clinical judgment to all elderly patients, with close monitoring for adverse events. Future clinical trials with greater inclusion of patients ≥65 years will help to elucidate the magnitude of benefits of optimal pharmacotherapy on mortality and morbidity rates in this population.

Topics: Adrenergic beta-Antagonists; Age Factors; Aged; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cardiotonic Agents; Cardiovascular Agents; Digoxin; Diuretics; Evidence-Based Medicine; Heart Failure, Systolic; Humans; Mineralocorticoid Receptor Antagonists; Vasodilator Agents

Topics: Aged; Cardiovascular Agents; Diagnosis, Differential; Disease Management; Exercise; Female; Heart Failure, Diastolic; Heart Failure, Systolic; Humans; Prognosis

Evidence-based management of chronic systolic heart failure includes risk factor management, therapeutic lifestyle changes, and a polypharmaceutical regimen that prolongs survival, reduces or reverses progression of myocardial dysfunction, alleviates symptoms, and limits complications. Subspecialty consultation is warranted when symptoms progress despite standard therapy; interventions are needed for refractory coronary disease, an arrhythmia device is indicated, or surgical intervention or transplantation is considered.

Topics: Ambulatory Care; Cardiology; Cardiovascular Agents; Chronic Disease; Evidence-Based Practice; Heart Failure, Systolic; Humans; Referral and Consultation; Risk Reduction Behavior

Systolic heart failure is a feed-forward phenomenon with devastating consequences. Impaired cardiac function is the initiating event, but central nervous system mechanisms activated by persistent altered neural and humoral signals from the periphery play an important sustaining role. Animals with experimentally induced heart failure have neurochemical abnormalities in the brain that, when manipulated, profoundly affect sympathetic drive, volume regulation, and cardiac remodeling--critical determinants of outcome. This brief review explores recent studies that provide a strong rationale for the development of pharmaceutical agents that target central nervous system abnormalities in heart failure.

Topics: Aldosterone; Angiotensins; Animals; Blood-Brain Barrier; Brain; Cardiovascular Agents; Cell Communication; Cytokines; Drug Carriers; Drug Design; Heart Failure, Systolic; Humans; Inflammation; Sympathetic Nervous System

Topics: Cardiovascular Agents; Heart Failure, Systolic; Humans; Life Style; Nursing Assessment; Practice Guidelines as Topic

To prove the efficacy of drugs in patients with chronic systolic heart failure, taking into consideration certain criteria is necessary for the planning and performance of the clinical investigation of medicinal products. For the different stages and the collective of patients those criteria include the definition of the corresponding endpoints, adequate study design, appropriate randomisation, blinding, the choice of an appropriate dose, valid methods of examination, the correct sample size estimation and analysis. If these criteria will b e used, the besttherapy for the different stages can be ascertained.

Topics: Cardiovascular Agents; Chronic Disease; Clinical Trials as Topic; Data Collection; Dose-Response Relationship, Drug; Double-Blind Method; Endpoint Determination; Heart Failure, Systolic; Humans; Random Allocation; Randomized Controlled Trials as Topic; Research Design

Ivabradine has potent actions in reducing heart rate and improving clinical outcomes of chronic heart failure with reduced ejection fraction (HFrEF). At present, only the short-acting formulation of ivabradine is available that needs to be administered twice daily.. This study sought to evaluate the role of ivabradine hemisulfate sustained release (SR), a novel long-acting formulation of ivabradine dosed once daily, in stable patients with HFrEF.. Patients with stabilized HFrEF in New York Heart Association functional class II-IV were enrolled and randomized to receive placebo or ivabradine SR in addition to standard medications. The primary endpoint was the change of left ventricular (LV) end-systolic volume index from baseline to week 32.. We randomly assigned 181 patients to placebo and 179 patients to ivabradine SR. After 32 weeks, a significant improvement of LV end-systolic volume index from baseline was observed in both arms with a greater effect in the ivabradine SR arm. Ivabradine SR therapy also exhibited superiority in improving LV end-diastolic volume index, LV ejection fraction, resting heart rate, the Kansas City Cardiomyopathy Questionnaire score, and hospital admission for heart failure worsening and cardiovascular disease in comparison to placebo. Overall adverse events showed no difference between the treatment arms. There were fewer occurrences of worsening heart failure in the ivabradine SR arm.. The present study demonstrates that ivabradine SR once daily in addition to optimum standard therapy improved heart function in patients with HFrEF. (Clinical Trial of Systolic Heart Failure Treatment of IvabRadine Hemisulfate Sustained-release Tablets [FIRST]; NCT02188082).

Topics: Benzazepines; Cardiovascular Agents; Delayed-Action Preparations; Double-Blind Method; Heart Failure; Heart Failure, Systolic; Heart Rate; Humans; Ivabradine; Stroke Volume; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left

Depression is often comorbid in patients with heart failure (HF) and is associated with worse clinical outcomes. However, depression generally goes unrecognized and untreated in this population.. To determine whether a blended collaborative care program for treating both HF and depression can improve clinical outcomes more than collaborative care for HF only and physicians' usual care (UC).. This 3-arm, single-blind, randomized effectiveness trial recruited 756 participants with HF with reduced left ventricular ejection fraction (<45%) from 8 university-based and community hospitals in southwestern Pennsylvania between March 2014 and October 2017 and observed them until November 2018. Participants included 629 who screened positive for depression during hospitalization and 2 weeks postdischarge and 127 randomly sampled participants without depression to facilitate further comparisons. Key analyses were performed November 2018 to March 2019.. Separate physician-supervised nurse teams provided either 12 months of collaborative care for HF and depression ("blended" care) or collaborative care for HF only (enhanced UC [eUC]).. The primary outcome was mental health-related quality of life (mHRQOL) as measured by the Mental Component Summary of the 12-item Short Form Health Survey (MCS-12). Secondary outcomes included mood, physical function, HF pharmacotherapy use, rehospitalizations, and mortality.. Of the 756 participants (mean [SD] age, 64.0 [13.0] years; 425 [56%] male), those with depression reported worse mHRQOL, mood, and physical function but were otherwise similar to those without depression (eg, mean left ventricular ejection fraction, 28%). At 12 months, blended care participants reported a 4.47-point improvement on the MCS-12 vs UC (95% CI, 1.65 to 7.28; P = .002), but similar scores as the eUC arm (1.12; 95% CI, -1.15 to 3.40; P = .33). Blended care participants also reported better mood than UC participants (Patient-Reported Outcomes Measurement Information System-Depression effect size, 0.47; 95% CI, 0.28 to 0.67) and eUC participants (0.24; 95% CI, 0.07 to 0.41), but physical function, HF pharmacotherapy use, rehospitalizations, and mortality were similar by both baseline depression and randomization status.. In this randomized clinical trial of patients with HF and depression, telephone-delivered blended collaborative care produced modest improvements in mHRQOL, the primary outcome, on the MCS-12 vs UC but not eUC. Although blended care did not differentially affect rehospitalization and mortality, it improved mood better than eUC and UC and thus may enable organized health care systems to provide effective first-line depression care to medically complex patients.. ClinicalTrials.gov Identifier: NCT02044211.

Topics: Affect; Aftercare; Cardiovascular Agents; Delivery of Health Care, Integrated; Depression; Female; Heart Failure, Systolic; Humans; Male; Middle Aged; Mortality; Patient Readmission; Patient Reported Outcome Measures; Physical Functional Performance; Quality of Life; Single-Blind Method; Telemedicine; Treatment Outcome

In the Systolic Heart failure treatment with the I. A Markov model was developed to assess the impact of ivabradine on mean survival and quality of life over a patient's lifetime (10 years). The hospitalisation and death rates were calculated using patient-level data from SHIFT. The reduction in quality of life due to HF hospitalisations was estimated directly from EQ-5D data collected in SHIFT. Australian costs were applied to the resource use from SHIFT.. The modelled mean increase in survival with ivabradine was 0.115 years. The mean increase in quality-adjusted survival was 0.108 years. The average cost of ivabradine was A$2,957 and the cost savings associated with a reduction in HF hospitalisations was A$1,344. The cost per quality adjusted life year gained (QALYG) was A$14,905. The conservative approach to the modelled evaluation, as well as results of the sensitivity analysis, demonstrates that ivabradine is likely to be cost-effective in this indication.. The conservative approach to the modelled evaluation, as well as results of the sensitivity analysis, demonstrates that ivabradine is a cost-effective treatment in the Australian setting for HF patients with a HR≥77 bpm on optimal standard therapy with a cost per QALYG similar or lower than that for other publicly funded treatments.

Topics: Cardiovascular Agents; Cost-Benefit Analysis; Female; Health Care Costs; Heart Failure, Systolic; Humans; Ivabradine; Male; Quality of Life; Quality-Adjusted Life Years; Treatment Outcome

In heart failure (HF) with reduced ejection fraction and sinus rhythm, heart rate reduction with ivabradine reduces the composite incidence of cardiovascular death and HF hospitalization.. It is unclear whether the duration of HF prior to therapy independently affects outcomes and whether it modifies the effect of heart rate reduction. In SHIFT, 6505 patients with chronic HF (left ventricular ejection fraction of ≤35%), in sinus rhythm, heart rate of ≥70 b.p.m., treated with guideline-recommended therapies, were randomized to placebo or ivabradine. Outcomes and the treatment effect of ivabradine in patients with different durations of HF were examined. Prior to randomization, 1416 ivabradine and 1459 placebo patients had HF duration of ≥4 weeks and <1.5 years; 836 ivabradine and 806 placebo patients had HF duration of 1.5 years to <4 years, and 989 ivabradine and 999 placebo patients had HF duration of ≥4 years. Patients with longer duration of HF were older (62.5 years vs. 59.0 years; P < 0.0001), had more severe disease (New York Heart Association classes III/IV in 56% vs. 44.9%; P < 0.0001) and greater incidences of co-morbidities [myocardial infarction: 62.9% vs. 49.4% (P < 0.0001); renal dysfunction: 31.5% vs. 21.5% (P < 0.0001); peripheral artery disease: 7.0% vs. 4.8% (P < 0.0001)] compared with patients with a more recent diagnosis. After adjustments, longer HF duration was independently associated with poorer outcome. Effects of ivabradine were independent of HF duration.. Duration of HF predicts outcome independently of risk indicators such as higher age, greater severity and more co-morbidities. Heart rate reduction with ivabradine improved outcomes independently of HF duration. Thus, HF treatments should be initiated early and it is important to characterize HF populations according to the chronicity of HF in future trials.

Topics: Cardiovascular Agents; Dose-Response Relationship, Drug; Double-Blind Method; Female; Follow-Up Studies; Heart Failure, Systolic; Heart Rate; Hospitalization; Humans; Ivabradine; Male; Middle Aged; Stroke Volume; Time Factors; Treatment Outcome; Ventricular Function, Left

The 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.. SHIFT 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.. ChD 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.

Topics: Argentina; Brazil; Cardiovascular Agents; Chagas Disease; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Heart Failure, Systolic; Heart Rate; Humans; Ivabradine; Male; Middle Aged; Stroke Volume; Survival Rate; Treatment Outcome; Ventricular Function, Left

The aim of this article is to discuss methods used to analyze health-related quality of life (HRQoL) data from randomized controlled trials (RCTs) for decision analytic models. The analysis presented in this paper was used to provide HRQoL data for the ivabradine health technology assessment (HTA) submission in chronic heart failure.. We have used a large, longitudinal EuroQol five-dimension questionnaire (EQ-5D) dataset from the Systolic Heart Failure Treatment with the I. Ivabradine was associated with an HRQoL weight gain of 0.01. HRQoL weights differed according to New York Heart Association (NYHA) class (NYHA I-IV, no hospitalization: standard care 0.82-0.46; ivabradine 0.84-0.47). A reduction in HRQoL weight was associated with hospitalizations within 30 days of an HRQoL assessment visit, with this reduction varying by NYHA class [-0.07 (NYHA I) to -0.21 (NYHA IV)].. The mixed model explained variation in EQ-5D data according to key clinical outcomes and patient characteristics, providing essential information for long-term predictions of patient HRQoL in the cost-effectiveness model. This model was also used to estimate the loss in HRQoL associated with hospitalizations. In SHIFT many hospitalizations did not occur close to EQ-5D visits; hence, any temporary changes in HRQoL associated with such events would not be captured fully in observed RCT evidence, but could be predicted in our cost-effectiveness analysis using the mixed model. Given the large reduction in hospitalizations associated with ivabradine this was an important feature of the analysis.. The Servier Research Group.

Topics: Aged; Benzazepines; Cardiovascular Agents; Cost-Benefit Analysis; Female; Heart Failure, Systolic; Hospitalization; Humans; Ivabradine; Male; Middle Aged; Models, Statistical; Quality of Life; Severity of Illness Index; Surveys and Questionnaires

During the post-discharge phase following a heart failure hospitalization (HFH), patients are at high risk of early readmission despite standard of care therapy. We examined the impact of chronic exposure to ivabradine on early readmissions in patients hospitalized for heart failure during the course of the SHIFT study (Systolic Heart Failure treatment with the If inhibitor ivabradine Trial).. A total of 1186 of the 6505 randomized patients experienced at least one HFH during the study, and had a more severe profile than those without HFH. Of these 1186 patients, 334 patients (28%) were rehospitalized within 3 months for any reason, mostly for cardiovascular causes (86%), including HFH (61%). Ivabradine was associated with fewer all-cause hospitalizations at 1 month [incidence rate ratio (IRR) 0.70, 95% confidence interval (CI) 0.50-1.00, P < 0.05], 2 months (IRR 0.75, 95% CI 0.58-0.98, P = 0.03), and 3 months (IRR 0.79, 95% CI 0.63-0.99, P = 0.04). A trend for a reduction in cardiovascular and HF hospitalizations was also observed in ivabradine-treated patients.. We demonstrate in this post-hoc analysis that chronic exposure to ivabradine reduces the incidence of all-cause hospitalizations during the vulnerable phase after a HFH. Further studies are needed to investigate if in-hospital or early post-discharge initiation of ivabradine could be useful to improve early outcomes in patients hospitalized for HF.

Topics: Aged; Benzazepines; Cardiovascular Agents; Disease Progression; Double-Blind Method; Female; Heart Failure, Systolic; Hospitalization; Humans; Ivabradine; Male; Middle Aged; Patient Readmission; Treatment Outcome

Heart rate (HR) reduction is associated with improved outcomes in patients with heart failure (HF) and biomarkers can be a valuable diagnostic tool in HF management. The primary aim of our study was to evaluate the short-term (6 months) effect of ivabradine on N-terminal pro B-type natriuretic peptide (NT-proBNP), CA-125, and cystatin-C values in systolic HF outpatients, and secondary aim was to determine the relationship between baseline HR and the NT-proBNP, CA-125, cystatin-C, and clinical status variation with ivabradine therapy.. Ninety-eight patients (mean age: 65.81 ± 10.20 years; 33 men), left ventricular ejection fraction < 35% with Simpson method, New York Heart Association (NYHA) class II-III, sinus rhythm and resting HR > 70/min, optimally treated before the study were included. Among them, two matched groups were formed: the ivabradine group and the control group. Patients received ivabradine with an average (range of 10-15) mg/day during 6 months of follow-up. Blood samples for NT-proBNP, CA-125, and cystatin-C were taken at baseline and at the end of a 6-month follow-up in both groups.. There was a significant decrease in NYHA class in the ivabradine group (2.67 ± ± 0.47 vs. 1.85 ± 0.61, p < 0.001). When ivabradine and control groups were compared, a significant difference was also found in NHYA class 6 months later (p = 0.013). A significant decrease was found in HR in the ivabradine and control groups (84.10 ± 8.76 vs. 68.36 ± ± 8.32 bpm, p = 0.001; 84.51 ± 10 vs. 80.40 ± 8.3 bpm, p = 0.001). When both groups were compared, a significant difference was also found in HR after 6 months (p = 0.001). A significant decrease was found in cystatin-C (2.10 ± 0.73 vs. 1.50 ± 0.44 mg/L, p < 0.001), CA-125 (30.09 ± 21.08 vs. 13.22 ± 8.51 U/mL, p < 0.001), and NT-proBNP (1,353.02 ± 1,453.77 vs. 717.81 ± 834.76 pg/mL, p < 0.001) in the ivabradine group. When ivabradine and control groups were compared after 6 months, a significant decrease was found in all HF parameters (respectively; cystatin-C: p = 0.001, CA-125: p = 0.001, NT-proBNP: p = 0.001). Creatinine level was significantly decreased and glomerular filtration rate (GFR) was significantly increased in the ivabradine group (1.02 ± 0.26 vs. 0.86 ± 0.17, creatinine: p = 0.001; 79.26 ± 18.58 vs. 92.48 ± 19.88, GFR: p = 0.001). There was no significant correlation between NYHA classes (before and after ivabradine therapy) and biochemical markers, or HR.. In the outpatients with systolic HF, persistent resting HF > 70/min with optimal medical therapy, the NT-proBNP, CA-125, and cystatin-C reductions were obtained with ivabradine treatment. Measurement of NT-proBNP, CA-125, and cystatin-C may prove to be useful in biomarker panels evaluating ivabradine therapy response in HF patients.

Topics: Aged; Benzazepines; Biomarkers; CA-125 Antigen; Cardiovascular Agents; Cystatin C; Down-Regulation; Female; Heart Failure, Systolic; Heart Rate; Humans; Ivabradine; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Stroke Volume; Time Factors; Treatment Outcome; Turkey; Ventricular Function, Left

We explored the prescription of β-blockers with ivabradine in patients with systolic heart failure, focusing on the most frequently coprescribed β-blocker, carvedilol.. We analyzed outcomes in SHIFT patients with systolic heart failure who were prescribed β-blockers (carvedilol, bisoprolol, metoprolol, or nebivolol) with ivabradine or placebo. Analysis was by intention to treat in patients prescribed a β-blocker at the time of the event.. Data were available for 2,596 patients receiving carvedilol, 1,483 bisoprolol, 1,424 metoprolol, and 197 nebivolol. Mean treatment duration was 19 months. There was no difference in the effect of ivabradine on the primary composite endpoint of cardiovascular death or heart failure hospitalization between the various β-blockers [hazard ratios (HR) for risk reduction, 0.75-0.89; p for interaction=0.86]. Patients prescribed carvedilol with ivabradine had lower rates of primary composite endpoint (HR 0.80, 95% CI: 0.68-0.94), heart failure hospitalization (HR 0.73, 95% CI: 0.61-0.88), and cardiovascular hospitalization (HR 0.80, 95% CI: 0.69-0.92) versus carvedilol with placebo. The dosage of carvedilol had no detectable effect and there were no unexpected safety issues.. Whatever β-blocker was coprescribed with ivabradine, there were improvements in cardiovascular outcomes in patients with systolic heart failure, especially with the most prescribed β-blocker--carvedilol.

Topics: Adrenergic beta-Antagonists; Aged; Benzazepines; Bisoprolol; Carbazoles; Cardiovascular Agents; Carvedilol; Double-Blind Method; Drug Therapy, Combination; Female; Heart Failure, Systolic; Hospitalization; Humans; Ivabradine; Male; Metoprolol; Middle Aged; Nebivolol; Propanolamines; Proportional Hazards Models; Treatment Outcome

Ivabradine, a specific heart rate lowering agent, was shown in the SHIFT study to reduce time to first hospitalization for worsening heart failure (HF) in chronic systolic HF patients and also to reduce recurrent/total hospitalizations over the study interval. We assessed the effects of adding ivabradine in patients with systolic HF on the number needed to treat (NNT) to reduce recurrent hospitalizations.. The SHIFT trial included 6505 patients with symptomatic HF (NYHA II-IV), left ventricular ejection fraction ≤35% and heart rate ≥70 bpm in sinus rhythm. Patients were randomized to either ivabradine or placebo in addition to guidelines-based drug therapy. The times to first hospitalization were analyzed using a univariate Cox proportional-hazards model; the associated NNT was calculated using Kaplan-Meier estimates of the time-to-event curves at 1 year in each treatment arm. Recurrent hospitalizations were analyzed using a negative binomial and the estimated annual event rates used to calculate the associated patient-time NNTs respectively.. The estimated NNT (number needed to initiate treatment with ivabradine to prevent one first HF hospitalization within 1 year) was 27 (estimated hazard ratio: 0.75, P < 0.0001). For recurrent HF hospitalizations, one event would be prevented on average per 14 patient-years for any year of follow-up over the course of SHIFT (estimated rate ratio: 0.71, P < 0.0001). A key limitation of this analysis is that it did not account for a relationship between recurrent HF hospitalizations and subsequent mortality.. In chronic systolic HF the effect of ivabradine on reducing recurrent HF hospitalizations results in a lower NNT compared to the effect on the time for first hospitalization. The effect of ivabradine on recurrent hospitalizations, in addition to first events, may be a more appropriate measure when considering the impact of a treatment with ivabradine on healthcare resource utilization.

Topics: Benzazepines; Cardiovascular Agents; Chronic Disease; Heart Failure, Systolic; Heart Rate; Hospitalization; Humans; Ivabradine; Numbers Needed To Treat; Proportional Hazards Models; Treatment Outcome

Incidence of chronic heart failure (HF) increases with age and cardiovascular (CV) morbidity. Co-morbidities increase hospitalization and mortality in HF, and non-CV co-morbidities may lead to preventable hospitalizations. We studied the impact of co-morbidities on mortality and morbidity in Systolic Heart Failure Treatment with the I(f) Inhibitor Ivabradine Trial, and investigated whether the impact of ivabradine was affected by co-morbidities. We analyzed the Systolic Heart Failure Treatment with the I(f) Inhibitor Ivabradine Trialpopulation, with moderate-to-severe HF and left ventricular dysfunction (in sinus rhythm with heart rate at rest ≥70 beats/min), according to co-morbidity: chronic obstructive pulmonary disease, diabetes mellitus, anemia, stroke, impaired renal function, myocardial infarction, hypertension, and peripheral artery disease. Co-morbidity load was classed as 0, 1, 2, 3, 4+ or 1 to 2 co-morbidities, or 3+ co-morbidities. Co-morbidities were evenly distributed between the placebo and ivabradine groups. Patients with more co-morbidities were likely to be older, women, had more advanced HF, were less likely to be on β blockers, with an even distribution on ivabradine 2.5, 5, or 7.5 mg bid and placebo at all co-morbidity loads. Number of co-morbidities was related to outcomes. Cardiovascular death or HF hospitalization events significantly increased (p <0.0001) with co-morbidity load, with the most events in patients with >3 co-morbidities for both, ivabradine and placebo. There was no interaction between co-morbidity load and the treatment effects of ivabradine. Hospitalization rate was lower at all co-morbidity loads for ivabradine. In conclusion, cardiac and noncardiac co-morbidities significantly affect CV outcomes, particularly if there are >3 co-morbidities. The effect of heart rate reduction with ivabradine is maintained at all co-morbidity loads.

Topics: Aged; Benzazepines; Cardiovascular Agents; Comorbidity; Cyclic Nucleotide-Gated Cation Channels; Double-Blind Method; Female; Follow-Up Studies; Global Health; Heart Failure, Systolic; Heart Rate; Humans; Incidence; Ivabradine; Male; Middle Aged; Myocardial Infarction; Pulmonary Disease, Chronic Obstructive; Survival Rate; Treatment Outcome

Low systolic blood pressure (SBP) is associated with poor outcomes in heart failure and complicates management. In a post hoc analysis, we investigated the efficacy and safety of ivabradine in the SHIFT population divided by tertiles of baseline SBP.. The analysis comprised 2110 patients with SBP <115 mmHg, 1968 with 115≤ SBP <130 mmHg, and 2427 with SBP ≥130 mmHg. Patients with low SBP were younger, had lower ejection fraction, and were less likely to be at target beta-blocker dose than patients in the other SBP groups. Ivabradine was associated with a similar relative risk reduction of the composite outcome in the three SBP groups [SBP <115 mmHg, hazard ratio (HR) = 0.84, 95% confidence interval (CI) 0.72-0.98; 115≤ SBP <130 mmHg, HR = 0.86, 95% CI 0.72 to 1.03; SBP ≥130 mmHg, HR = 0.77, 95% CI 0.66 to 0.92; P interaction = 0.68]. Similar results were found for cardiovascular mortality (P interaction = 0.91), hospitalization because of heart failure (P interaction = 0.79), all-cause mortality (P interaction = 0.90), and heart failure mortality (P interaction = 0.18). There was no evidence for a difference in safety profile according to SBP group.. The efficacy and safety of ivabradine is independent of SBP. This may have implications for the management of HF patients with low SBP and elevated heart rate.

Topics: Aged; Benzazepines; Blood Pressure; Cardiovascular Agents; Double-Blind Method; Female; Heart Failure, Systolic; Humans; Hypertension; Hypotension; Ivabradine; Male; Middle Aged; Prognosis; Systole; Treatment Outcome

We explored the impact of being hospitalized due to worsening heart failure (WHF) or a myocardial infarction (MI) on subsequent mortality in a large contemporary data set of patients with stable chronic systolic heart failure (HF).. A total of 6558 patients with stable systolic HF, 6505 with analysable data, with an EF of ≤35%, who were included in the Systolic Heart failure treatment with the If inhibitor ivabradine Trial (SHIFT), were followed for a median of 22.9 months with respect to hospitalizations and vital status. Among the 1288 patients who had at least one hospitalization due to WHF or MI, 455 (35.3%) died during follow-up compared with 600 (11.5%) among patients not hospitalized for these reasons. The risk for death was highest in the early phase after hospitalization. The risk declined rapidly during the first month but remained 3.5-fold (95% confidence interval 2.3-5.1) increased at 18 months after a first WHF hospitalization and 8.8-fold (95% confidence interval 3.6-21.6) increased at 18 months after a first MI hospitalization.. The present study confirms previous findings that in patients with stable chronic systolic HF, a hospitalization for WHF or MI is associated with substantially increased risk for subsequent death even with contemporary extensive background pharmacological therapy. The risk is most pronounced in the early phase of hospitalization but remains elevated even after 18 months. Preventing HF hospitalization appears as an important therapeutic objective in such patients, and a hospitalization for WHF or MI should lead to a careful therapeutic reassessment.

Topics: Aged; Aged, 80 and over; Benzazepines; Cardiovascular Agents; Chronic Disease; Disease Progression; Female; Follow-Up Studies; Heart Failure, Systolic; Hospitalization; Humans; Ivabradine; Male; Middle Aged; Myocardial Infarction; Prognosis; Risk Factors; Time Factors

This study was designed to evaluate a new NT-proBNP monitoring concept in outpatients with systolic heart failure (HF).. This was a multicentre, prospective randomized open-label blinded endpoint study. A total of 407 systolic HF patients were allocated to either clinical management (n = 208) or clinical management + NT-proBNP monitoring (n = 199) and followed for 2.5 years. If NT-proBNP increased >30%, a clinical checklist was completed and treatment initiated. The patients were matched at randomization and were 73 years old, 25% were females, 85% were NYHA class I-II, LVEF was 30%, and NT-proBNP 1955 pg/mL. NT-proBNP monitoring did not improve outcome, the hazard ratio for the primary composite endpoint (death or a cardiovascular admission) being 0.96 [95% confidence interval (CI) 0.71-1.29, P = 0.766]. NT-proBNP monitoring did not induce a significant change in the pharmacological strategy (P > 0.05 for all comparisons). In patients in whom NT-proBNP increased >30% (25% of the patients) during follow-up, a higher frequency of admission (69% vs. 47%, P = 0.002), a higher number of admission days (14 vs. 5 days, P = 0.003) and number of admissions (2 vs. 1, P = 0.009), and a lower quality of life (P = 0.032) and a poorer functional class (37% vs. 18% in NYHA class III-IV, P < 0.001) were observed.. Adding serial measurements of NT-proBNP to optimal clinical management was not associated with a change in pharmacological strategy and did not improve outcome. However, survivors in whom NT-proBNP increased >30% showed a poorer functional class, clinical outcome, and quality of life.. www.centerwatch: 173491 (NorthStar).

Topics: Aged; Aged, 80 and over; Biomarkers; Cardiac Output; Cardiovascular Agents; Double-Blind Method; Female; Follow-Up Studies; Heart Failure, Systolic; Hospitalization; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Outpatients; Peptide Fragments; Prognosis; Prospective Studies; Registries; Severity of Illness Index

Over the last few years, the use of phosphodiesterase type 5 (PDE5) inhibitors has been expanded to management of various cardiovascular disorders beyond pulmonary arterial hypertension. This study is designed to investigate the ability of udenafil, a newly developed long-acting PDE5 inhibitor, to improve functional capacity and hemodynamic status in a cohort of chronic systolic heart failure (SHF) patients.. Stable, chronic SHF patients will be randomly assigned to placebo (26 patients) or udenafil at a dose of 50 mg twice per day (26 patients) for the first 4 weeks followed by 100 mg twice daily for the next 8 weeks. Eligibility criteria will be age ≥ 18 years, clinical diagnosis of chronic SHF with current New York Heart Association class II to IV symptoms, left ventricular ejection fraction ≤ 40%, and experience of at least one of following during the 12 months prior to study entry: hospitalization for decompensated heart failure, acute treatment with intravenous loop diuretics or hemofiltration, or pulmonary artery systolic pressure ≥ 40 mmHg on transthoracic echocardiography. Pharmacological therapy for SHF will be optimized in all patients at least 30 days before study entry. The primary outcome will be the change of maximal oxygen uptake, assessed by cardiopulmonary exercise testing. Secondary outcomes will include changes in ventilatory efficiency (minute ventilation/carbon dioxide production slope), left ventricular systolic and diastolic parameters, pulmonary artery systolic pressure, plasma concentration of brain natriuretic peptide, occurrence of mortality or hospitalization for heart failure, and the occurrence of any adverse event.. Unique identifier: NCT01646515.

Topics: Biomarkers; Cardiovascular Agents; Chronic Disease; Clinical Protocols; Double-Blind Method; Drug Administration Schedule; Exercise Test; Exercise Tolerance; Heart Failure, Systolic; Hemodynamics; Hospitalization; Humans; Natriuretic Peptide, Brain; Oxygen Consumption; Phosphodiesterase 5 Inhibitors; Prospective Studies; Pyrimidines; Recovery of Function; Republic of Korea; Research Design; Stroke Volume; Sulfonamides; Systole; Time Factors; Treatment Outcome; Ventricular Function, Left

Despite the current drug and device therapies, heart failure remains associated with high rates of disability, morbidity, and mortality. There is a need for newer therapies. One investigational approach is the use of ventricular support devices. These devices reduce ventricular wall stress leading to decreases in left ventricular (LV) volumes, dimensions, and mass. Ventricular support devices have been shown to reverse pathological ventricular remodeling, improve systolic function, and improve symptoms of heart failure. The Prospective Evaluation of Elastic Restraint to LESSen the effects of Heart Failure (PEERLESS-HF) trial was designed to further evaluate the safety and efficacy of one such device, the HeartNet (Paracor Medical, Sunnyvale, CA).. The HeartNet is an elastic ventricular restraint device formed from nitinol and covered in silicone, implanted using a minimally invasive approach. The aim of this randomized controlled trial is to compare optimal heart failure drug and device therapy plus the HeartNet (treatment group) to optimal drug and device therapy alone (control group) in patients with advanced systolic heart failure (LV ejection fraction ≤35% and LV end diastolic diameter <85 mm). Primary efficacy end points include the change in peak VO(2), quality of life score, and 6-minute hall walk distance from baseline to 6 months. The primary safety objective is to demonstrate noninferiority for all-cause mortality at 12 months. Planned enrollment is for 272 patients at approximately 35 centers in North America.. The PEERLESS-HF trial will evaluate the safety and efficacy of ventricular elastic support in advanced systolic heart failure, advancing our knowledge of this investigational approach to heart failure therapy.

Topics: Adult; Aged; Cardiovascular Agents; Exercise Tolerance; Female; Heart Failure, Systolic; Heart-Assist Devices; Humans; Male; Middle Aged; North America; Oxygen; Patient Selection; Prospective Studies; Quality of Life; Research Design; Safety; Severity of Illness Index; Stroke Volume; Thoracotomy; Time Factors; Treatment Outcome; Ventricular Remodeling; Walking

Heart failure (HF) treatment guided by amino-terminal pro-B type natriuretic peptide (NT-proBNP) may reduce cardiovascular event rates compared to standard-of-care (SOC) management. Comprehensive understanding regarding effect of NT-proBNP guided care on patient-reported quality of life (QOL) remains unknown.. One hundred fifty-one subjects with HF due to left ventricular systolic dysfunction were randomized to either SOC HF management or care with a goal to reduce NT-proBNP values ≤1000 pg/mL. Effects of HF on QOL were assessed using the Minnesota Living with HF Questionnaire (MLHFQ) quarterly, with change (Δ) in score assessed across study procedures and as a function of outcome.. Overall, baseline MLHFQ score was 30. Across study visits, QOL improved in both arms, but was more improved and sustained in the NT-proBNP arm (repeated measures P = .01); NT-proBNP patients showing greater reduction in MLHFQ score (-10.0 vs -5.0; P = .05), particularly in the physical scale of the questionnaire. Baseline MLHFQ scores did not correlate with NT-proBNP; in contrast, ∆MLHFQ scores modestly correlated with ∆NT-proBNP values (ρ = .234; P = .006) as did relative ∆ in MLHFQ score and NT-proBNP (ρ = .253; P = .003). Considered in tertiles, less improvement in MLHFQ scores was associated with a higher rate of HF hospitalization, worsening HF, and cardiovascular death (P = .001).. We describe novel associations between NT-proBNP concentrations and QOL scores among patients treated with biomarker guided care. Compared to SOC HF management, NT-proBNP guided care was associated with greater and more sustained improvement in QOL (Clinical Trial Registration: www.clinicaltrials.govNCT00351390).

Topics: Adrenergic beta-Antagonists; Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Biomarkers; Cardiovascular Agents; Chronic Disease; Digoxin; Diuretics; Female; Follow-Up Studies; Health Status; Heart Failure, Systolic; Humans; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Natriuretic Peptide, Brain; Peptide Fragments; Quality of Life; Severity of Illness Index; Surveys and Questionnaires; Treatment Outcome

Chronic (systolic) heart failure (CHF) represents a clinical syndrome with high individual and societal burden of disease. Multifaceted interventions like case management are seen as promising ways of improving patient outcomes, but lack a robust evidence base, especially for primary care. The aim of the study was to explore the effectiveness of a new model of CHF case management conducted by doctors' assistants (DAs, equivalent to a nursing role) and supported by general practitioners (GPs).. This patient-randomised controlled trial (phase II) included 31 DAs and employing GPs from 29 small office-based practices in Germany. Patients with CHF received either case management (n = 99) consisting of telephone monitoring and home visits or usual care (n = 100) for 12 months. We obtained clinical data, health care utilisation data, and patient-reported data on generic and disease-specific quality of life (QoL, SF-36 and KCCQ), CHF self-care (EHFScBS) and on quality of care (PACIC-5A). To compare between groups at follow-up, we performed analyses of covariance and logistic regression models.. Baseline measurement showed high guideline adherence to evidence-based pharmacotherapy and good patient self-care: Patients received angiotensin converting enzyme inhibitors (or angiotensin-2 receptor antagonists) in 93.8% and 95%, and betablockers in 72.2% and 84%, and received both in combination in 68% and 80% of cases respectively. EHFScBS scores (SD) were 25.4 (8.4) and 25.0 (7.1). KCCQ overall summary scores (SD) were 65.4 (22.6) and 64.7 (22.7). We found low hospital admission and mortality rates. EHFScBS scores (-3.6 [-5.7;-1.6]) and PACIC and 5A scores (both 0.5, [0.3;0.7/0.8]) improved in favour of CM but QoL scores showed no significant group differences (Physical/Mental SF-36 summary scores/KCCQ-os [95%CI]: -0.3 [-3.0;2.5]/-0.1 [-3.4;3.1]/1.7 [-3.0;6.4]).. In this sample, with little room for improvement regarding evidence-based pharmacotherapy and CHF self-care, case management showed no improved health outcomes or health care utilisation. However, case management significantly improved performance and key intermediate outcomes. Our study provides evidence for the feasibility of the case management model.. ISRCTN30822978.

Topics: Aged; Aged, 80 and over; Cardiovascular Agents; Case Management; Chronic Disease; Evidence-Based Medicine; Feasibility Studies; Female; Germany; Guideline Adherence; Heart Failure, Systolic; Hospitalization; House Calls; Humans; Logistic Models; Male; Middle Aged; Outcome and Process Assessment, Health Care; Physician Assistants; Physicians, Family; Practice Guidelines as Topic; Primary Health Care; Quality of Health Care; Quality of Life; Self Care; Telephone; Time Factors; Treatment Outcome; Workforce

The purpose of this study was to evaluate the advantage of heart rate (HR) modulation using ivabradine referring Doppler echocardiography over the conventional ivabradine therapy without echocardiography guide in patients with systolic heart failure.. From October 2020, our institute updated the protocol of ivabradine therapy, in which HR was optimized to minimize the overlap between the two left ventricular inflow waves using Doppler echocardiography (echo-guided group). The degree of cardiac reverse remodeling at 3-month follow-up was compared between the echo-guided group and the conventional ivabradine therapy group treated before October 2020.. A total of 28 patients (62 years old, 17 men) were included, and 18 patients were from echo-guided group. Left ventricular ejection fraction increased significantly in the echo-guided group (from 41% [28%, 49%] to 55% [37%, 66%], p = 0.007), whereas it remained unchanged in the conventional group (p = 0.333). Systolic blood pressure and the daily dose of carvedilol increased significantly only in the echo-guided group (p = 0.009 and p = 0.001, respectively).. Among those with systolic heart failure, a Doppler echocardiography guide might be a promising therapeutic tool in modulating HR by ivabradine in facilitating reverse remodeling.

Topics: Benzazepines; Cardiovascular Agents; Echocardiography, Doppler; Heart Failure; Heart Failure, Systolic; Heart Rate; Humans; Ivabradine; Male; Middle Aged; Stroke Volume; Ventricular Function, Left

In the SHIFT (Systolic Heart failure treatment with the I. The time to statistically significant reduction of the primary outcome (HF hospitalization and cardiovascular death) and its components, all-cause death, and HF death, were assessed in a post-hoc analysis of the SHIFT trial in the overall population (HR ≥70 bpm) and at HR ≥75 bpm, representing the approved label in many countries. Compared to placebo, the primary outcome and HF hospitalizations were significantly reduced at 102 days, while there was no effect on cardiovascular death, all-cause death, and HF death at HR ≥70 bpm. In the population with a baseline HR ≥75 bpm, a reduction of the primary outcome occurred after 67 days, HF hospitalization after 78 days, cardiovascular death after 169 days, death from HF after 157 days and all-cause death after 169 days.. Treatment with ivabradine should not be deferred in patients in sinus rhythm with a HR of ≥70 bpm to reduce the primary outcome and HF hospitalizations, in particular in patients with HR ≥75 bpm. At HR ≥75 bpm, the time to risk reduction was shorter for reduction of hospitalization and mortality outcomes in patients with HFrEF after initiation of guideline-directed medication, including beta-blockers at maximally tolerated doses.

Topics: Benzazepines; Bradycardia; Cardiovascular Agents; Heart Failure; Heart Failure, Systolic; Heart Rate; Humans; Ivabradine; Stroke Volume; Treatment Outcome

Topics: Benzazepines; Cardiovascular Agents; Heart Failure; Heart Failure, Systolic; Heart Rate; Humans; Ivabradine; Treatment Outcome

Topics: Cardiovascular Agents; Evidence-Based Medicine; Ferric Compounds; Glycosides; Heart Failure, Systolic; Hospitalization; Humans; Maltose; Randomized Controlled Trials as Topic; Recovery of Function; Research Design; Sodium-Glucose Transporter 1; Sodium-Glucose Transporter 2 Inhibitors; Stroke Volume; Treatment Outcome; Urea; Ventricular Function, Left

Topics: Adult; Aged; Ambulatory Care; Cardiovascular Agents; Exercise Tolerance; Female; Functional Status; Heart Failure, Systolic; Hospitalization; Humans; Infusions, Intravenous; Male; Middle Aged; Recovery of Function; Simendan; Stroke Volume; Time Factors; Treatment Outcome; Ventricular Function, Left

According to national guidelines and statements drugs that can cause or exacerbate heart failure (HF) are considered potentially harmful and should be avoided if possible in patients with a diagnosis of heart failure with reduced ejection fraction (HFREF). To evaluate the prevalence of potentially harmful drug (PHD) prescription among patients with a diagnosis of systolic heart failure we conducted a retrospective cohort study using Truven Health MarketScan Commercial database from 2011 to 2014. Prescription of PHD as defined by American Heart Association Statement was examined among patients with a HFREF diagnosis in: (1) Two outpatient encounters, (2) One inpatient encounter as primary diagnosis and/or (3) one inpatient encounter any position and one outpatient encounter. Among 40,966 patients, 24.2% were prescribed with at least 1 drug with the potential to cause or exacerbate heart failure. Of the 9,954 patients prescribed with PHD, nonsteroidal anti-inflammatory agents were the most frequent category prescribed (67.4%), followed by antihypertensive (24%), diabetes mellitus (23.3%), neurological and psychiatric (21%) and antiarrhythmic medications (12.6%). After multivariable analysis female patients, the presence of a comorbidity associated with a PHD use and polypharmacy were more frequently prescribed a PHD. In conclusion almost ¼ of adult patients with a diagnosis of HFREF have a prescription of a drug with a potential to cause or exacerbate heart failure as defined by current heart failure guidelines.

Topics: Adolescent; Adult; Aged; Cardiovascular Agents; Drug Prescriptions; Female; Follow-Up Studies; Heart Failure, Systolic; Humans; Male; Middle Aged; Polypharmacy; Retrospective Studies; Stroke Volume; Young Adult

The presence of concomitant erectile dysfunction (ED) with heart failure (HF) is not surprising, because endothelial dysfunction is pathophysiologic signature of both ED and HF. ED significantly and adversely affects quality of life in patients with HF. It was demonstrated that ivabradine treatment can improve endothelial function and ED in experimental models. In this study, we aimed to determine the effect of ivabradine treatment on ED in patients with HF via International Index of Erectile Function (IIEF-5) questionaire.. Consequently, 29 patients, between 18 and 70 years of age, male with chronic HF known for at least 1 year, New York Heart Association functional class I-II, left ventricule ejection fraction less than 40%, in sinus rhythm with a resting HR of at least 70 beats per minute (b.p.m.), who were intended to be treated with ivabradine according to the decision of their physicians were evaluated to determine ED. We used the Turkish version of the IIEF-5 questionnaire to evaluate ED on the last 6-month period. Twenty-four of 29 patients who scored ≤21 were considered to have ED and included to the study. IIEF-5 scores for each question and domains were calculated for all responders at baseline and at 6-month follow-up visit in order to determine any effect of ivabradine treatment on ED in patients with HF.. According to the data of survey, Cronbach's alpha coeffient for all of the patients who were included into the study were 0.84 and detected highly reliable. IEFF-5 questionnaire scores increased significantly (p = .003) after the ivabradine treatment, on the contrary, significant decrease in HR was revealed as expected. HR is decreased steadily after ivabradine treatment and mean decrease in HR was 11.5 ± 9.4 in this study population. Likewise, negative correlation was demonstrated between decrease in HR (p < .001) and increase in IEFF-5 scores (p = .003).. Although lack of patients with HF have been evaluated in this study population, initial results seem promising that ivabradine has favorable effects on ED. These findings were postulated to be dependent exclusively on HR reduction. As a sequel, cardiologist should avoid neglecting ED to improve medical compliance as well as quality of life in patients with heart failure. This pilot study provide some data for further randomized controlled studies.

Topics: Aged; Analysis of Variance; Benzazepines; Cardiovascular Agents; Echocardiography; Erectile Dysfunction; Heart Failure, Systolic; Heart Rate; Humans; Ivabradine; Male; Middle Aged; Penile Erection; Pilot Projects; Quality of Life; Surveys and Questionnaires; Turkey

Topics: Adrenergic beta-Antagonists; Cardiovascular Agents; Drug Therapy, Combination; Female; Follow-Up Studies; Heart Failure, Systolic; Heart Rate; Humans; Ivabradine; Male; Stroke Volume; Time Factors; Treatment Outcome

Ivabradine works in the sinoatrial node to prolong diastolic depolarization and reduce heart rate. In patients with chronic systolic heart failure, this drug has reduced the risk of hospitalization when used in combination with other optimal pharmacotherapy.

Topics: Benzazepines; Cardiovascular Agents; Diastole; Heart Failure, Systolic; Heart Rate; Humans; Ivabradine; Systole; Treatment Outcome

: Ivabradine is a selective and specific inhibitor of If current. With its pure negative chronotropic action, it is recommended by European Society of Cardiology and American College of Cardiology/American Heart Association guidelines in symptomatic heart failure patients (NYHA ≥ 2) with ejection fraction 35% or less, sinus rhythm and heart rate (HR) at least 70 bpm, despite maximally titrated β-blocker therapy. Data supporting this indication mainly derive from the SHIFT study, in which ivabradine reduced the combined endpoint of mortality and hospitalization, despite the fact that only 26% of patients enrolled were on optimal β-blocker doses. The aim of the present analysis is to establish the real-life eligibility for ivabradine in a population of patients with systolic heart failure, regularly attending a single heart failure clinic and treated according to guideline-directed medical therapy (GDMT). The clinical cards of 308 patients with heart failure with reduced ejection fraction (HFrEF) through a 68-month period of observation were retrospectively analyzed. GDMT, including β-blocker up-titration to maximal tolerated dose, was implemented during consecutive visits at variable intervals. Demographic, clinical and echocardiographic data were collected at each visit, together with 12-leads ECG and N-terminal pro-B-type natriuretic peptide levels. Out of 308 analyzed HFrEF patients, 220 (71%) were on effective β-blocker therapy, up-titrated to effective/maximal tolerated dose (55 ± 28% of maximal dose) (HR 67 ± 10 bpm). Among the remaining 88 patients, 10 (3.2%) were on maximally tolerated β blocker and ivabradine; 21 patients (6.8%), despite being on maximal tolerated β-blocker dose, had still HR ≥70 bpm, ejection fraction 35% or less and were symptomatic NYHA ≥2, being therefore eligible for ivabradine treatment. The remaining 57 (18%) patients were not on β blocker due to either intolerance or major contraindications. Among them, 13 (4%) were taking ivabradine alone. Of the final 44 (14%) patients, 27 (9%) showed an inadequate HR control (74 ± 6 bpm). Of these, only eight (3%) patients resulted to be eligible for ivabradine introduction according to HR and ejection fraction parameters. Overall ivabradine was indicated in 52 patients (16.8%) out of 308 enrolled.In conclusion, in a carefully managed population of patients with moderate and stable HFrEF, in which optimal GDMT is properly attained, indication to ivabradine treatment is around 17%.

Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Cardiovascular Agents; Chronic Disease; Echocardiography; Female; Heart Failure, Systolic; Heart Rate; Hospitalization; Humans; Ivabradine; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Retrospective Studies; Stroke Volume; Ventricular Function, Left

Topics: Benzazepines; Cardiovascular Agents; Heart Failure; Heart Failure, Systolic; Heart Rate; Humans; Ivabradine

Topics: Benzazepines; Cardiovascular Agents; Heart Failure; Heart Failure, Systolic; Heart Rate; Humans; Ivabradine

The sinus node inhibitor ivabradine was approved for patients with heart failure (HF) after the ivabradine and outcomes in chronic HF (SHIFT [Systolic Heart Failure Treatment With the IF Inhibitor Ivabradine Trial]) trial. Our objective was to characterize the proportion of patients with HF eligible for ivabradine and the representativeness of the SHIFT trial enrollees compared with those in the Swedish Heart Failure Registry.. We examined 26 404 patients with clinical HF from the Swedish Heart Failure Registry and divided them into SHIFT type (left ventricular ejection fraction <40%, New York Heart Association class II-IV, sinus rhythm, and heart rate ≥70 beats per minute) and non-SHIFT type. Baseline characteristics and medication use were compared and change in eligibility over time was reported at 6 months and 1 year in a subset of patients. Overall, 14.2% (n=3741) of patients were SHIFT type. These patients were more likely to be younger, men, have diabetes mellitus, ischemic heart disease, lower left ventricular ejection fraction, and more recent onset HF (<6 months; all,. From the Swedish Heart Failure Registry, 14.2% of patients with HF were eligible for ivabradine. These patients more commonly were not receiving target β-blocker dose. Over time, a minority of patients became ineligible and an even smaller minority became eligible.

Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Benzazepines; Cardiovascular Agents; Clinical Trials as Topic; Eligibility Determination; Female; Heart Failure, Systolic; Heart Rate; Humans; Ivabradine; Male; Middle Aged; Patient Selection; Registries; Stroke Volume; Sweden; Time Factors; Treatment Outcome; Ventricular Function, Left

Topics: Aged; Benzazepines; Cardiovascular Agents; Heart Failure; Heart Failure, Systolic; Heart Rate; Humans; Ivabradine; Treatment Outcome

Perhexiline, originally used as a first-line prophylactic antianginal agent, is now regarded primarily as a treatment for otherwise refractory myocardial ischemia. Recent studies have also demonstrated its short-term utility in heart failure, hypertrophic cardiomyopathy, and inoperable aortic stenosis. Its benefits on myocardial energetics state are potentially counter-balanced by risk of hepatotoxicity and peripheral neuropathy during long-term treatment if drug accumulation occurs. Since perhexiline exhibits complex pharmacokinetics with wide inter-individual variability, its long-term use requires regular plasma concentration monitoring. In this study, the risk of neuro- and hepato-toxicity during long-term perhexiline therapy in relation to the intensity of therapeutic drug monitoring was investigated. Furthermore, determinants of mortality during perhexiline treatment were evaluated.. In 170 patients treated with perhexiline for a median of 50 months (interquartile range: 31-94 months), outcomes and relationship to plasma drug concentrations were documented.. Rationale for treatment with perhexiline included myocardial ischemia in 88% and severe systolic heart failure in 38%. Plasma concentrations were within the therapeutic range of 150-600 ng/mL on 65% of assay occasions and toxic levels accounted for 8.8% of measurements. No patient developed hepatotoxicity attributable to perhexiline while 3 developed peripheral neuropathy possibly induced by treatment. Actuarial 5-year survival rate was 83% overall, and 76.3% in patients with associated systolic heart failure.. This first audit of a large population treated long-term perhexiline demonstrates the following: (1) Although the frequency of monitoring is less than ideal, therapeutic drug monitoring effectively limits occurrence of toxic drug concentrations and virtually eliminates long-term hepato- and neuro-toxicity and (2) Mortality rates during long-term therapy, notably for patients with concomitant heart failure, are surprisingly low.

Topics: Aged; Aged, 80 and over; Cardiovascular Agents; Drug Monitoring; Female; Follow-Up Studies; Heart Failure, Systolic; Humans; Male; Myocardial Ischemia; Perhexiline; Survival Rate; Time Factors

Topics: Cardiovascular Agents; Geriatrics; Heart Failure, Systolic; Humans; Hypotension, Orthostatic

Topics: Cardiovascular Agents; Geriatrics; Heart Failure, Systolic; Humans; Hypotension, Orthostatic

In heart failure, non-adherence increases events; in turn, the effect of hospitalization on adherence is incompletely understood. We explored the relationship of non-adherence to outcomes, hospitalizations with non-adherence, and the influence of non-adherence on treatment effects of heart rate lowering with ivabradine.. In the randomized, controlled Systolic Heart failure treatment with the If-inhibitor ivabradine Trial (SHIFT), we studied the effect of non-adherence (n = 1287) compared with adherence (n = 5204) on cardiovascular outcomes. After adjustment, non-adherence was associated with the primary composite endpoint of cardiovascular death and heart failure hospitalization (hazard ratio 3.47, 95% confidence interval 2.91-4.13, P < 0.0001). No interaction with the treatment groups of placebo or ivabradine (P for interaction 0.54) occurred. Similar results for cardiovascular death and heart failure hospitalization, as well as for cardiovascular hospitalization, heart failure death, and total death were observed. The effect of ivabradine was maintained in patients being adherent or becoming non-adherent during the trial (P for interaction = 0.54). Patients with a previous hospitalization were more likely to become non-adherent thereafter.. Non-adherence identifies a group at particularly high cardiovascular event risk independent of treatment allocation. Non-adherent patients in the ivabradine group maintain a treatment benefit. Patients with previous hospitalizations are more likely to become non-adherent and represent a group of particularly high-risk patients in whom special attention to stimulate adherence may be valuable.. ISRCTN70429960.

Topics: Aged; Benzazepines; Cardiovascular Agents; Cardiovascular Diseases; Cause of Death; Double-Blind Method; Female; Heart Failure; Heart Failure, Systolic; Hospitalization; Humans; Ivabradine; Male; Medication Adherence; Middle Aged; Mortality; Placebos; Proportional Hazards Models; Randomized Controlled Trials as Topic

Heart failure (HF) costs $21 billion annually in direct health care costs, 80% of which is directly attributable to hospitalizations. The SHIFT clinical study demonstrated that ivabradine plus standard of care (SoC) reduced HF-related and all-cause hospitalizations compared with SoC alone.. To estimate the budget impact of ivabradine from a U.S. commercial payer perspective.. A budget impact model estimated the per-member-per month (PMPM) impact of introducing ivabradine to existing formularies by comparing a reference scenario (SoC) and a new drug scenario (ivabradine + SoC) in hypothetical 1 million-member commercial and Medicare Advantage plans. In both scenarios, U.S. claims data were used for the reference cumulative annual rates of hospitalizations (HF, non-HF cardiovascular [CV], and non-CV), and hospitalization rates were adjusted using SHIFT data. The model controlled for mortality risk using SHIFT and U.S. life table data, and hospitalization costs were obtained from U.S. claims data: HF-related = $37,507; non-HF CV = $28,951; and non-CV = $17,904. The annualized wholesale acquisition cost of ivabradine was $4,500, with baseline use for this new drug at 2%, increasing 2% per year.. Based on the approved U.S. indication, approximately 2,000 commercially insured patients from a 1 million-member commercial plan were eligible to receive ivabradine. Ivabradine resulted in a PMPM cost savings of $0.01 and $0.04 in years 1 and 3 of the core model, respectively. After including the acquisition price for ivabradine, the model showed a decrease in total costs in the commercial ($991,256 and $474,499, respectively) and Medicare populations ($13,849,262 and $4,280,291, respectively) in year 1. This decrease was driven by ivabradine's reduction in hospitalization rates. For the core model, the estimated pharmacy-only PMPM in year 1 was $0.01 for the commercial population and $0.24 for the Medicare Advantage population.. Adding ivabradine to SoC led to lower average annual treatment costs. The negative PMPM budget impact indicates that ivabradine is an affordable option for U.S. payers.. This study was funded by Amgen. Patel is employed by Amgen; Kielhorn was employed by Amgen at the time of the study but is no longer affiliated with Amgen. Borer, Böhm, Ford, and Komajda have received scientific support, consultative fees, and/or speakers honoraria from Servier and Amgen in connection with SHIFT, the trial underlying this analysis. Borer also has received consultative fees from Celladon, Pfizer, ARMGO, Cardiorentis, Novartis, and Takeda USA. Kansal, Dorman, Krotneva, and Zheng are employees of Evidera, which was hired to assist with this study. Tavazzi has received research grants and consultation fees from Servier in connection with this study and has had advisory board memberships with Boston Scientific, Servier, Cardiorentis, Medtronic, St. Jude Medical, and CVie Therapeutics. Study concept and design were contributed by Dorman and Keilhorn, along with the other authors. Tavazzi, Komajda, Ford, BÖhm, and Borer oversaw collection of the data. Tavazzi, Komajda, Ford, BÖhm, and Borer (along with Karl Swedberg) formed the Executive Committee of SHIFT, the trial underlying this analysis. The manuscript was written by Kansal, along with the other authors, and revised by Borer and Patel, with assistance from the other authors.

Topics: Adult; Aged; Aged, 80 and over; Benzazepines; Budgets; Cardiovascular Agents; Drug Costs; Female; Heart Failure, Systolic; Humans; Insurance Claim Review; Insurance, Health; Ivabradine; Male; Medicare Part C; Middle Aged; Pharmacopoeias as Topic; Retrospective Studies; Standard of Care; United States; Young Adult

Topics: Aged; Cardiomyopathies; Cardiovascular Agents; Female; Heart Failure, Systolic; Humans; Male; Middle Aged; Mortality; Myocardial Ischemia; Retrospective Studies

B-type natriuretic peptide (BNP) and echocardiography are potentially useful adjunct to guide management of patients with chronic heart failure (HF).Thus, the aim of this retrospective, multicenter study was to compare outcomes and renal function in outpatients with chronic HF with reduced ejection fraction (HFrEF) who underwent an echo and BNP guided or a clinically driven protocol for follow-up.. In 1137 consecutive outpatients, management was guided according to echo-Doppler signs of elevated left ventricular filling pressure and BNP levels conforming to the protocol of the Network Labs Ultrasound (NEBULA) in HF Study Group in 570 (mean EF=30%), while management was clinically driven based on the institutional protocol of the HF Unit of the Cardiovascular and Thoracic Department in 567 (mean EF=33%). Propensity score, matching several confounding baseline variables, was used to match pairs based on treatment strategy. The median follow-up was 37.4months. After propensity matching, a lower incidence of death (HR 0.45, 95%CI: 0.30-0.67, p<0.0001), and death or worsening renal function (HR 0.49, 95%CI 0.36-0.67, p<0.0001) was apparent in echo-BNP-guided group compared to clinically-guided group. Worsening of renal function (≥0.3mg/dl increase in serum creatinine) was observed in 9.8% of echo-BNP-guided group and in 21.4% of clinical assessed group (p<0.0001). The daily dose of loop diuretics did not change in echo-BNP-guided group, while it increased in 65% of patients in clinically-guided group (p<0.0001).. Echo and BNP guided management may improve the outcome and reduce worsening of renal function in outpatients with chronic HFrEF.

Topics: Aged; Cardiovascular Agents; Diuretics; Drug Monitoring; Echocardiography, Doppler; Female; Heart Failure, Systolic; Humans; Italy; Kidney Function Tests; Male; Medication Therapy Management; Middle Aged; Natriuretic Peptide, Brain; Retrospective Studies; Treatment Outcome

Difficulties initiating and uptitrating β-blockers due to tolerability can complicate management of heart failure. Among other actions, β-blockers reduce heart rate, which is an important cardiovascular risk factor in heart failure. A new therapeutic strategy is ivabradine, which reduces resting heart rate and is associated with improved outcomes.. A 5-month, prospective, open-label, nonrandomized single-center study was performed in 69 patients. All patients had chronic heart failure with left ventricular systolic dysfunction in sinus rhythm, each were initiated on 3.125 mg twice daily (bid) carvedilol alone (n = 36) or 3.125 mg bid carvedilol/5 mg bid ivabradine (n = 33), on top of background therapy including angiotensin-converting enzyme inhibitor (88%), diuretics (86%), antiplatelet agents (91%), and statins (90%). Dosages were uptitrated every 2 weeks to 25 mg bid carvedilol in both groups and 7.5 mg bid ivabradine maximum in the carvedilol/ivabradine group. Uptitration of carvedilol lasted 1.9 ± 0.4 months with carvedilol/ivabradine and 2.8 ± 0.6 months with carvedilol alone (P < 0.05).. The patients receiving ivabradine had lower resting heart rate at 5 months (61.6 ± 3.1 versus 70.2 ± 4.4 bpm, P < 0.05). Adding ivabradine to carvedilol in patients with heart failure was associated with increases in the 6-min walk test and ejection fraction (all P < 0.05). Treatment tolerability was satisfactory. Patients receiving ivabradine and carvedilol had lower heart rates and better exercise capacity than those on carvedilol alone.. Adding ivabradine to carvedilol in patients with chronic heart failure improves the uptitration of β-blocker. The results merit further verification in a prospective double-blind study.

Topics: Adrenergic beta-Antagonists; Aged; Benzazepines; Carbazoles; Cardiovascular Agents; Carvedilol; Drug Therapy, Combination; Exercise; Exercise Tolerance; Female; Heart Failure, Systolic; Heart Rate; Humans; Ivabradine; Male; Middle Aged; Propanolamines; Prospective Studies; Risk Factors; Ventricular Dysfunction, Left

Analysis of 24-h Holter recordings was a pre-specified substudy of SHIFT (Systolic Heart Failure Treatment with the If Inhibitor Ivabradine Trial) for exploring the heart rhythm safety of ivabradine and to determine effects of ivabradine on 24-h, daytime, and night-time heart rate (HR) compared with resting office HR.. The 24-h Holter monitoring was performed at baseline and 8 months after randomization to ivabradine (n = 298) or matching placebo (n = 304) titrated maximally to 7.5 mg b.i.d. in patients with baseline HR ≥70 b.p.m. Patients received guideline-based optimized heart failure therapy including ACE inhibitors and/or ARBs in 93% and beta-blockers at maximally tolerated doses in 93%. After 8 months, HR over 24 h decreased by 9.5 ± 10.0 b.p.m. with ivabradine, from 75.4 ± 10.3 b.p.m. (P < 0.0001), and by 1.2 ± 8.9 b.p.m. with placebo, from 74.8 ± 9.7 b.p.m. (P < 0.0001 for difference vs. ivabradine). HR reduction with ivabradine was similar in resting office and in 24-h, awake, and asleep recordings, with beneficial effects on HR variability and no meaningful increases in supraventricular or ventricular arrhythmias. At 8 months, 21.3% on ivabradine vs. 8.5% on placebo had ≥1 episode of HR <40 b.p.m. (P < 0.0001). No episode of HR <30 b.p.m. was recorded; 3 (1.2%) patients had RR intervals >2.5 s on ivabradine vs. 4 (1.6%) patients on placebo. No RR intervals >3 s were identified in patients taking ivabradine.. Ivabradine safely and significantly lowers HR and improves HR variability in patients with systolic heart failure, without inducing significant bradycardia, ventricular arrhythmias, or supraventricular arrhythmias.

Topics: Aged; Benzazepines; Cardiovascular Agents; Electrocardiography, Ambulatory; Female; Heart Failure, Systolic; Heart Rate; Humans; Ivabradine; Male; Middle Aged; Prospective Studies

Patients with severe aortic stenosis (AS) and left ventricular systolic dysfunction pose a significant challenge to the managing physician. Conventional pharmacological therapy for systolic heart failure has not been proven beneficial in this setting. Ivabradine, a selective current inhibitor, decreases the spontaneous firing rate of sinoatrial nodal cells, thereby reducing the heart rate, and has been shown to reduce a composite end-point of heart failure hospitalization and mortality in patients with impaired left ventricular function. Herein are reported details of the hemodynamic effects and clinical outcome of ivabradine treatment in an 86-year-old man with severe AS and severe left ventricular systolic function.

Topics: Aged, 80 and over; Aortic Valve Stenosis; Benzazepines; Cardiac Catheterization; Cardiovascular Agents; Electrocardiography; Heart Failure, Systolic; Heart Rate; Heart Valve Prosthesis Implantation; Humans; Ivabradine; Male; Recovery of Function; Severity of Illness Index; Stroke Volume; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left

The aim of the study was to assess heart rate reduction for a acute decompensated heart failure in patients with reduced left ventricular systolic function and in patients with heart failure without significant reduction in ejection fraction. Were examined 79 patients with an ejection fraction less than 40%. 38 of them took If-channel blocker, ivabradine, 41 amounted to a control group. A group of patients with diastolic dysfunction was 48 patients (23 in the treatment of ivabradine and 25 subgroups of control). During the 14 days of observation it was found that the positive effect of reducing the sinus rate by ivabradine was observed in patients with diastolic dysfunction. In this group of patients on the background of decreasing heart rate, improves the passive diastolic properties of the left ventricle and an increase in the distance traveled by the patients during 6-minute walk test compared with the control group. The data obtained in our study support the use of ivabradine in patients with acute decompensated heart failure. The most significant changes in hemodynamic parameters and functional status were obtained in patients with diastolic dysfunction. Given the small sample, the results need to be further confirmed in larger clinical trials.

Topics: Acute Disease; Aged; Benzazepines; Cardiovascular Agents; Dose-Response Relationship, Drug; Drug Monitoring; Echocardiography; Exercise Test; Female; Heart Failure, Systolic; Heart Rate; Humans; Ivabradine; Male; Middle Aged; Statistics as Topic; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left

The prevalence, health care consumption, and mortality increase in elderly patients with heart failure. This study aimed to analyse long term cost expenditure and predictors of health care consumption in these patients.. We included 208 patients aged 60 years or older and hospitalised with heart failure (NYHA class II-IV and left ventricular systolic dysfunction); 58% were men, mean age 76 years, and mean ejection fraction 0.34. Data on all hospital admissions, discharge diagnoses, lengths of stay, and outpatient visits were collected from the National Board of Health and Welfare. We obtained data of all health care consumption for each individual.. After 8-12 years of prospective follow up 72% were dead (median survival 4.6 years). Main drivers of health care expenditure were non-cardiac (40%) and cardiac (29%) hospitalizations, and visits to primary care centres (16%), and hospital outpatient clinics (15%). On average, health care expenditures were € 36,447 per patient during follow up. The average yearly cost per patient was about 5,700€, in contrast to the estimated consumption of primary and hospital care in the general population: € 1,956 in 65-74 year olds and € 2,701 in 75-84 year olds. Poor quality of life (Nottingham Health Profile) was the strongest independent predictor of total health care consumption and costs (p<0.001; by multivariate analyses).. Health care costs in chronic systolic heart failure are at least two-fold higher than in the general population. Quality of life is a strong independent predictor of health care consumption.

Topics: Aged; Aged, 80 and over; Cardiovascular Agents; Chronic Disease; Female; Health Care Costs; Health Expenditures; Heart Failure, Systolic; Hospitalization; Humans; Long-Term Care; Male; Severity of Illness Index; Survival Analysis; Sweden

Topics: Adrenergic beta-Antagonists; Benzazepines; Cardiovascular Agents; Drug Administration Schedule; Drug Therapy, Combination; Heart Failure, Systolic; Heart Rate; Hospitalization; Humans; Ivabradine; Randomized Controlled Trials as Topic; Treatment Outcome

To determine the proportion of patients presenting with heart failure (HF) at Waikato Hospital who receive an evidence-based approach to care, and to investigate whether differences in guideline adherence between Maori and New Zealand Europeans (NZ Europeans) exist.. An audit of medical records was performed for a random sample of 71 Maori and 69 NZ European patients with a first admission for HF at the Waikato Hospital between 1/1/2007 and 31/8/2008. Information relating to investigation and management of HF was obtained from these records, with comparisons made between Maori and NZ Europeans.. Maori patients admitted with HF were significantly younger than NZ European with a mean age of 62 years compared to 78 years respectively (p<0.01). An echocardiogram was performed in 57% of cases. Angiotensin converting enzyme inhibitors and beta-blockers were prescribed to 96% and 82% of cases with systolic dysfunction and no contraindications respectively. Diuretics were prescribed to 84%, aldosterone antagonists to 17% and angiotensin receptor blockers to 4% of cases.. In this small retrospective series the adherence to key components of HF guidelines at Waikato Hospital is comparable with that seen in previous studies. Further studies with greater case numbers will be required to clarify whether there are differences in the investigation and treatment of HF between Maori and non-Maori.

Topics: Adrenergic beta-Antagonists; Adult; Age Factors; Aged; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Agents; Cross-Sectional Studies; Diuretics; Echocardiography; Evidence-Based Medicine; Female; Guideline Adherence; Healthcare Disparities; Heart Failure, Systolic; Hospitalization; Humans; Male; Medical Audit; Middle Aged; Mineralocorticoid Receptor Antagonists; New Zealand; Population Groups; Retrospective Studies; White People

Topics: Cardiovascular Agents; Evidence-Based Medicine; Heart Failure, Systolic; Humans; Phosphodiesterase 5 Inhibitors; Treatment Outcome

Topics: Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Agents; Drug Combinations; Evidence-Based Medicine; Heart Failure, Systolic; Hemodynamics; Humans; Hydralazine; Isosorbide Dinitrate; Randomized Controlled Trials as Topic; Renal Insufficiency; Treatment Outcome

Cystatin C, which has long been regarded as a biomarker that indicates kidney functions, has recently been recognized as an inflammatory marker in the human body.. To elucidate how cystatin C is related to the prognosis of systolic heart failure patients.. Patients with systolic heart failure who were admitted to the fourth affiliated hospital of Harbin Medical University between January and April 2008 were enrolled in this study. Serum homocysteine, high-sensitivity C-reactive protein (hs-CRP) and cystatin C levels were determined and all the patients received an average of 2 years of follow-up for occurrence of death, heart transplantation or readmission with worsening heart failure.. Of 138 patients enrolled, those who experienced adverse outcomes (e.g. cardiac death, heart transplantation or progressive heart failure) (n = 21) had considerably higher mean levels of serum homocysteine (28.6 ± 13.4 vs 14.4 ± 6.3mg/L; P < 0.01), hs-CRP (17.5 ± 14.1 vs 6.4 ± 7.7 μmol/L; p < 0.01) and cystatin C (1.63 ± 0.81 vs 0.91 ± 0.27 mg/L; P < 0.01) than those without adverse outcomes (n = 117). Furthermore, the Cox proportional hazards model demonstrated that serum homocysteine, hs-CRP and cystatin C are all independent predictors of adverse outcomes.. Cystatin C, together with hs-CRP and homocysteine, is an independent risk factor that is important in the prognosis of patients with systolic heart failure.

Topics: Aged; Biomarkers; C-Reactive Protein; Cardiovascular Agents; China; Cystatin C; Disease Progression; Female; Heart Failure, Systolic; Heart Transplantation; Homocysteine; Hospitals, University; Humans; Inflammation Mediators; Kaplan-Meier Estimate; Male; Middle Aged; Proportional Hazards Models; Prospective Studies; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Up-Regulation

Topics: Aged; Benzazepines; Cardiovascular Agents; Female; Heart Failure, Systolic; Heart Rate; Hospitalization; Humans; Ivabradine; Male; Middle Aged; Randomized Controlled Trials as Topic; Stroke Volume; Treatment Outcome

Topics: Benzazepines; Cardiovascular Agents; Clinical Trials as Topic; Cyclic Nucleotide-Gated Cation Channels; Drug Therapy, Combination; Germany; Heart Failure, Systolic; Heart Rate; Humans; Ivabradine; Multicenter Studies as Topic; Patient Admission; Survival Rate

Brain natriuretic peptide (BNP) and N-Terminal pro natriuretic peptide (NT-proBNP) are widely accepted to diagnose congestive heart failure (CHF) in the emergency room. The aim of this study was to evaluate the value of BNP and NT-proBNP to diagnose CHF in primary care.. Clinical and Doppler-echocardiographic assessment of patients referred by their general practitioner (GP) with the diagnosis of CHF. Receiver operating curves were used to evaluate the accuracy of BNP and NT-proBNP for echocardiographically confirmed systolic and/or diastolic heart failure.. Three hundred and eighty four patients (mean age of 65) were included. One hundred and ninety three (50%) patients had systolic heart failure and 31 (8%) had isolated diastolic heart failure. Using currently recommended cut-off values of BNP (less than 100 pg/ml) and NT-proBNP (less than 125 pg/ml) for exclusion of CHF, BNP was false negative in 25% and NT-proBNP in 10% of the patients. The area under the curve was better for NT-proBNP than for BNP (0.742 vs. 0.691).. In this population with a high prevalence of CHF, BNP and NT-proBNP failed to adequately rule out CHF. GP's should be cautious when using BNP and NT-proBNP in primary care. An echocardiography remains compulsory in unexplained dyspnea.

Topics: Aged; Biomarkers; Cardiovascular Agents; Chronic Disease; Dyspnea; Echocardiography, Doppler; Female; Heart Failure, Diastolic; Heart Failure, Systolic; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Primary Health Care; Prospective Studies; Referral and Consultation; ROC Curve; Switzerland; Treatment Outcome

Corin, a transmembrane serine protease expressed in cardiomyocytes, cleaves pro-atrial natriuretic peptide and pro-brain natriuretic peptide (BNP) into biologically active peptide hormones. The minor corin I555(P568) allele, defined by the T555I and Q568P mutations, is common in persons of African ancestry and associated with increased risk for hypertension and cardiac concentric hypertrophy. The corin gene product containing the T555I and Q568P mutations has significantly reduced natriuretic peptide processing capacity. We hypothesized that the corin I555(P568) allele would be associated with adverse outcomes and impaired BNP processing in blacks with systolic heart failure.. This is a retrospective study of 354 subjects in the African American Heart Failure Trial Genetic Risk Assessment in Heart Failure substudy. In the corin variant group (n=50) compared with corin nonvariant group (n=300), BNP-32 (amino acids 77 to 108) was lower (190 pg/mL versus 340 pg/mL, P=0.007), but the ratio of unprocessed BNP(1 to 108)/processed BNP-32 was significantly higher (P=0.05). Stratified analyses were conducted because of evidence of significant interaction between the corin I555(P568) allele and treatment assignment. In the placebo arm, multivariable analysis demonstrated that the corin I555(P568) allele was associated with increased risk for death or heart failure hospitalization (relative risk 3.49; 95% CI, 1.45 to 8.39; P=0.005); however, in the treatment arm (fixed-dose combination isosorbide-dinitrate/hydralazine), the corin I555(P568) allele was not associated with adverse outcomes.. We have identified a pharmacogenomic interaction in blacks with systolic heart failure. The corin I555(P568) allele is associated with an increased risk for death or heart failure hospitalization in patients receiving standard neurohormonal blockade, but the addition of fixed-dose combination isosorbide-dinitrate/hydralazine ameliorates this risk. A plausible mechanism for this pharmacogenomic interaction is the impaired processing of BNP in carriers of the corin I555(P568) allele as compared with noncarriers.

Topics: Black or African American; Cardiovascular Agents; Double-Blind Method; Drug Combinations; Female; Gene Frequency; Genetic Predisposition to Disease; Heart Failure, Systolic; Hospitalization; Humans; Hydralazine; Immunoassay; Isosorbide Dinitrate; Kaplan-Meier Estimate; Male; Middle Aged; Multicenter Studies as Topic; Mutation; Natriuretic Peptide, Brain; Phenotype; Proportional Hazards Models; Protein Processing, Post-Translational; Randomized Controlled Trials as Topic; Retrospective Studies; Risk Assessment; Risk Factors; Serine Endopeptidases; Treatment Outcome; United States