Six-minute walk test: prognostic value and effects of nebivolol versus placebo in elderly patients with heart failure from the SENIORS trial.

BACKGROUND: There is limited information about the 6-min walk test (6MWT) in elderly patients with heart failure. We evaluated 6MWT and the effect of nebivolol on 6MWT from the SENIORS trial. METHODS AND RESULTS: The SENIORS trial evaluated nebivolol versus placebo on death and hospitalisation in patients aged ≥ 70 years with heart failure. A total of 1982 patients undertook a 6MWT at baseline and 1716 patients at 6 months. Patients were divided into tertiles (≤ 200 m, 201 to ≤ 300 m and > 300 m) and to change in distance walked between baseline and 6 months (< 0 m, 0 to < 30 m and ≥ 30 m). The primary outcome was all-cause mortality and cardiovascular hospital admission. Secondary endpoint was all-cause mortality. Baseline walk distance of ≤ 200 m incurred a greater risk of the primary and secondary outcomes (HR 1.41, CI 95% 1.17-1.69, p < 0.001) and (HR 1.37, CI 95% 1.05-1.78, p = 0.019). A decline in walk distance over 6 months was associated with increased risk of clinical events. Nebivolol had no influence on change in walk distance over 6 months. CONCLUSIONS: The 6MWT has prognostic utility in elderly patients. Those who walked less than 200 m were at highest risk. Nebivolol had no effect on 6MWT.

A Randomized Trial of Video-based Education in Patients With Heart Failure: The Congestive Heart Failure Outreach Program of Education (COPE).

BACKGROUND: Heart failure (HF) exacerbations often relate to poor self-care. Education programs improve outcomes, but are resource-intensive. We developed a video-based educational intervention and evaluated it in patients with HF. METHODS: Congestive Heart Failure Outreach Program of Education was a pragmatic multicenter randomized trial. We included subjects with HF if they were hospitalized, seen in the emergency department (ED), or high-risk outpatients, and randomized them to intervention or control. Intervention included a 20-minute video, supplementary booklet, and 3 bimonthly newsletters focusing on salt and fluid restriction, daily weights, and medications. Subjects watched the video and were encouraged to review it at home, along with the booklet/newsletters. Control subjects received the booklet only. The primary outcome was the difference in cardiovascular hospitalizations or ED visits between groups at 6 months. Secondary outcomes included clinical events and in-hospital days. RESULTS: We recruited 539 subjects from 22 centers in Canada and the United States. Baseline characteristics were similar in both groups: 64% were male and had a mean age of 66 (± 13) years, mean ejection fraction 31% (± 13.5), and 65% New York Heart Association Functional Classification III/IV. The primary outcome occurred in 57 subjects (21%) in the intervention group compared with 61 subjects (23%) in the control group (P = 0.66). There were no significant differences in prespecified secondary outcomes; however, death occurred in 18 subjects (7%) in the intervention group and 33 subjects (12%) in the control group (P = 0.03). CONCLUSION: Video education on self-care did not reduce hospitalizations or ED visits in patients with HF. Of note, mortality was lower in the intervention group.

INTRODUCTION: L'exacerbation de l'insuffisance cardiaque (IC) est souvent liée à une mauvaise prise en charge autonome des soins. Les programmes d'enseignement améliorent les résultats cliniques, mais exigent beaucoup de ressources. Nous avons conçu une intervention éducative par vidéo et l'avons évaluée auprès de patients atteints d'IC. MÉTHODES: Le Congestive Heart Failure Outreach Program of Education était une étude pragmatique multicentrique à répartition aléatoire. Nous avons sélectionné les sujets atteints d'IC s'ils étaient hospitalisés, vus au service des urgences (SU) ou patients en consultation externe exposés à un risque élevé, et les avons répartis de manière aléatoire au groupe d'intervention ou au groupe témoin. L'intervention a consisté en une vidéo de 20 minutes, un livret supplémentaire et 3 bulletins bimensuels portant sur la restriction du sel et des liquides, les mesures quotidiennes du poids et les médicaments. Après que les sujets eurent regardé la vidéo, nous les avons encouragés à la revoir à la maison, en plus de lire le livret et les bulletins. Les sujets témoins ont reçu seulement le livret. Le critère de jugement principal était la différence dans les hospitalisations en raison d'une maladie cardiovasculaire ou les visites au SU entre les groupes après 6 mois. Les critères de jugement secondaires étaient les événements cliniques et les jours d'hospitalisation. RÉSULTATS: Nous avons recruté 539 sujets de 22 centres au Canada et aux États-Unis. Les caractéristiques initiales étaient similaires dans les 2 groupes : 64 % étaient des hommes et avaient un âge moyen de 66 ans (± 13), une fraction d'éjection moyenne de 31 % (± 13,5), et 65 % avaient une classification fonctionnelle III/IV de la New York Heart Association. Le critère de jugement principal est survenu chez 57 sujets (21 %) dans le groupe d'intervention et chez 61 sujets (23 %) dans le groupe témoin (P = 0,66). Il n'y a eu aucune différence significative dans les critères secondaires prédéfinis. Toutefois, 18 sujets (7 %) du groupe d'intervention et 33 sujets (12 %) du groupe témoin sont morts (P = 0,03). CONCLUSION: L'enseignement sur les autosoins par vidéo n'a pas réduit les hospitalisations ou les visites au SU des patients atteints d'IC. Notamment, la mortalité a été plus faible dans le groupe d'intervention.

Effect of age and sex on efficacy and tolerability of ß blockers in patients with heart failure with reduced ejection fraction: individual patient data meta-analysis.

OBJECTIVES: To determine the efficacy and tolerability of ß blockers in a broad age range of women and men with heart failure with reduced ejection fraction (HFrEF) by pooling individual patient data from placebo controlled randomised trials. DESIGN: Prospectively designed meta-analysis of individual patient data from patients aged 40-85 in sinus rhythm at baseline, with left ventricular ejection fraction <0.45. PARTICIPANTS: 13,833 patients from 11 trials; median age 64; 24% women. MAIN OUTCOME MEASURES: The primary outcome was all cause mortality; the major secondary outcome was admission to hospital for heart failure. Analysis was by intention to treat with an adjusted one stage Cox proportional hazards model. RESULTS: Compared with placebo, ß blockers were effective in reducing mortality across all ages: hazard ratios were 0.66 (95% confidence interval 0.53 to 0.83) for the first quarter of age distribution (median age 50); 0.71 (0.58 to 0.87) for the second quarter (median age 60); 0.65 (0.53 to 0.78) for the third quarter (median age 68); and 0.77 (0.64 to 0.92) for the fourth quarter (median age 75). There was no significant interaction when age was modelled continuously (P=0.1), and the absolute reduction in mortality was 4.3% over a median follow-up of 1.3 years (number needed to treat 23). Admission to hospital for heart failure was significantly reduced by ß blockers, although this effect was attenuated at older ages (interaction P=0.05). There was no evidence of an interaction between treatment effect and sex in any age group. Drug discontinuation was similar regardless of treatment allocation, age, or sex (14.4% in those give ß blockers, 15.6% in those receiving placebo). CONCLUSION: Irrespective of age or sex, patients with HFrEF in sinus rhythm should receive ß blockers to reduce the risk of death and admission to hospital.Registration PROSPERO CRD42014010012; Clinicaltrials.gov NCT00832442.

Efficacy of ß blockers in patients with heart failure plus atrial fibrillation: an individual-patient data meta-analysis.

BACKGROUND: Atrial fibrillation and heart failure often coexist, causing substantial cardiovascular morbidity and mortality. ß blockers are indicated in patients with symptomatic heart failure with reduced ejection fraction; however, the efficacy of these drugs in patients with concomitant atrial fibrillation is uncertain. We therefore meta-analysed individual-patient data to assess the efficacy of ß blockers in patients with heart failure and sinus rhythm compared with atrial fibrillation. METHODS: We extracted individual-patient data from ten randomised controlled trials of the comparison of ß blockers versus placebo in heart failure. The presence of sinus rhythm or atrial fibrillation was ascertained from the baseline electrocardiograph. The primary outcome was all-cause mortality. Analysis was by intention to treat. Outcome data were meta-analysed with an adjusted Cox proportional hazards regression. The study is registered with Clinicaltrials.gov, number NCT0083244, and PROSPERO, number CRD42014010012. FINDINGS: 18,254 patients were assessed, and of these 13,946 (76%) had sinus rhythm and 3066 (17%) had atrial fibrillation at baseline. Crude death rates over a mean follow-up of 1·5 years (SD 1·1) were 16% (2237 of 13,945) in patients with sinus rhythm and 21% (633 of 3064) in patients with atrial fibrillation. ß-blocker therapy led to a significant reduction in all-cause mortality in patients with sinus rhythm (hazard ratio 0·73, 0·67-0·80; p<0·001), but not in patients with atrial fibrillation (0·97, 0·83-1·14; p=0·73), with a significant p value for interaction of baseline rhythm (p=0·002). The lack of efficacy for the primary outcome was noted in all subgroups of atrial fibrillation, including age, sex, left ventricular ejection fraction, New York Heart Association class, heart rate, and baseline medical therapy. INTERPRETATION: Based on our findings, ß blockers should not be used preferentially over other rate-control medications and not regarded as standard therapy to improve prognosis in patients with concomitant heart failure and atrial fibrillation. FUNDING: Menarini Farmaceutica Internazionale (administrative support grant).

Do calcium channel blockers increase the diagnosis of heart failure in patients with hypertension?

Calcium channel blockers (CCBs) are widely used to control hypertension. Previous work suggested that their use could increase heart failure (HF), which is 1 of the consequences of uncontrolled hypertension. Information about the effect of CCBs on incident HF in patients with hypertension is scarce. A systematic review was conducted to evaluate patients with hypertension treated with CCBs and incident HF. An electronic search of publications was conducted using 8 major databases. Studies were eligible if they (1) were randomized clinical trials, (2) performed comparisons of CCBs versus active control, (3) randomized >200 patients, (4) had follow-up periods >6 months, and (5) provided data regarding incident HF. Trials of renal transplantation patients, placebo-controlled trials, and HF trials were excluded. A total of 156,766 patients were randomized to CCBs or control, with a total of 5,049 events. The analysis indicated a significant increase in the diagnosis of HF in patients allocated to CCBs (odds ratio 1.18, 95% confidence interval 1.07 to 1.31). The effect observed was independent of incident myocardial infarction. Subgroup analyses indicated that patients with diabetes were at higher risk for developing HF (odds ratio 1.71, 95% confidence interval 1.21 to 2.41). In conclusion, the results suggest that patients with hypertension treated with CCBs have increased incident HF.

Metformin treatment in diabetes and heart failure: when academic equipoise meets clinical reality.

OBJECTIVE: Metformin has had a 'black box' contraindication in diabetic patients with heart failure (HF), but many believe it to be the treatment of choice in this setting. Therefore, we attempted to conduct a pilot study to evaluate the feasibility of undertaking a large randomized controlled trial with clinical endpoints. STUDY DESIGN: The pilot study was a randomized double blinded placebo controlled trial. Patients with HF and type 2 diabetes were screened in hospitals and HF clinics in Edmonton, Alberta, Canada (population ~1 million). Major exclusion criteria included the current use of insulin or high dose metformin, decreased renal function, or a glycosylated hemoglobin <7%. Patients were to be randomized to 1500 mg of metformin daily or matching placebo and followed for 6 months for a variety of functional outcomes, as well as clinical events. RESULTS: Fifty-eight patients were screened over a six month period and all were excluded. Because of futility with respect to enrollment, the pilot study was abandoned. The mean age of screened patients was 77 (SD 9) years and 57% were male. The main reasons for exclusion were: use of insulin therapy (n = 23; 40%), glycosylated hemoglobin <7% (n = 17; 29%) and current use of high dose metformin (n = 12; 21%). Overall, contraindicated metformin therapy was the most commonly prescribed oral antihyperglycemic agent (n = 27; 51%). On average, patients were receiving 1,706 mg (SD 488 mg) of metformin daily and 12 (44%) used only metformin. CONCLUSION: Despite uncertainty in the scientific literature, there does not appear to be clinical uncertainty with regards to the safety or effectiveness of metformin in HF making a definitive randomized trial virtually impossible. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00325910.

Effect of fish oil on arrhythmias and mortality: systematic review.

OBJECTIVE: To synthesise the literature on the effects of fish oil-docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA)-on mortality and arrhythmias and to explore dose response and formulation effects. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Medline, Embase, the Cochrane Library, PubMed, CINAHL, IPA, Web of Science, Scopus, Pascal, Allied and Complementary Medicine, Academic OneFile, ProQuest Dissertations and Theses, Evidence-Based Complementary Medicine, and LILACS. Studies reviewed Randomised controlled trials of fish oil as dietary supplements in humans. DATA EXTRACTION: The primary outcomes of interest were the arrhythmic end points of appropriate implantable cardiac defibrillator intervention and sudden cardiac death. The secondary outcomes were all cause mortality and death from cardiac causes. Subgroup analyses included the effect of formulations of EPA and DHA on death from cardiac causes and effects of fish oil in patients with coronary artery disease or myocardial infarction. DATA SYNTHESIS: 12 studies totalling 32 779 patients met the inclusion criteria. A neutral effect was reported in three studies (n=1148) for appropriate implantable cardiac defibrillator intervention (odds ratio 0.90, 95% confidence interval 0.55 to 1.46) and in six studies (n=31 111) for sudden cardiac death (0.81, 0.52 to 1.25). 11 studies (n=32 439 and n=32 519) provided data on the effects of fish oil on all cause mortality (0.92, 0.82 to 1.03) and a reduction in deaths from cardiac causes (0.80, 0.69 to 0.92). The dose-response relation for DHA and EPA on reduction in deaths from cardiac causes was not significant. CONCLUSIONS: Fish oil supplementation was associated with a significant reduction in deaths from cardiac causes but had no effect on arrhythmias or all cause mortality. Evidence to recommend an optimal formulation of EPA or DHA to reduce these outcomes is insufficient. Fish oils are a heterogeneous product, and the optimal formulations for DHA and EPA remain unclear.

Economic implications of treatment guidelines for congestive heart failure.

Congestive heart failure (CHF) is the most common cause of cardiovascular hospital admission. A significant proportion of the costs of CHF is due to hospitalizations. The present study evaluated the economic impact of a modest increase in the use of angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, spironolactone and digoxin on CHF hospitalizations. Patients with CHF were identified through the Canadian Institute for Health Information (CIHI) database. The efficacy of ACE inhibitors, beta-blockers, spironolactone and digoxin in the first year of treatment were retrieved from the Survival and Ventricular Enlargement (SAVE) trial, a meta-analysis, the Randomized Aldactone Evaluation Study (RALES) and the Digitalis Investigation Group (DIG) trial, respectively. Cost of CHF hospitalization was based on the National List of Provincial Costs. Costs of drug treatment were based on the 2002 Alberta Health and Wellness Drug Benefit list. Physician visits for drug titration were also included in the model. A total of 85,679 patients with CHF were identified with a total of 106,130 hospital discharges. A 10% increase in use of ACE inhibitors, beta-blockers, spironolactone and digoxin would incur in a total cost due to avoidable hospital admissions of 0.4 million dollars, 1.3 million dollars, 3.7 million dollars and 1.2 million dollars, respectively. Similarly, the costs of drug treatment would be 2.2 million dollars, 1.3 million dollars, 0.3 million dollars and 0.5 million dollars, respectively. An increase in the use of the above medications would save 6.6 million dollars due to avoidable hospital admissions. The total cost of drug treatment was 4.3 million dollars, giving a net savings of 2.3 million dollars in the first year. The implementation of evidence-based therapy for CHF treatment is not only clinically efficacious, but also economically attractive.

Utilization of evidence-based therapies for heart failure in the institutionalized elderly.

OBJECTIVES: Heart failure (HF) is a major source of morbidity and mortality in elderly populations. A significant proportion of the elderly with HF are living in long-term care facilities. Little is known about their management. The aim of this study was to evaluate the use of evidence-based therapies in institutionalized elderly patients with HF. DESIGN, SETTING AND PARTICIPANTS: Retrospective chart review conducted at 15 long-term care facilities in the Capital Health Region (Edmonton, Alberta). Residents > or =65 years of age with HF were identified using a pharmacy database. RESULTS: Overall prevalence of HF was 15% (313/2062 residents). Mean age was 87 years, median duration of residence was 1.8 years. Utilization of ACE-inhibitors, beta-blockers and spironolactone was 51%, 16% and 10%, respectively. Use of these medications was not significantly different between subgroups of those with and without contraindications to the therapies, different advance directive levels, gender or age. Sodium and fluid restricted diets were prescribed in only 11.0% and 3.8% of residents. Weight was not regularly monitored. Influenza and pneumococcal vaccination were administered to 60.4% and 81.2% of the residents. CONCLUSION: The use of evidence-based therapies in institutionalized elderly patients with HF is low, and unexplained by contraindications or advance directives. Efforts to increase the utilization of evidence-based therapies and improve monitoring are warranted.

Randomized trial to determine the effect of nebivolol on mortality and cardiovascular hospital admission in elderly patients with heart failure (SENIORS).

AIMS: Large randomized trials have shown that beta-blockers reduce mortality and hospital admissions in patients with heart failure. The effects of beta-blockers in elderly patients with a broad range of left ventricular ejection fraction are uncertain. The SENIORS study was performed to assess effects of the beta-blocker, nebivolol, in patients >/=70 years, regardless of ejection fraction. METHODS AND RESULTS: We randomly assigned 2128 patients aged >/=70 years with a history of heart failure (hospital admission for heart failure within the previous year or known ejection fraction 35%), and 68% had a prior history of coronary heart disease. The mean maintenance dose of nebivolol was 7.7 mg and of placebo 8.5 mg. The primary outcome occurred in 332 patients (31.1%) on nebivolol compared with 375 (35.3%) on placebo [hazard ratio (HR) 0.86, 95% CI 0.74-0.99; P=0.039]. There was no significant influence of age, gender, or ejection fraction on the effect of nebivolol on the primary outcome. Death (all causes) occurred in 169 (15.8%) on nebivolol and 192 (18.1%) on placebo (HR 0.88, 95% CI 0.71-1.08; P=0.21). CONCLUSION: Nebivolol, a beta-blocker with vasodilating properties, is an effective and well-tolerated treatment for heart failure in the elderly.

Contemporary burden of illness of congestive heart failure in Canada.

BACKGROUND: Congestive heart failure (CHF) is associated with high morbidity and mortality; however, there is little contemporary Canadian data to quantify the burden of this illness. OBJECTIVE: To report the impact of CHF in Canada, as measured by hospitalizations. METHODS: Data were obtained from the Canadian Institute for Health Information on patients hospitalized with CHF as a most responsible, primary or complication diagnosis during fiscal year 2000/01. RESULTS: There were a total of 106,130 discharges for 85,679 CHF patients in the fiscal year 2000/01. Total in-hospital mortality was 15.8%. In terms of total discharges for CHF, 32.7% were readmissions. On an individual patient basis, 19.9% of patients were rehospitalized once or more during 2000. In terms of burden of illness of CHF compared with other major illnesses, CHF is associated with the second highest total number of hospital days and third highest number of patients affected. CONCLUSIONS: Hospitalization for CHF occurs frequently and accounts for a large number of hospital bed-days in Canada. These figures should signal a call to action for researchers, administrators and health care providers regarding the need for more efficacious therapies, better application of already-proven therapies and patient education.

Systematic Review of Hirudin in Acute Coronary Syndromes and Percutaneous Coronary Intervention.

Thrombin plays a key role in the pathogenesis of acute coronary syndromes because it is a potent platelet agonist and converts fibrinogen to fibrin. Hirudin is a powerful, direct, and specific antithrombin agent that can be used in many therapeutic scenarios in which heparin is routinely used. In this systemic review, we summarize evidence from randomized clinical trials evaluating the benefits and risks of recombinant hirudin for the treatment of acute coronary syndromes and patients undergoing percutaneous coronary intervention.