Cost-effectiveness of eplerenone in patients with systolic heart failure and mild symptoms

Aim In the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF), aldosterone blockade with eplerenone decreased mortality and hospitalisation in patients with mild symptoms (New York Heart Association class II) and chronic systolic heart failure (HF). The present study evaluated the cost-effectiveness of eplerenone in the treatment of these patients in the UK and Spain.<p></p> Methods and results Results from the EMPHASIS-HF trial were used to develop a discrete-event simulation model estimating lifetime direct costs and effects (life years and quality-adjusted life years (QALYs) gained) of the addition of eplerenone to standard care among patients with chronic systolic HF and mild symptoms. Eplerenone plus standard care compared with standard care alone increased lifetime direct costs per patient by £4284 for the UK and €7358 for Spain, with additional quality-adjusted life expectancy of 1.22 QALYs for the UK and 1.33 QALYs for Spain. Mean lifetime costs were £3520 per QALY in the UK and €5532 per QALY in Spain. Probabilistic sensitivity analysis suggested a 100% likelihood of eplerenone being regarded as cost-effective at a willingness-to-pay threshold of £20 000 per QALY (UK) or €30 000 per QALY (Spain).<p></p> Conclusions By currently accepted standards of value for money, the addition of eplerenone to optimal medical therapy for patients with chronic systolic HF and mild symptoms is likely to be cost-effective.<p></p&gt

Nebulized Furosemide for the Management of Dyspnea: Does the Evidence Support Its Use?

Dyspnea is a common and distressing symptom associated with multiple chronic illness and high levels of burden for individuals, their families and health care systems. The subjective nature dyspnea and a poor understanding of pathophysiological mechanisms challenge the clinician in developing management plans. Nebulized furosemide has been identified as a novel approach to dyspnea management. This review summarizes published studies, both clinical and experimental, reporting the use of nebulized furosemide. The search criteria yielded 42 articles published in the period 1988 to 2004. Although nebulized furosemide appeared to have a positive influence on dyspnea and physiological measurements, caution must be taken with the results primarily coming from small-scale clinical trials or observation trials. Despite the limitations of the studies reported, given the range of conditions reporting effectiveness of nebulized furosemide, further investigation of this potential novel treatment of dyspnea is warranted

Predictors of normotension on withdrawal of antihypertensive drugs in elderly patients: prospective study in second Australian national blood pressure study cohort

Objectives: To identify simple long term predictors of maintenance of normotension after withdrawal of antihypertensive drugs in elderly patients in general practice. Design: Prospective cohort study. Setting: 169 general practices in Victoria, Australia. Participants: 503 patients aged 65-84 with treated hypertension who were withdrawn from all antihypertensive drugs and remained drug free and normotensive for an initial two week period; all were followed for a further 12 months. Main outcome measures: Relative likelihood of maintaining normotension 12 months after drug withdrawal; relative likelihood of early return to hypertension after drug withdrawal. Results: The likelihood of remaining normotensive at 12 months was greater among younger patients (65-74 years), patients with lower "on-treatment" systolic blood pressure, patients on single agent treatment, and patients with a greater waist:hip ratio. The likelihood of return to hypertension was greatest for patients with higher "on-treatment" systolic blood pressure. Conclusions: Age, blood pressure control, and the number of antihypertensive drugs are important factors in the clinical decision to withdraw drug treatment. Because of consistent rates of return to antihypertensive treatment, all patients from whom such treatment is withdrawn should be monitored indefinitely to detect a recurrence of hypertension.Mark R Nelson, Chris M Reid, Henry Krum, Tui Muir, Philip Ryan, John J McNei

353 Eplerenone benefit at 30 days in high‐risk subgroups in the EPHESUS trial

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106771/1/ehfs80218-8.pd

3',4'-Dihydroxyflavonol antioxidant attenuates aiastolic dysfunction and cardiac remodeling in streptozotocin-induced diabetic m(Ren2)27 rats

Background Diabetic cardiomyopathy (DCM) is an increasingly recognized cause of chronic heart failure amongst diabetic patients. Both increased reactive oxygen species (ROS) generation and impaired ROS scavenging have been implicated in the pathogenesis of hyperglycemia-induced left ventricular dysfunction, cardiac fibrosis, apoptosis and hypertrophy. We hypothesized that 3',4'-dihydroxyflavonol (DiOHF), a small highly lipid soluble synthetic flavonol, may prevent DCM by scavenging ROS, thus preventing ROS-induced cardiac damage. Methodology/Principal Findings Six week old homozygous Ren-2 rats were randomized to receive either streptozotocin or citrate buffer, then further randomized to receive either DiOHF (1 mg/kg/day) by oral gavage or vehicle for six weeks. Cardiac function was assessed via echocardiography and left ventricular cardiac catheterization before the animals were sacrificed and hearts removed for histological and molecular analyses. Diabetic Ren-2 rats showed evidence of diastolic dysfunction with prolonged deceleration time, reduced E/A ratio, and increased slope of end-diastolic pressure volume relationship (EDPVR) in association with marked interstitial fibrosis and oxidative stress (all P<0.05 vs control Ren-2). Treatment with DiOHF prevented the development of diastolic dysfunction and was associated with reduced oxidative stress and interstitial fibrosis (all P<0.05 vs untreated diabetic Ren-2 rats). In contrast, few changes were seen in non-diabetic treated animals compared to untreated counterparts. Conclusions Inhibition of ROS production and action by DiOHF improved diastolic function and reduced myocyte hypertrophy as well as collagen deposition. These findings suggest the potential clinical utility of antioxidative compounds such as flavonols in the prevention of diabetes-associated cardiac dysfunction

Acute heart failure admissions in New South Wales and the Australian Capital Territory: the NSW HF Snapshot Study

Objective: The primary aim of the NSW Heart Failure (HF) Snapshot was to obtain a representative cross-sectional view of patients with acute HF and their management in New South Wales and Australian Capital Territory hospitals. Design and setting: A prospective audit of consecutive patients admitted to 24 participating hospitals in NSW and the ACT with a diagnosis of acute HF was conducted from 8 July 2013 to 8 August 2013. Results: A total of 811 participants were recruited (mean age, 77 ± 13 years; 58% were men; 42% had a left ventricular ejection fraction ≥ 50%). The median Charlson Comorbidity Index score was 3, with ischaemic heart disease (56%), renal disease (55%), diabetes (38%) and chronic lung disease (32%) the most frequent comorbidities; 71% of patients were assessed as frail. Intercurrent infection (22%), non-adherence to prescribed medication (5%) or to dietary or fluid restrictions (16%), and atrial fibrillation/flutter (15%) were the most commonly identified precipitants of HF. Initial treatment included intravenous diuretics (81%), oxygen therapy (87%), and bimodal positive airways pressure or continuous positive airways pressure ventilation (17%). During the index admission, 6% of patients died. The median length of stay in hospital was 6 days, but ranged between 3 and 12 days at different hospitals. Just over half the patients (59%) were referred to a multidisciplinary HF service. Discharge medications included angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (59%), β-blockers (66%) and loop diuretics (88%).Conclusions: Patients admitted to hospital with acute HF in NSW and the ACT were generally elderly and frail, with multiple comorbidities. Evidence-based therapies were underused, and there was substantial interhospital variation in the length of stay. We anticipate that the results of the HF Snapshot will inform the development of strategies for improving the uptake of evidence-based therapies, and hence outcomes, for HF patients

How Do Brazilian Street Youth Experience ‘The Street’?: Analysis Of A Sentence Completion Task

This study investigated how homeless Brazilian youth experience the street and examined factors linked to positive and negative feelings about the street. An opportunity sample of 35 boys and 34 girls aged 10–18 completed a structured interview and sentence completion task aimed at eliciting open-ended responses in a standardized manner. Analyses revealed great diversity in youths’ views of the street; moreover, in analyses controlling for age and gender, youth reporting feeling positive on the street differed from those who felt negative in reasons for leaving home, family situation and daily survival. The findings support the value of the sentence completion task in exploring the subjective experiences of street youth

Age-specific diastolic dysfunction improves prediction of symptomatic heart failure by Stage B heart failure

Aims: We investigated whether addition of diastolic dysfunction (DD) and longitudinal strain (LS) to Stage B heart failure (SBHF) criteria (structural or systolic abnormality) improves prediction of symptomatic HF in participants of the SCReening Evaluation of the Evolution of New Heart Failure study, a self-selected population at increased cardiovascular disease risk recruited from members of a health insurance fund in Melbourne and Shepparton, Australia. Both American Society of Echocardiography and European Association of Cardiovascular Imaging (ASE/EACVI) criteria and age-specific Atherosclerosis Risk in Communities (ARIC) study criteria, for SBHF and DD, and ARIC criteria for abnormal LS, were examined. Methods and results: Inclusion criteria were age ≥60 years with one or more of self-reported ischaemic or other heart disease, irregular or rapid heart rhythm, cerebrovascular disease, renal impairment, or treatment for hypertension or diabetes for ≥2 years. Exclusion criteria were known HF, or ejection fraction mild valve abnormality detected on previous echocardiography or other imaging. Echocardiography was performed in 3190 participants who were followed for a median of 3.9 (interquartile range: 3.4, 4.5) years after echocardiography. Symptomatic HF was diagnosed in 139 participants at a median of 3.1 (interquartile range: 2.1, 3.9) years after echocardiography. ARIC structural, systolic, and diastolic abnormalities predicted HF in univariate and multivariable proportional hazards analyses, whereas ASE/EACVI structural and systolic, but not diastolic, abnormalities predicted HF. ARIC and ASE/EACVI SBHF criteria predicted HF with sensitivities of 81% and 55%, specificities of 39% and 76%, and C statistics of 0.60 (95% confidence interval: 0.57, 0.64) and 0.66 (0.61, 0.71), respectively. Adding ARIC DD to SBHF increased sensitivity to 94% with specificity of 24% and C statistic of 0.59 (0.57, 0.61), whereas addition of ASE/EACVI DD to SBHF increased sensitivity to 97% but reduced specificity to 9% and the C statistic to 0.52 (0.50, 0.54, P < 0.0001). Addition of LS to ARIC or ASE/EACVI SBHF criteria had minimal impact on prediction of HF. Conclusions: Age-specific ARIC DD criteria, but not ASE/EACVI DD criteria, predicted symptomatic HF, and addition of age-specific ARIC DD criteria to ARIC SBHF criteria improved prediction of symptomatic HF in asymptomatic individuals with cardiovascular disease risk factors. Addition of LS to ASE/EACVI or ARIC SBHF criteria did not improve prediction of symptomatic HF

Risk factors for incident heart failure with preserved or reduced ejection fraction, and valvular heart failure, in a community-based cohort

Background: The lack of effective therapies for heart failure with preserved ejection fraction (HFpEF) reflects an incomplete understanding of its pathogenesis. Design: We analysed baseline risk factors for incident HFpEF, heart failure with reduced ejection fraction (HFrEF) and valvular heart failure (VHF) in a community-based cohort. Methods: We recruited 2101 men and 1746 women =60 years of age with hypertension, diabetes, ischaemic heart disease (IHD), abnormal heart rhythm, cerebrovascular disease or renal impairment. Exclusion criteria were known heart failure, left ventricular ejection fraction mild in severity. Median follow-up was 5.6 (IQR 4.6-6.3) years. Results: Median time to heart failure diagnosis in 162 participants was 4.5 (IQR 2.7-5.4) years, 73 with HFpEF, 53 with HFrEF and 36 with VHF. Baseline age and amino-terminal pro-B-type natriuretic peptide levels were associated with HFpEF, HFrEF and VHF. Pulse pressure, IHD, waist circumference, obstructive sleep apnoea and pacemaker were associated with HFpEF and HFrEF; atrial fibrillation (AF) and warfarin therapy were associated with HFpEF and VHF and peripheral vascular disease and low platelet count were associated with HFrEF and VHF. Additional risk factors for HFpEF were body mass index (BMI), hypertension, diabetes, renal dysfunction, low haemoglobin, white cell count and ß-blocker, statin, loop diuretic, non-steroidal anti-inflammatory and clopidogrel therapies, for HFrEF were male gender and cigarette smoking and for VHF were low diastolic blood pressure and alcohol intake. BMI, diabetes, low haemoglobin, white cell count and warfarin therapy were more strongly associated with HFpEF than HFrEF, whereas male gender and low platelet count were more strongly associated with HFrEF than HFpEF. Conclusions: Our data suggest a major role for BMI, hypertension, diabetes, renal dysfunction, and inflammation in HFpEF pathogenesis; strategies directed to prevention of these risk factors may prevent a sizeable proportion of HFpEF in the community. Trial registration number: NCT00400257, NCT00604006 and NCT01581827