eplerenone and Heart-Failure--Systolic

Mineralocorticoid receptor antagonists (MCRA) are part of standard medical therapy for heart failure (HF). The clinical efficacy of MCRA in patients with systolic HF has been proven by randomized clinical trials. The efficacy of this drug group in patients with chronic HF with preserved left ventricular systolic function and the advent and practical introductions of safer new-generation MCRA remain to be answered.. Антагонисты минералокортикоидных рецепторов (АМКР) являются частью стандартной медикаментозной терапии больных с сердечной недостаточностью (СН). Клиническая эффективность АМКР доказана в рандомизированных клинических исследованиях у пациентов с систолической СН. Остается открытым вопрос об эффективности данной группы препаратов у больных с хронической СН с сохраненной систолической функцией левого желудочка, а также появление и внедрение в практику более безопасных АМКР нового поколения.

Topics: Eplerenone; Heart Failure, Systolic; Humans; Mineralocorticoid Receptor Antagonists; Prognosis; Randomized Controlled Trials as Topic; Spironolactone; Treatment Outcome; Ventricular Function, Left

Eplerenone (Inspra®) is a selective mineralocorticoid receptor antagonist (MRA). In the EU, it is approved for use (in addition to standard optimal therapy) to reduce the risk of cardiovascular (CV) mortality and morbidity in adult patients with chronic systolic heart failure (HF) and mild symptoms. This article reviews the efficacy and tolerability of eplerenone in this indication and briefly summarizes its pharmacology. In the EMPHASIS-HF study, relative to placebo, the addition of eplerenone to optimal background therapy significantly reduced the risk of death from CV causes or hospitalization for HF in patients with chronic systolic HF and mild symptoms. Benefits of eplerenone therapy over placebo were also observed in several secondary outcomes, including: death from any cause or hospitalization for HF; death from any cause; hospitalization for any reason; or hospitalization for HF. Eplerenone was generally well tolerated in this study, with the most frequent adverse event being hyperkalaemia, which is a known adverse event of the drug class. Sexual adverse events (e.g. gynecomastia) occurred in <1 % of eplerenone recipients, reflecting the selectivity of eplerenone for mineralocorticoid receptors. Based on these results, European guidelines have been updated and recommend the use of an MRA to reduce the risk of HF hospitalization and premature death in all patients with persisting symptoms (New York Heart Association class II-IV) and a left-ventricular ejection fraction of ≤35 %, despite treatment with ACE inhibitor (or an angiotensin receptor blocker if an ACE inhibitor is not tolerated) and a β-blocker.

Topics: Adult; Device Approval; Drug Interactions; Eplerenone; European Union; Heart Failure, Systolic; Humans; Hyperkalemia; Mineralocorticoid Receptor Antagonists; Randomized Controlled Trials as Topic; Severity of Illness Index; Spironolactone

Heart failure (HF), as a serious health condition, is characterised by the decreasing ability of the heart to pump enough blood around the body. This study compared the effects of spironolactone and eplerenone on the echocardiographic variables of the left ventricular (LV) function in symptomatic patients diagnosed with new-onset systolic HF.. This study was a randomised controlled trial, including 85 symptomatic patients with new-onset systolic HF (namely, dilated cardiomyopathy). The patients were then randomly assigned to two groups in a 1:1 ratio and received either spironolactone or eplerenone in addition to optimal HF therapy for 6 months. Echocardiography was performed to visualise alterations in two-dimensional, pulse Doppler, tissue Doppler, and deformation indices of LV function.. The results revealed that the group receiving eplerenone had a significantly greater increase in LV ejection fraction (LVEF) and a decrease in end-systolic LV internal diameter compared with the group receiving spironolactone (intergroup p=0.002 and p=0.006, respectively). There was a significant reduction in the end-diastolic LV internal diameter and the left atrial diameter, and a significant rise in tissue Doppler peak systolic mitral annular velocity in the group taking eplerenone; there were no significant changes in these variables in the group receiving spironolactone (intergroup p=0.006 and p=0.049, respectively). Accordingly, eplerenone had greater favourable effects on LVEF and the global longitudinal strain than spironolactone (B=5.207 [p<0.001] and B= -2.072 [p=0.044]), respectively.. This study established that adding eplerenone to optimal HF therapy might be associated with more improvements in echocardiographic variables of LV function than spironolactone in symptomatic patients with new-onset systolic HF.

Topics: Echocardiography; Eplerenone; Heart Failure; Heart Failure, Systolic; Humans; Mineralocorticoid Receptor Antagonists; Spironolactone; Ventricular Function, Left

Increased resting heart rate is a risk factor for cardiovascular mortality and morbidity. Mineralocorticoid receptor antagonists (MRAs) have been shown to improve cardiac sympathetic nerve activity, reduce heart rate and attenuate left ventricular remodelling. Whether or not the beneficial effects of MRA are affected by heart rate in heart failure patients with reduced ejection fraction (HFREF) is unclear.. We undertook a secondary analysis of data from the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure study to assess if clinical outcomes, as well as the efficacy of eplerenone, varied according to heart rate at baseline.. High resting heart rate of 80 bpm and above predisposed patients to greater risk of all outcomes in the trial, regardless of treatment allocation. The beneficial effects of eplerenone were observed across all categories of heart rate. Eplerenone reduced the risk of primary endpoint, the composite of cardiovascular death and hospitalisation for heart failure, by 30% (aHR 0.70; 95% CI 0.54-0.91) in subjects with heart rate ≥ 80 bpm, and by 48% (aHR 0.52; 95% CI 0.33-0.81) in subjects with heart rate ≤ 60 bpm. Eplerenone also reduced the risks of hospitalisation for heart failure, cardiovascular deaths and all-cause deaths independently of baseline heart rate.. Baseline heart rate appears to be an important predictor of major clinical outcome events in patients with HFREF, as has been previously reported. The benefits of eplerenone were preserved across all categories of baseline heart rate, without observed heterogeneity in the responses.

Topics: Dose-Response Relationship, Drug; Eplerenone; Europe; Female; Heart Failure, Systolic; Heart Rate; Humans; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Risk Factors; Stroke Volume; Survival Rate; Treatment Outcome; United States

Although hypokalaemia is common among patients with heart failure (HF), the prognostic significance of baseline hypokalaemia and hypokalaemia during follow-up in HF patients receiving a mineralocorticoid receptor antagonist (MRA) remains uncertain.. In HF patients receiving optimal therapy but not treated with eplerenone, baseline hypokalaemia was associated with worse outcomes. Conversely, hypokalaemia amplified the treatment effect of eplerenone.

Topics: Dose-Response Relationship, Drug; Eplerenone; Europe; Female; Follow-Up Studies; Heart Failure, Systolic; Humans; Hypokalemia; Male; Mineralocorticoid Receptor Antagonists; Prognosis; Spironolactone; Survival Rate; Time Factors; Treatment Outcome

An excessive production of aldosterone influences outcome in patients with heart failure (HF) and in obese patients. Findings from laboratory studies suggest that chronic aldosterone blockade maybe more beneficial in abdominally obese HF-prone rats. In the current study, we investigated if the clinical response to a mineralocorticoid receptor antagonist in mildly symptomatic HF patients varied by abdominal obesity.. A total of 2587 NYHA class II, reduced ejection fraction HF (HFrEF) patients enrolled in the EMPHASIS-HF trial were randomly assigned to eplerenone and placebo. In this post hoc analysis, patients were categorized according to waist circumference (WC) (normal if WC < 102 cm in men and < 88 cm in women; abdominal obesity if WC ≥ 102 cm in men and ≥ 88 cm women). The potential statistical interaction between the treatment and WC was assessed on the primary endpoint of death from cardiovascular causes or hospitalization for HF and other secondary endpoints. Over a median follow-up of 21 months, a significant benefit of eplerenone for the primary outcome was noted in both normal [hazard ratio (HR) 0.77, 95% confidence interval (CI) 0.61-0.98, P = 0.03] and increased (HR 0.48, 95% CI 0.37-0.63, P < 0.0001) WC subgroups, but the latter patients appeared to receive greater benefit than patients with normal WC (P for interaction = 0.01). This suggests a significant quantitative (treatment effect varies in magnitude by subgroup, but is always in same direction) rather than a qualitative interaction (direction of the treatment effect varies by subgroup) between eplerenone and WC in the adjusted analysis. Mean doses of eplerenone, blood pressure and serum potassium changes and adverse events were similar between WC subgroups.. In EMPHASIS-HF, eplerenone improved outcomes in HFrEF patients with and without abdominal obesity, although the benefit appeared to be more pronounced among those with abdominal obesity. The findings are potentially hypothesis generating and need to be replicated in other HFrEF populations.

Topics: Aged; Aldosterone; Drug Monitoring; Eplerenone; Female; Heart Failure, Systolic; Humans; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Obesity, Abdominal; Spironolactone; Stroke Volume; Treatment Outcome; Ventricular Dysfunction, Left

Cardiovascular hospitalization (CVH) in patients with heart failure (HF) is associated with a high post-discharge rate of early re-admission and CV death. Eplerenone might be effective in reducing the incidence of these adverse clinical outcomes during this period.. The EMPHASIS-HF trial compared eplerenone with placebo added to standard therapy in 2737 patients with New York Heart Association class II HF and left ventricular ejection fraction ≤35%. We conducted a post hoc analysis in the 2338 patients randomized within 180 days of a CVH. The interaction between the time from the qualifying CVH to randomization and the primary outcome of CV death or hospitalization for HF (HHF), as well as other secondary outcomes, was assessed in Cox survival models. Most of the qualifying CVHs were HHF (N = 1496, 64.0%), acute coronary syndromes (N = 390, 16.7%), and arrhythmias (N = 197, 7.2%). The median time of study drug initiation from qualifying CVH was 42 days. The relative rate reductions in CV death/HHF, HHF, and all-cause mortality were similar (P for interaction = 0.65, 0.44, and 0.40, respectively) whether the treatment was initiated <42 or 42+ days after qualifying CVH. Absolute rate reductions were -5.61 [-8.67, -2.55] events per 100 patient × years in the <42 days group and -3.58 [-6.37, -0.79] in the 42+ days group. The adverse effects of eplerenone were also unaffected by the time from the qualifying CVH.. Eplerenone is safe, improves survival, and may prevent re-admission when initiated soon after a hospitalization for HF or acute coronary syndromes in patients with systolic HF and mild symptoms.

Topics: Acute Coronary Syndrome; Aged; Eplerenone; Female; Follow-Up Studies; Heart Failure, Systolic; Hospitalization; Humans; Hyperkalemia; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Patient Readmission; Secondary Prevention; Spironolactone; Treatment Outcome

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.. 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).. 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.

Topics: Aged; Cost-Benefit Analysis; Drug Costs; Eplerenone; Health Expenditures; Heart Failure, Systolic; Humans; Mineralocorticoid Receptor Antagonists; Patient Simulation; Quality of Life; Severity of Illness Index; Spain; Spironolactone; United Kingdom; Ventricular Function, Left

Our objective was to create a simple prognostic risk score for patients with systolic heart failure and mild symptoms. We then assessed the efficacy of eplerenone across different categories of risk.. The Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure trial (EMPHASIS-HF) was an international randomized trial, comparing eplerenone with placebo in 2737 patients with systolic heart failure and mild symptoms. The primary outcome was a composite of cardiovascular death or hospitalization for heart failure, over a median 2.1 years follow-up. Using multivariable Cox modelling age, sex, systolic blood pressure, estimated glomerular filtration rate, diabetes, BMI, haemoglobin, prior heart failure (HF) hospitalization, prior myocardial infarction/coronary artery bypass surgery (CABG), and heart rate were identified as strong independent risk factors. Estimates from the model were converted into a simple integer risk score which was categorized into three groups of low-, medium-, and high risk. In placebo patients, the rates (per 100 patient-years) for the primary outcome were 7.6, 19.0, and 39.4 in the low-, medium-, and high-risk groups, respectively. On eplerenone, these rates were reduced to 5.6, 12.2, and 24.2, respectively. Eplerenone was beneficial across all risk categories and the hazard ratios were similar. The absolute treatment benefit was greatest among those at highest risk. Similar patterns emerged for all-cause mortality and for all HF hospitalizations.. This easy-to-use integer risk score should be of value in quantifying individual patient risk in patients with systolic HF and mild symptoms. The relative benefits of eplerenone appeared consistent across the whole spectrum of risk, including those at lower risk.

Topics: Adult; Aged; Death, Sudden, Cardiac; Eplerenone; Female; Heart Failure, Systolic; Hospitalization; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Prognosis; Proportional Hazards Models; Risk Assessment; Spironolactone

Several clinical trials have shown that in patients with acute myocardial infarction (MI), statin therapy improves cardiovascular (CV) outcomes, but in these trials patients with acute heart failure (HF) were excluded or only a few were included. In patients with chronic HF, statin therapy does not reduce all-cause or CV mortality. We aimed to assess the association between statin therapy and clinical outcomes in the setting of acute HF with systolic dysfunction complicating acute MI.. We performed a post-hoc analysis in 6632 patients included in the EPHESUS trial. The mean age of patients was 64 years and 71% were male. Overall, 47% of patients had a statin prescribed at baseline. Cox regression models and a secondary analysis using propensity score matching were fit to assess the association between statin prescription and clinical outcomes. During a mean follow-up of 16 ± 7 months, all-cause death occurred in 385 (12%) patients with and in 647 (18%) patients without a statin (P < 0.001). After extensive adjustment, the risk of all-cause death was 20% lower in patients on statin [hazard ratio (HR) 0.80, 95% confidence interval (CI) 0.69-0.92, P = 0.001]. This positive association was mostly due to a lower risk of CV death (HR 0.76, 95% CI 0.65-0.88, P = 0.0002). In contrast, statin use was associated with a higher risk of non-CV hospitalizations (HR 1.16, 95% CI 1.02-1.33, P = 0.02).. Our results suggest that patients with acute HF complicating acute MI may benefit from being on statin therapy. Prospective clinical trials are required to validate these findings.

Topics: Acute Disease; Aged; Double-Blind Method; Drug Therapy, Combination; Eplerenone; Female; Heart Failure, Systolic; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Myocardial Infarction; Propensity Score; Spironolactone; Stroke Volume; Survival Analysis; Treatment Outcome; United States

We evaluated the effect of the selective mineralocorticoid receptor antagonist eplerenone on renal function and the interaction between changes in renal function and subsequent cardiovascular outcomes in patients with heart failure and left ventricular systolic dysfunction after an acute myocardial infarction in the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS).. Serial changes in estimated glomerular filtration rate (eGFR) were available in 5792 patients during a 24-month follow-up. Patients assigned to eplerenone had a decline in eGFR with an adjusted mean difference of -1.4±0.3 mL · min(-1) · 1.73 m(-2) compared with placebo (P<0.0001), an effect that appeared within the first month (-1.3±0.4 mL · min(-1) · 1.73 m(-2)) and persisted throughout the study. Overall, 914 patients experienced a decline in eGFR >20% in the first month, 16.9% and 14.7% in the eplerenone and placebo groups, respectively (odds ratio, 1.15; 95% confidence interval, 1.02-1.30; P=0.017). In multivariate analyses, determinants of this early decline in eGFR were female sex, age ≥65 years, smoking, left ventricular ejection fraction <35%, and use of eplerenone and loop diuretic. An early decline in eGFR by >20% was associated with worse cardiovascular outcomes independently of baseline eGFR and of the use of eplerenone, which retained its prognostic benefits even under these circumstances.. In patients with heart failure after acute myocardial infarction and receiving standard medical care, an early decline in eGFR is not uncommon and is associated with poor long-term outcome. Eplerenone induced a moderately more frequent early decline in eGFR, which did not affect its clinical benefit on cardiovascular outcomes.

Topics: Aged; Eplerenone; Glomerular Filtration Rate; Heart Failure; Heart Failure, Systolic; Humans; Kidney; Middle Aged; Mineralocorticoid Receptor Antagonists; Myocardial Infarction; Prognosis; Spironolactone; Treatment Outcome; Ventricular Dysfunction, Left

The purpose of this study was to analyze the incidence of new atrial fibrillation or flutter (AFF) in the EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization And SurvIval Study in Heart Failure) database.. Aldosterone antagonism in heart failure might influence atrial fibrosis and remodeling and, therefore, risk of developing AFF. The development of new AFF was a pre-specified secondary endpoint in the EMPHASIS-HF study.. Patients in New York Heart Association functional class II and with ejection fraction ≤35% were eligible for EMPHASIS-HF. History of AFF at baseline was reported by investigators using the study case report form. New onset AFF (in those with no history of AFF at baseline) was reported using a specific endpoint form; in a sensitivity analysis we also examined the effect of eplerenone on AFF reported as an adverse event.. New onset AFF was significantly reduced by eplerenone: 25 of 911 (2.7%) versus 40 of 883 (4.5%) in the placebo group (hazard ratio [HR]: 0.58, 95% confidence interval [CI]: 0.35 to 0.96; p = 0.034). The reduction in the primary endpoint with eplerenone was similar among patients with and without AFF at baseline (HR: 0.60, 95% CI: 0.46 to 0.79 vs. HR: 0.70, 95% CI: 0.57 to 0.85, respectively; p for interaction = 0.41). The risk of cardiovascular (CV) death or hospital admission for worsening heart failure, the primary endpoint, was not significantly different in subjects with and without AFF at baseline (both study groups combined: HR: 1.23, 95% CI: 0.81 to 1.86; p = 0.33).. In patients with systolic heart failure and mild symptoms, eplerenone reduced the incidence of new onset AFF. The effects of eplerenone on the reduction of major CV events were similar in patients with and without AFF at baseline.

Topics: Aged; Atrial Fibrillation; Disease Progression; Dose-Response Relationship, Drug; Electrocardiography; Eplerenone; Female; Heart Failure, Systolic; Heart Rate; Hospitalization; Humans; Incidence; Male; Mineralocorticoid Receptor Antagonists; Prognosis; Spironolactone; Survival Rate; United States

In chronic heart failure (HF), aldosterone antagonists have been shown to improve survival in patients with low ejection fraction and moderate-to-severe symptoms [New York Heart Association (NYHA) classes III and IV]. Efficacy of these agents was also shown when they were administered to patients with left ventricular dysfunction and signs and symptoms of CHF early after acute myocardial infarction. It is not known whether the selective aldosterone antagonist eplerenone can improve outcomes in mildly symptomatic patients. The Eplerenone in Mild Patients Hospitalization And SurvIval Study in Heart Failure (EMPHASIS-HF) was designed to evaluate the effect of eplerenone on mortality and morbidity in patients with chronic systolic HF in NYHA class II. Methods Approximately 3100 patients with ejection fraction < or =30% and estimated glomerular filtration rate > or =30 mL/min/1.73 m(2) will be recruited. Patients are randomized 1:1 to double-blind eplerenone or placebo in addition to standard chronic HF therapy. Doses are adjusted from 25 mg every other day to 50 mg daily, depending on serum potassium. The primary endpoint is a composite of time to cardiovascular death or first hospital admission for worsening HF, whichever occurs first.. The study will be complete when approximately 813 subjects experience a primary endpoint. Clinical Trials.gov. NCT00232180.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Double-Blind Method; Eplerenone; Heart Failure, Systolic; Hospitalization; Humans; Mineralocorticoid Receptor Antagonists; Research Design; Spironolactone; Survival Analysis

Patients with heart failure with reduced ejection fraction (HFrEF) and insulin-treated diabetes have a high risk of cardiovascular complications. Mineralocorticoid receptor antagonists may mitigate this risk. We aim to explore the effect of eplerenone on cardiovascular outcomes and all-cause mortality in HFrEF patients with diabetes, including those treated with insulin in the EMPHASIS-HF trial (Eplerenone in Patients with Systolic Heart Failure and Mild Symptoms).. The primary outcome was the composite of heart failure hospitalization or cardiovascular death. Cox models with treatment-by-diabetes subgroup interaction terms were used.. The median follow-up was 21 (10-33) months. Of the 2737 patients included, 623 (23%) had non-insulin-treated diabetes, 236 (9%) had insulin-treated diabetes and 1878 did not have diabetes. Patients with insulin-treated diabetes were younger, more often women, with higher body mass index, waist circumference, more frequent ischemic heart failure cause, impaired kidney function, and longer diabetes duration. Compared with patients without diabetes, those with insulin-treated diabetes had a 2-fold higher risk of having a primary outcome event. The hazard ratio (95% CI) for the effect of eplerenone, compared with placebo, on the primary outcome was 0.31 (0.19-0.50) in insulin-treated diabetes, 0.69 (0.50-0.93) in non-insulin-treated diabetes, and 0.72 (0.58-0.88) in patients without diabetes; interaction. Patients with insulin-treated diabetes experienced a greater benefit from eplerenone than those with diabetes not treated with insulin and people without diabetes. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00232180.

Topics: Aged; Diabetes Mellitus; Eplerenone; Female; Heart Failure; Heart Failure, Systolic; Humans; Insulins; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Risk Factors; Spironolactone; Treatment Outcome

Visit-to-visit office blood pressure (BP) variability (BPV) has been associated with morbidity and mortality outcomes in several cardiovascular conditions. The aim of this study was to evaluate the association between BPV and outcomes in patients with heart failure and reduced ejection fraction and the effect of eplerenone on BPV.. We evaluated the associations between BPV, calculated as SBP coefficient of variation (SBP-CoV = SD/mean × 100%), and the primary composite endpoint of cardiovascular mortality or heart failure hospitalization (HFH), and its components, in 2549 patients from the Eplerenone in Patients with Systolic Heart Failure and Mild Symptoms trial. Lower SBP-CoV was independently associated with a higher risk of all the studied outcomes, while higher as well as lower SBP-CoV were associated with a higher risk of cardiovascular death. After a median follow-up period of 21 months the risk of the composite outcome of cardiovascular death or HFH was almost double in the lower SBP-CoV tertile as compared with the intermediate tertile [adjusted hazard ratio: 2.01, 95% confidence interval (1.62-2.51), P < 0.001]. The relationship between SBP-CoV and outcomes was not modified by eplerenone (P value for interaction = 0.48). An interaction was detected between mean SBP and SBP-CoV for the primary outcome (P = 0.048) and for HFH (P = 0.018). The effect modification was slight, but lower SBP-CoV was associated with worse outcomes in patients with both low and high SBP, while this interaction was less clear for patients with SBP in the 'normal' range.. In our patients with heart failure and reduced ejection fraction and mild symptoms, both a lower and higher SBP-CoV were associated with worse outcomes. SBP-CoV did not modify the benefit of eplerenone. Further studies are warranted to clarify the role of BPV in heart failure. CLINICALTRIALS.. NCT00232180.

Topics: Aged; Blood Pressure; Blood Pressure Determination; Cardiovascular Diseases; Eplerenone; Female; Heart Failure, Systolic; Hospitalization; Humans; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Office Visits; Prognosis; Proportional Hazards Models; Randomized Controlled Trials as Topic; Stroke Volume; Ventricular Dysfunction, Left

It is not known whether concomitant use of aspirin might attenuate the beneficial effects of mineralocorticoid receptor antagonists (MRAs). The purpose of this subgroup analysis was to explore the interaction between baseline aspirin treatment and the effect of eplerenone on the primary efficacy outcomes (composite of hospitalization for heart failure or cardiovascular mortality), its components, and safety markers [estimated glomerular filtration rate (eGFR), systolic blood pressure (SBP), and serum potassium >5.5 mmol/L] in the Eplerenone in Mild Patients Hospitalization and SurvIval Study in Heart Failure trial (EMPHASIS-HF).. Patients with chronic heart failure, reduced ejection fraction (HFREF), and mild symptoms were enrolled in EMPHASIS-HF. We evaluated baseline characteristics according to aspirin use. We explored the interaction between aspirin and eplerenone, using Cox proportional hazards models providing adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) and P-values for interaction. Of the 2737 patients randomized, 1605 patients (58.6%) were taking aspirin. The beneficial effects of eplerenone on the primary endpoint were similar in patients not treated (adjusted HR 0.59, 95% CI 0.46-0.75) or treated (adjusted HR 0.71, 95% CI 0.59-0.87) with aspirin at baseline (interaction P-value = 0.19). We did not observe any significant modification of the safety markers by aspirin that was clinically meaningful.. Aspirin use in patients with chronic systolic heart failure and mild symptoms did not substantially reduce the overall beneficial effects of the MRA eplerenone contrary to what has been described in some studies with ACE inhibitors.

Topics: Aged; Aspirin; Blood Pressure; Chronic Disease; Drug Interactions; Eplerenone; Female; Glomerular Filtration Rate; Heart Failure, Systolic; Humans; Male; Mineralocorticoid Receptor Antagonists; Platelet Aggregation Inhibitors; Potassium; Proportional Hazards Models; Spironolactone; Stroke Volume

Eplerenone has been demonstrated as being cost effective for the treatment of patients with systolic heart failure (HF) and mild symptoms in several jurisdictions; however, its cost effectiveness is unknown in the context of Alberta, Canada.. We used a discrete-event simulation model to compare costs and outcomes between standard care and standard care plus eplerenone for the treatment of HF with mild symptoms. We used Alberta data (whenever possible) together with a healthcare perspective, a lifetime horizon, and 3 % annual discount rate for analyses.. Clinically, eplerenone prevented HF hospitalizations, atrial fibrillations, and cardiovascular (CV) deaths, but incurred more adverse events and device implantations than standard care. The remaining life of patients receiving eplerenone was 7.08 versus 5.83 years for those receiving standard care. Eplerenone gained 1.25 life-years and 1.18 quality-adjusted life-years (QALYs), with an incremental cost of $Can7200. Therefore, the incremental cost-effectiveness ratio (ICER) was $Can5700 per life-year gained and $Can6100 per QALY gained.. Given the most cited ICER threshold is $Can50,000, the use of eplerenone as an adjunct to standard care for treating patients with systolic HF and mild symptoms is cost effective in the context of Alberta. Eplerenone would cost the Alberta health system about $Can4.6 million a year in drug costs. Incorporating reductions in health services utilization associated with eplerenone, the budget impact is smaller. For the first year, the use of eplerenone is cost saving and for 5 years the cost is approximately $Can6 million.

Topics: Aged; Aged, 80 and over; Alberta; Cost-Benefit Analysis; Drug Costs; Drug-Related Side Effects and Adverse Reactions; Eplerenone; Female; Heart Failure, Systolic; Humans; Male; Mineralocorticoid Receptor Antagonists; Quality-Adjusted Life Years; Spironolactone

Postoperative atrial fibrillation (POAF) is the most common arrhythmia after cardiac surgery. There exist consistent experimental and clinical data suggesting that aldosterone antagonists (AAs) may exert beneficial effects regarding electrical and structural remodeling in failing myocardium. Recently, eplerenone (EPL) has been found to reduce the incidence of nonsurgical AF when added to guideline-recommended therapy in patients with systolic heart failure. Based on these findings, we primarily aimed to evaluate by retrospective analysis the impact of the two AAs, EPL and spironolactone (SPL), given at standard therapeutic doses in preventing new-onset POAF in patients the majority of which had a preoperative ejection fraction (EF) below 40%. A total of 332 patients (298 men/34 women, mean age 64.3 ± 9 years) without history of AF were included in this analysis; 132 of these patients received long-term EPL or SPL in addition to beta-blockade/statins therapy and 200 patients received neither EPL nor SPL. All patients underwent on-pump coronary artery bypass graft (80%) and/or valvular surgery (20%). In the nonAA group (EF = 35.8 ± 6%) 90/200 patients (45%) had POAF, while in the AA group (EF = 36.2 ± 5%) only 40/132 patients (30.3%) developed POAF (P < 0.01, χ (2) test). Multivariate logistic regression analysis revealed that only AAs and left atrial diameter significantly affected the development of POAF even when adjusted for other clinical variables (P < 0.05). In conclusion, AAs significantly reduced the incidence of POAF when added to standard heart failure therapy in patients undergoing on-pump cardiac surgery.

Topics: Aged; Atrial Fibrillation; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Chi-Square Distribution; Coronary Artery Bypass; Eplerenone; Female; Greece; Heart Failure, Systolic; Heart Valves; Humans; Incidence; Logistic Models; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Multivariate Analysis; Odds Ratio; Retrospective Studies; Risk Factors; Spironolactone; Stroke Volume; Time Factors; Treatment Outcome; Ventricular Function, Left

Topics: Chronic Disease; Eplerenone; Evidence-Based Medicine; Heart Failure, Systolic; Humans; Hyperkalemia; Mineralocorticoid Receptor Antagonists; Spironolactone

Chronic heart failure (CHF) remains an important cause of morbidity and mortality worldwide. Currently, there are no cost-effectiveness studies of eplerenone use in patients with New York Heart Association (NYHA) class II CHF.. We sought to evaluate the cost effectiveness of eplerenone compared with placebo in patients with chronic systolic heart failure and NYHA class II symptoms.. A 10-year Markov model with yearly cycles was constructed to evaluate the cost effectiveness of eplerenone compared with placebo, based on data from the EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization And Survival Study in Heart Failure) study. The model classified subjects into two health states: 'Alive with CHF' and 'Dead'. Information about the cost of disease was derived from Australian Refined Diagnosis-Related Groups (AR-DRG) data. The cost of eplerenone was taken from the Australian Pharmaceutical Benefit Scheme. Utility data were derived from published sources, and a 5 % annual discount rate was applied to future costs and benefits. Over 10 years, and compared with placebo, the model predicted that eplerenone would lead to a saving of 0.5 life-years (discounted) and 0.4 quality-adjusted life-years (QALYs) per person. The net cost was (in Australian dollars [$A]) $A6,117 (discounted) per person. These equated to incremental cost-effectiveness ratios of $A12,024 per life-year saved and $A16,700 per QALY saved. Sensitivity analyses indicated that these results were robust.. Eplerenone may represent a cost-effective strategy for preventing morbidity and mortality among patients with chronic systolic heart failure and NYHA class II symptoms.

Topics: Age Factors; Aged; Australia; Chronic Disease; Cost-Benefit Analysis; Eplerenone; Female; Heart Failure, Systolic; Humans; Male; Markov Chains; Middle Aged; Mineralocorticoid Receptor Antagonists; Models, Economic; Quality-Adjusted Life Years; Racial Groups; Sex Factors; Spironolactone

Eplerenone is known to reduce time to first hospitalization for heart failure or cardiovascular death in patients with heart failure and mild symptoms. In chronic diseases such as heart failure, characterized by repeat hospitalizations, analyzing all heart failure hospitalizations, not just the first, should give a more complete picture of treatment benefits.. The Eplerenone in Mild Patients Hospitalization and SurvIval Study in Heart Failure (EMPHASIS-HF) trial compared eplerenone with placebo in 2737 patients with mild heart failure, followed for a median 2.08 years (interquartile range, 1.08-3.10 years). Data were collected on all hospitalizations, with a focus on those due to heart failure. Heart failure hospitalization rates in the eplerenone and placebo groups were 10.70 and 16.99 per 100 patient-years, respectively. Allowing for skewness in the frequency of hospitalizations by using the negative binomial generalized linear model, the rate ratio (eplerenone versus placebo) was 0.53 (95% confidence interval, 0.42-0.66; P<0.0001). A plot of cumulative hospitalization rates over time revealed that most of the reduced risk on eplerenone occurred in the first year of follow-up. Several baseline variables strongly predicted the risk of hospitalization. More complex statistical methods, adjusting for mortality (as informative censoring), made a negligible difference in these findings.. Eplerenone markedly reduces the risk of heart failure hospitalizations in patients with heart failure and mild symptoms to a greater extent than is captured by only studying the time to first hospitalization. Future clinical trials in heart failure would gain from incorporating repeat hospitalizations into their primary evaluation of treatment effects.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00232180.

Topics: Aged; Eplerenone; Follow-Up Studies; Heart Failure, Systolic; Hospitalization; Humans; Incidence; Linear Models; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Regression Analysis; Risk Factors; Spironolactone; Time Factors

The recent publication of the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF) has affirmed the important role of aldosterone-receptor antagonism across the spectrum of systolic heart failure. Previously restricted as therapy in patients with severe symptomatic or postinfarction heart failure, it now is being considered in less-sick patients. The precise mechanisms of benefit remain to be elucidated, in part due to the observed discrepancy between improved outcomes and the lack of reverse cardiac remodeling with aldosterone-receptor antagonists. With the probable increased use of spironolactone and eplerenone, there are concerns for increased complications, especially hyperkalemia. This risk must be balanced against the potential benefit for reduced mortality and morbidity in addition to effects of β-blockers and angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers, and cardiac resynchronization therapy.

Topics: Eplerenone; Heart Failure, Systolic; Humans; Mineralocorticoid Receptor Antagonists; Patient Selection; Randomized Controlled Trials as Topic; Research Design; Severity of Illness Index; Spironolactone; Treatment Outcome; Ventricular Remodeling