Atrial fibrillation af and heart failure hf are global epidemics that began more than a century ago, and their association with an ageing general population has brought about an increase in cardiovascular morbidity and rising healthcare costs. Pdf eplerenone in patients with systolic heart failure. Metoprolol crxl randomised intervention trial in congestive heart failure merithf. Cardiovascular cv diseases in general and heart failure hf in particular are major contributors to death and morbidity and are also recognized as important drivers of health care expenditure. Dec 01, 2020 comparison of overall survival in the rales and emphasis hf trials supported these findings, with the sicker, less welltreated patients in the rales study having a nnt at 3 years to prevent 1 death of only 12 patients, compared with 33 patients in the emphasis hf trial, despite similar relative risk reductions of 0. In his editorial, armstrong suggests that the 37% reduction in the composite end point in emphasis hf seems surprisingly large for a trial of mildly symptomatic patients, but then he points out. In short, emphasis hf was a randomized, doubleblind trial in which 2,737 patients in nyha functional class ii and with lvef. The purpose of the emphasis hf trial was to explore the effects of. Costeffectiveness of eplerenone in patients with systolic.
However, despite the publication of rales in severe systolic hf in 1999, and the publication of the ephesus trial in 2003. In this randomized, doubleblind trial, we randomly assigned 2737 patients with new york heart. Pdf clinical benefits of eplerenone in patients with. The emphasishf trial demonstrated a statistically significant 37% relative risk. Implications of emphasishf for clinical practice the medical. Emphasis hf from 2006 to 2010, the eplerenone in mild patients hospitalization and survival study in heart failure emphasis hf. Study in heart failure emphasis hf, which used another mra, eplerenone, in patients with an ef,35% and nyha classiisymptoms23,a37%relativerisk reduction was seen for cv death or hospitalization for heart failure in the eplerenonetreated group. Pdf eplerenone in patients with systolic heart failure and. Study design emphasis hf is a multicentre, randomized, doubleblind, placebocontrolled. The more recent eplerenone in mild patients hospitalization and survival study in heart failure emphasis hf was carried out on patients with less severe hf class iiiii nyha. Emphasis hf studied patients with nyha class ii symptoms, and most were receiving betablockers 85% vs. Electronic health recordleveraged, patientcentered. Jan 01, 2017 heart failure is an increasingly common condition resulting in high rates of morbidity and mortality.
More than half a century ago, hans selye, one of the grandfathers of stress and steroid hormone research, observed in a small 1960 study that spironolactone substantially. Patients randomized to usual care n 448 had hf care in accordance with published guidelines, with emphasis on titration of. The aim of our eplerenone in mild patients hospitalization and survival study in heart failure emphasis hf was to investigate the effects of eplerenone, added to evidencebased therapy, on. Recent landmark drug trials in heart failure management. Study patientsthe design of the emphasis hf trial has been published in detail, 6 and the trial protocol and statistical analysis plan are available at. Heart failure epidemiology heart failure hf affects 6. Patients randomized to the guided strategy n 446 had hf therapy titrated with the goal of achieving a target ntprobnp of less than pgml. Nnt of to prevent 1 composite endpoint of death from cv causes or first. The primary outcome was a composite of death from cardiovascular causes or hospitalization for heart failure. Survival study in heart failure emphasis hf david preiss 1,dirkj. Phase iii randomized trial in 2,737 patients with nyha class ii heart failure.
The term gamechanger is overused but may be appropriate for the dapahf trial on the sglt2 inhibitor dapagliflozin in patients with heart failure and reduced ejection fraction. Effect of eplerenone in patients with heart failure and reduced. The recently reported dapagliflozin and prevention of adverse outcomes in heart failure trial dapahf showed the sodiumglucose cotransporter 2 sglt2 inhibitor dapagliflozin reduced the risk of hospital admission for worsening heart failure, increased survival and improved symptoms in patients with heart failure with reduced ejection fraction hfref. Oct 04, 2005 a comparison of outcomes in patients in new york heart association nyha class ii heart failure when treated with eplerenone or placebo in addition to standard heart failure medicines emphasis hf the safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Types of heart failure american college of physicians. Solvd, charm, merithf, scdheft, shift systolic heart failure treatment with the if inhibitor ivabradine trial, emphasis hf, paradigmhf, dapahf, victoria, and emperorreduced emperorred. Eplerenone for nyha class ii heart failure herts valleys ccg. Eplerenone and newonset diabetes in patients with mild heart. Clinical benefit of eplerenone in patients with mild. Phase 3 dreamhf trial of mesenchymal precursor cells in. Contemporary management of heart failure in patients with. Survival study in heart failure emphasis hf is to investigate the effects of eplerenone vs. Three main regional centers in the uchealth system will participate in a twoarm, randomized study design. Study patientsthe design of the emphasis hf trial has been published in detail, 6 and the trial protocol and.
Patients remained within these dose ranges during the trial. For patients who have heart failure and reduced ejection fraction, randomized clinical trials. Study design and patient population the design and main results of the emphasis hf trial have been reported previously. Clinical benefits of eplerenone in patients with systolic heart failure. In that study approximately 30% of the patients in eacharmhaddiabetes23. Clinical benefit of eplerenone in patients with mild symptoms. Rationale and design of the eplerenone in mild patients. Diabetes and incident heart failure in the us framingham study risk of hf in diabetics 2x diabetic males 5x diabetic females 4x young diabetic males 8x young diabetic females us hmo prevalence study with diabetes, incident hf developed at a rate of 3. The 1999 rales trial revealed that the addition of spironolactone a nonselective aldosterone antagonist to usual medical care. Effect of metoprolol crxl in chronic heart failure. Study shows epleronone to reduce atrial fibrillation. The design of the emphasis hf trial has been published in detail,6 and the trial protocol and statistical analysis plan are available at. Pdf critical questions about paradigmhf and the future. Consistency was predefined as a point estimate of the hazard ratio study design the study was a multicenter, randomized, doubleblind placebocontrolled, parallelgroup study j emphasis hf.
Eplerenone and standard therapy cut mortality 24% in mild. Patients randomized to usual care n 448 had hf care in accordance with published guidelines, with emphasis on titration of proven neurohormonal therapies for hf. Patients remained within these dose ranges during the trial as per stratification. Sep 14, 2012 backgroundin emphasis hf eplerenone in mild patients hospitalization and survival study in heart failure, eplerenone significantly reduced major cardiovascular events versus placebo in 2737 patients with mild symptoms of heart failure and an ejection fraction of trial, a multicentre phase iib dosefinding study in patients with worsening hfref and coexisting moderate chronic kidney disease andor type 2 diabetes mellitus. Emphasis hf comparison of outcomes in patients in nyha class ii heart failure when treated with eplerenone or placebo in addition to standard heart failure medicines enos endothelial no synthase fda food and drug administration hf heart failure hfmace heart failurerelated major adverse cardiac event hfref heart failure with reduced ejection. Eplerenone reduced the risk of cardiovascular death or heart failure hospitalization by 37%, compared with placebo. The emphasis hf eplerenone in mild patients hospitalization and survival study is summarized in this section including the primary endpoint and results. Adding inspra eplerenone to standard therapy significantly. Eplerenone and newonset diabetes in patients with mild. Dec 03, 2017 emphasis hf studied patients with nyha class ii symptoms, and most were receiving betablockers 85% vs. 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 emphasis. In this cross trial analysis, we estimated treatment effects of comprehensive diseasemodifying pharmacological therapy arni.
Emphasishf eplerenone in mild patients hospitalization and survival study in heart failure. Carresshf study changes from baseline in serum creatinine and body weight at various time points, according to treatment group 188 patients randomized to either ultrafiltration or high dose diuretic. The purpose of the emphasis hf trial was to explore the effects of adding eplerenone, a type of mineralocorticoid antagonist, to evidencebased therapy in patients with systolic heart failure and only mild symptoms i. Nov 07, 2017 the epichf study will test the effectiveness of a patient empowerment and activation for optimization of heart failure with reduced ejection fraction hfref medication plans. All analyses were performed or replicated independently at the london school of hygiene and tropical medicine tim collier. Emphasishf trial in nyha class ii chronic heart failure.
Results efficacy after a median followup of 21 months, the trial was stopped early because of a significant benefit in the eplerenone group there was a 37% reduction in the primary end point, a 24% reduction in cv death, and a 42% reduction in hospitalization for hf the main side effect was hyperkalemia, with potassium. Diabetes in patients hospitalized with heart failure. The eplerenone in mild patients hospitalization and survival study in heart failure emphasis hf trial compared eplerenone with placebo in. Eplerenone is not superior to older and less expensive. Mineralocorticoid antagonists significantly improved survival in patients with severe systolic heart failure i. Dapagliflozin and prevention of adverse outcomes in heart. Hf, the target dose of eplerenoneplacebo was stratified at randomization according to estimated glomerular filtration rate egfr. The primary objective of this trial is to evaluate the ef. The paradigmhf trial was a pivotal trial designed to compare the longterm effects of lcz696 with enalapril in patients with symptomatic hf with reduced ejection fraction hfref. Ivabradine and outcomes in chronic heart failure shift. This editorial refers to a randomized controlled study of finerenone vs. We performed a post hoc analysis in all 2737 patients included in the emphasis hf trial. Estimating lifetime benefits of comprehensive disease.
Emphasis hf trial design the design of emphasis hf is published8. Randomized trial to determine the effect of nebivolol on. Estimating the lifetime benefits of treatments for heart failure. This suggests that aldosterone antagonism is beneficial to all patients with symptomatic heart failure with moderatesevere lv systolic dysfunction, and some have speculated that their benefits may extend to those with. Heart failure joann smith, 72 years old primary concept perfusion interrelated concepts in order of emphasis 1. Eplerenone versus placebo renal function stratified dose. The emphasis hf trial which involved 2737 patients from 278 centres with nyha class 2 heart failure and ejection fractions of no more than 35% set out to address the question of whether. Eplerenone in patients with systolic heart failure and mild symptoms. Considering dose in pharmacological therapies for heart. The emphasis hf trial compared eplerenone with placebo added to standard therapy in 2737 patients with new york heart. Study design emphasis hf is a multicentre, randomized, doubleblind, placebocontrolled study.
Heart failure joann smith, 72 years old primary concept perfusion interrelated concepts in order of. Doubleblind, randomized, placebocontrolled trial evaluating. All the authors made the decision to submit the manuscript for publication and assume responsibility for the accuracy and completeness of the data and analyses. Incidence, determinants, and prognostic significance of. Mineralocorticoid receptor antagonist mra therapy improves outcomes in patients with chronic systolic hf with mild symp toms emphasis hf trial, acute. Considering dose in pharmacological therapies for heart failure. Eplerenone versus placebo renal function stratified. A comparison of outcomes in patients in new york heart. Eplerenone is approved for treating heart failure after myocardial infarction in 72 countries. Renal function stratified dose comparisons of eplerenone. Nov 15, 2010 disposition of patients emphasis hf investigators 29 countries, 272 sites 2737 randomized 64 randomized 73 randomized to eplerenone 2550 mg to placebo 4 did not start study drug 4 did not start study drug 17 lost to follow up 15 lost to follow up median followup time 21 months, 4783 patientyears of followup.
Guideline directed medical therapy in heart failure with. 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. Masunori matsuzaki, md, phd for the jemphasishf study group. Since the premature stopping of the trial due to efficacy on may 25th 2010. Results from the emphasis hf trial were used to develop a discreteevent simulation model estimating lifetime direct costs and effects life years and qualityadjusted life years qalys gained of the addition of eplerenone to standard care among patients with chronic systolic hf and mild symptoms. Large heart failure trials with current evidencebased therapies and the percentage of subjects with diabetes in each trial. The design of the emphasishf trial has been published in detail,6 and the trial protocol and.
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