Clinical benefits of eplerenone in patients with systolic heart failure and mild symptoms when initiated shortly after hospital discharge: analysis from the EMPHASIS-HF trial

Girerd, Nicolas; Collier, Timothy J.; Pocock, Stuart J.; Krum, Henry; McMurray, John J.V.; Swedberg, Karl; Veldhuisen, Dirk J. van; Vincent, John; Pitt, Bertram; Zannad, Faı̈ez

doi:10.1093/eurheartj/ehv273

Cited by 31 publications

(20 citation statements)

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“…The information derived from a simple measure of DE can help clinicians in difficult therapeutic decisions, such as escalating diuretics and/or selecting other classes of diuretics (such as mineralocorticoid receptor antagonists [27,28]), in-hospital department allocation (e.g., low monitoring vs. intensive monitoring ward), personalized follow-up, management expectations about disease prognosis, clinical record registries to inform future care providers (e.g., patient required high-intensity diuretic strategy or high-dose spironolactone or ultrafiltration to obtain the fluid loss goal), and it can also provide a potential endpoint for clinical trials [29,30]. …”

Section: Discussionmentioning

confidence: 99%

Lack of Diuretic Efficiency (but Not Low Diuresis) Early in An Acutely Decompensated Heart Failure Episode Is Associated with Increased 180-Day Mortality

Ferreira

Girerd

Ricardo³

et al. 2017

Cardiorenal Med

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Introduction: The assessment of the amount of urine produced by the dose of administered diuretic has been proposed as the main signal of interest in diuretic responsiveness - diuretic efficiency (DE). The main aim of our study is to determine if a low DE is associated with 180-day all-cause mortality (ACM). Methods: During a 3-year period, we retrospectively studied patients with acutely decompensated heart failure (ADHF) and respiratory insufficiency admitted to the emergency room of a tertiary university hospital in Porto, Portugal. A total of 170 patients (age 76.2 ± 10.3 years) were included. The outcome of ACM occurred in 43 (25.3%) patients during the 180-day follow-up period. DE was evaluated for a maximum of 3 h after emergency room admission. The lowest DE was defined as ≤140 mL of diuresis per 40 mg of furosemide equivalents. Results: No significant differences in age, comorbidities, baseline HF symptoms, or disease-modifying medication were found between the lowest and highest DE groups. The lowest DE group had higher blood urea and lower estimated glomerular filtration rate (eGFR) levels (41.3 ± 24.5 vs. 56.7 ± 23.2 mL/min/1.73 m², p < 0.001). The patients with the lowest DE had significantly higher rates of ACM during the 180-day follow-up, even after adjustment for other clinically relevant variables: hazard ratio (HR) [95% CI] = 2.31 [1.16-4.58], p = 0.016. The lowest diuresis (≤300 mL) and the highest intravenous furosemide dose (>80 mg) alone were not significantly associated with the outcome. After adjustment for N-terminal prohormone of brain natriuretic peptide, the association between the lowest DE and the outcome lost strength (HR [95% CI] = 1.53 [0.75-3.13], p = 0.240). Conclusion: A low DE (≤140 mL/40 mg of furosemide) in the first 3 h after an ADHF episode was associated with increased mid-term mortality rates.

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Section: Discussionmentioning

confidence: 99%

Lack of Diuretic Efficiency (but Not Low Diuresis) Early in An Acutely Decompensated Heart Failure Episode Is Associated with Increased 180-Day Mortality

Ferreira

Girerd

Ricardo³

et al. 2017

Cardiorenal Med

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“…A propensity score analysis suggested that discharge use of ACE inhibitor was associated with improvement of prognosis . A recent post‐hoc analysis from the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS‐HF) trial demonstrated that eplerenone prevents readmission when initiated soon after a cardiovascular hospitalization in patients with systolic heart failure and mild symptoms . Only a few randomized clinical trials have explored the effect of treatment during the vulnerable phase after hospitalized heart failure, by analysing outcomes early post‐discharge .…”

Section: Discussionmentioning

confidence: 99%

“…Placebo (n = 672) (EMPHASIS-HF) trial demonstrated that eplerenone prevents readmission when initiated soon after a cardiovascular hospitalization in patients with systolic heart failure and mild symptoms. 15 Only a few randomized clinical trials have explored the effect of treatment during the vulnerable phase after hospitalized heart failure, by analysing outcomes early post-discharge. 16 -20 In a randomized phase II clinical trial, tolvaptan did not demonstrate differences in worsening heart failure at 60 days compared with placebo.…”

Section: Ivabradine (N = 514)mentioning

confidence: 99%

Chronic exposure to ivabradine reduces readmissions in the vulnerable phase after hospitalization for worsening systolic heart failure: a post‐hoc analysis of SHIFT

Komajda

Tavazzi

Swedberg

et al. 2016

European J of Heart Fail

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on behalf of the SHIFT InvestigatorsInternational audienceAims: 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).Methods and results: 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.Conclusion: 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

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“…At 60 days post‐discharge, significantly more patients in the pre‐discharge initiation group were receiving a beta‐blocker (91% vs. 73%, P < 0.0001), and there was a non‐significant trend to a lower incidence of a combined endpoint of death or re‐hospitalization vs. the delayed initiation group (hazard ratio 0.85; 95% confidence interval [CI] 0.56–1.27). An observational, single‐centre study of 685 consecutive patients discharged after admission for AHF suggested that delayed initiation of MRA therapy (30–90 days post‐discharge) is associated with a significant increase in mortality vs. initiation in hospital,16 although a post hoc analysis of the EMPHASIS‐HF study showed that eplerenone prescription shortly after hospital discharge is still beneficial 14…”

Section: Rationale For the Transition Studymentioning

confidence: 99%

“…7 Moreover, as the population ages, the prevalence of HF is expected to increase markedly, with an associated impact on costs. 8,9 Evidence-based therapies in acute heart failure with reduced ejection fraction: impact, timing, and utilization Among patients hospitalized for AHF, administration of evidence-based medications with prognostic impact 10,11 at the time of hospital discharge 12,13 or shortly afterwards 14 has been associated with an improvement in survival and hospital readmission rates. A large observational analysis of outcomes associated with the performance measures recommended by the American College of Cardiology and the American Heart Association found that use of beta-blockers, or an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB), at the time of discharge was associated with significant reductions in mortality and hospital readmission.…”

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confidence: 99%

Rationale and design of TRANSITION: a randomized trial of pre‐discharge vs. post‐discharge initiation of sacubitril/valsartan

et al. 2017

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AimsThe prognosis after hospitalization for acute decompensated heart failure (ADHF) remains poor, especially <30 days post‐discharge. Evidence‐based medications with prognostic impact administered at discharge improve survival and hospital readmission, but robust studies comparing pre‐discharge with post‐discharge initiation are rare. The PARADIGM‐HF trial established sacubitril/valsartan as a new evidence‐based therapy in patients with heart failure (HF) and reduced left ventricular ejection fraction (<40%) (rEF). In common with other landmark studies, it enrolled patients who were ambulatory at the time of inclusion. In addition, there is also still limited knowledge of initiation and up‐titration of sacubitril/valsartan in ACEi/ARB‐ naïve patients and in de novo HF with rEF patients.Methods and results TRANSITION is a multicentre, open‐label study in which ~1000 adults hospitalized for ADHF with rEF are randomized to start sacubitril/valsartan in a pre‐discharge arm (initiated ≥24 h after haemodynamic stabilization) or a post‐discharge arm (initiated within Days 1–14 after discharge). The protocol allows investigators to select the appropriate starting dose and dose adjustments according to clinical circumstances. Over a 10 week treatment period, the primary and secondary objectives assess the feasibility and safety of starting sacubitril/valsartan in‐hospital, early after haemodynamic stabilization. Exploratory objectives also include assessment of HF signs and symptoms, readmissions, N‐terminal pro‐B‐type natriuretic peptide and high‐sensitivity troponin T levels, and health resource utilization parameters.Conclusions TRANSITION will provide new evidence about initiating sacubitril/valsartan following hospitalization for ADHF, occurring either as de novo ADHF or as deterioration of chronic HF, and in patients with or without prior ACEI/ARB therapy. The results of TRANSITION will thus be highly relevant to the management of patients hospitalized for ADHF with rEF.

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Clinical benefits of eplerenone in patients with systolic heart failure and mild symptoms when initiated shortly after hospital discharge: analysis from the EMPHASIS-HF trial

Abstract: 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.

Cited by 31 publications

References 32 publications

Lack of Diuretic Efficiency (but Not Low Diuresis) Early in An Acutely Decompensated Heart Failure Episode Is Associated with Increased 180-Day Mortality

Lack of Diuretic Efficiency (but Not Low Diuresis) Early in An Acutely Decompensated Heart Failure Episode Is Associated with Increased 180-Day Mortality

Chronic exposure to ivabradine reduces readmissions in the vulnerable phase after hospitalization for worsening systolic heart failure: a post‐hoc analysis of SHIFT

Rationale and design of TRANSITION: a randomized trial of pre‐discharge vs. post‐discharge initiation of sacubitril/valsartan

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