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Faiez Zannad - One of the best experts on this subject based on the ideXlab platform.

  • serum sodium and Eplerenone use in patients with a myocardial infarction and left ventricular dysfunction or heart failure insights from the ephesus trial
    Clinical Research in Cardiology, 2021
    Co-Authors: Pieter Martens, Joao Pedro Ferreira, Paula Abreu, John Vincent, Bertram Pitt, Martijn Busselen, Wilfried Mullens, Wilson W H Tang, Michael Bohm, Faiez Zannad
    Abstract:

    Sodium changes are common in myocardial infarction (MI) complicated with left ventricular systolic dysfunction (LVSD) and/or heart failure (HF). Sodium handling is fine-tuned in the distal nephron, were Eplerenone exhibits some of its pleotropic effects. Little is known about the effect of Eplerenone on serum sodium and the prognostic relevance of sodium alterations in patients with MI complicated with LVSD and/or HF. The EPHESUS trial randomized 6632 patients to either Eplerenone or placebo. Hyponatremia and hypernatremia were defined as sodium   145 mmol/L, respectively. Linear mixed models and time updated Cox regression analysis were used to determine the effect of Eplerenone on sodium changes and the prognostic importance of sodium changes, respectively. The primary outcomes were all-cause mortality and a composite of cardiovascular (CV) mortality and CV-hospitalization. A total of 6221 patients had a post-baseline sodium measurement, 797 patients developed hyponatremia (mean of 0.2 events/per patient) and 1476 developed hypernatremia (mean of 0.4 events/per patient). Patients assigned to Eplerenone had a lower mean serum sodium over the follow-up (140 vs 141 mmol/L; p   0.05 for all). Development of new-onset hyponatremia following Eplerenone initiation did not diminish the beneficial Eplerenone treatment effect. Eplerenone induces minor reductions in serum sodium. The beneficial effect of Eplerenone was maintained regardless of the baseline serum sodium or the development of hyponatremia. Sodium alterations should not refrain clinicians from prescribing Eplerenone to patients who had an MI complicated with LVSD and/or HF. ClinicalTrials.gov identifier: NCT00232180. Serum sodium and Eplerenone use in patients with a myocardial infarction and left ventricular dysfunction or heart failure: insights from the EPHESUS trial.

  • Serum microRNAs and antifibrotic response to Eplerenone in acute myocardial infarction complicated by systolic dysfunction
    International Journal of Cardiology, 2021
    Co-Authors: Susan Stienen, Joao Pedro Ferreira, Patrick Rossignol, Bertram Pitt, Nicolas Girerd, Christian Bär, Thomas Thum, António Barros, Faiez Zannad
    Abstract:

    Background After myocardial infarction (MI) complicated by heart failure (HF), Eplerenone reduced serum concentrations of amino-terminal propeptide of type III collagen (PIIINP) and carboxy-terminal propeptide of type I collagen (PICP). Determining a subgroup who are more prone to decrease their collagen content and to respond better to the antifibrotic effects of mineralocorticoid receptor antagonists (MRA) may be relevant for a personalized treatment approach. Whether circulating microRNAs may identify a subgroup that have experienced a more pronounced antifibrotic effect of Eplerenone as measured by a PICP and PIIINP decrease is unclear. Methods A set of circulating microRNAs linked to cardiac fibrosis (mir-1, mir-21, mir-29a, mir-29b, mir-101, mir-122, mir-133a) were measured at baseline in 198 patients in the biomarker substudy of Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS). Associations between baseline microRNA levels and changes in both PIIINP and PICP from baseline to month 9 were studied using multivariable analysis of covariance, adjusting for age, sex, history of hypertension and diabetes mellitus, prescription of ACE-inhibitors or angiotensin receptor blockers, baseline PIIINP or PICP, and Eplerenone treatment. Furthermore, a treatment-by-microRNA interaction was studied. Results From the selected microRNAs, only mir-133a was associated with a PICP decrease (ß-6.43, 95%CI-12.71 to −0.15,p = 0.045). None of the microRNAs was associated with a PIIINP change. The microRNAs did not predict an effect of Eplerenone on PICP and PIIINP changes. Conclusion Although serum mir-133a was associated with PICP change, none of the microRNAs previously linked to cardiac fibrosis predicted an antifibrotic response to Eplerenone. Further study is needed to identify other suitable targets for a personalized treatment approach.

  • determinants of anti fibrotic response to mineralocorticoid receptor antagonist therapy insights from the Eplerenone post acute myocardial infarction heart failure efficacy and survival study ephesus and early Eplerenone treatment in patients with acute st elevation myocardial infarction without heart failure reminder trials
    Clinical Research in Cardiology, 2020
    Co-Authors: Susan Stienen, Joao Pedro Ferreira, Patrick Rossignol, Bertram Pitt, Faiez Zannad, Nicolas Girerd, Antonio S Barros
    Abstract:

    After myocardial infarction complicated by heart failure or diabetes, Eplerenone (compared to placebo) significantly decreases amino-terminal propeptide of type III procollagen (PIIINP). Determining the subset of patients who are more prone to have a decrease in PIIINP and those who may respond better to the anti-fibrotic effects of mineralocorticoid receptor antagonists (MRA) therapy may be relevant for a personalized treatment approach. The aim of this study is to identify predictors of a PIIINP decrease and assess potential subgroups of “responders” to Eplerenone. Clinical factors and biomarkers were evaluated as predictors of a PIIINP decrease from randomization to month 9 in 323 patients from the biomarker substudy of Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS). Additionally, the association between PIIINP decrease and the composite of cardiovascular (CV) death or CV hospitalization were also explored. External validation was performed in the REMINDER trial. Female sex, Eplerenone, reperfusion therapy, potassium < 4 mmol/L, circulating levels of PIIINP ≥ 3.6 ng/mL and PINP ≥ 27 ng/mL predicted a PIIINP decrease (AUC = 0.75). Randomization PIIINP showed a significant interaction with the treatment allocation: patients with PIIINP ≥ 3.6 ng/mL had a better response (decrease in PIIINP) to Eplerenone (OR for PIIINP ≥ 3.6 = 2.9, 95% CI 1.46–5.89, p = 0.003) and OR for PIIINP < 3.6 = 1.09, 95% CI 0.55–2.2, p = 0.8; interactionp = 0.026). These findings were internally robust using another statistical approach (LOESS). External validation showed good discrimination (AUC = 0.70). There was a tendency toward a lower rate of CV death/CV hospitalizations in patients with decreased PIIINP (adjusted HR = 0.52, 95% CI 0.26–1.02, p = 0.058). In patients who had a myocardial infarction, clinical factors used in combination and treatment with Eplerenone were associated with a PIIINP decrease. Interestingly, higher randomization PIIINP levels might help in identifying patients more prone to have an “anti-fibrotic response” when treated with MRAs. Predictors of an antifibrotic response after MI complicated by HF. Several clinical factors and biomarkers predicted a PIIINP decrease after an MI complicated by HF. There was a significant interaction between baseline PIIINP levels and Eplerenone treatment: patients with baseline PIIINP ≥ 3.6 mmol/L treated with Eplerenone had the best response (PIIINP decrease).

  • impact of Eplerenone on major cardiovascular outcomes in patients with systolic heart failure according to baseline heart rate
    Clinical Research in Cardiology, 2019
    Co-Authors: Ken Lee Chin, John J V Mcmurray, Dirk J Van Veldhuisen, Karl Swedberg, Stuart J Pocock, John Vincent, Bertram Pitt, T Collier, Faiez Zannad
    Abstract:

    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.

  • abstract 16638 effect of Eplerenone according to qrs duration and morphology in emphasis hf
    Circulation, 2014
    Co-Authors: Jane A Cannon, Dirk J Van Veldhuisen, Karl Swedberg, Stuart J Pocock, John Vincent, Bertram Pitt, Faiez Zannad, Henry Krum, T Collier, John J V Mcmurray
    Abstract:

    Background: The importance of QRS duration (QRSd) and QRS morphology (left and right bundle-branch block [LBBB, RBBB], interventricular conduction defect [IVCD]) as predictors of prognosis and value in selecting patients for device therapy is increasingly recognized. We examined the effect of Eplerenone in heart failure with reduced ejection fraction (HF-REF), according to QRSd/morphology in EMPHASIS-HF. Methods: Patients were categorized as: QRSd (msec) a) <120 (n=1375), b) 120-149 (n=517) and c) 150+ (n=383) and QRS morphology i) normal (n=1252), ii) RBBB/IVCD (n=415) and iii) LBBB (n=608); 462 patients were excluded because of missing or incorrect ECG data. Occurrence of the primary composite outcome of cardiovascular death or heart failure hospitalization was estimated in patients randomized to placebo or Eplerenone. The effect of Eplerenone was adjusted for the previously described predictors of the primary outcome in EMPHASIS-HF. Results: Both prolonged QRSd and abnormal QRS morphology were associated with increased risk. Eplerenone reduced the risk of the primary outcome, compared with placebo, in all patients (n=2275) with ECG data (HR 0.71, 95% CI 0.60-0.84 p<0.001) and this beneficial effect was consistent across QRSd and QRS morphology subgroups (Table). Conclusion: We confirmed the association between QRS prolongation and adverse outcomes in HF-REF. Eplerenone was similarly effective, irrespective of QRSd and morphology. ![][1] [1]: /embed/graphic-1.gif

Bertram Pitt - One of the best experts on this subject based on the ideXlab platform.

  • serum sodium and Eplerenone use in patients with a myocardial infarction and left ventricular dysfunction or heart failure insights from the ephesus trial
    Clinical Research in Cardiology, 2021
    Co-Authors: Pieter Martens, Joao Pedro Ferreira, Paula Abreu, John Vincent, Bertram Pitt, Martijn Busselen, Wilfried Mullens, Wilson W H Tang, Michael Bohm, Faiez Zannad
    Abstract:

    Sodium changes are common in myocardial infarction (MI) complicated with left ventricular systolic dysfunction (LVSD) and/or heart failure (HF). Sodium handling is fine-tuned in the distal nephron, were Eplerenone exhibits some of its pleotropic effects. Little is known about the effect of Eplerenone on serum sodium and the prognostic relevance of sodium alterations in patients with MI complicated with LVSD and/or HF. The EPHESUS trial randomized 6632 patients to either Eplerenone or placebo. Hyponatremia and hypernatremia were defined as sodium   145 mmol/L, respectively. Linear mixed models and time updated Cox regression analysis were used to determine the effect of Eplerenone on sodium changes and the prognostic importance of sodium changes, respectively. The primary outcomes were all-cause mortality and a composite of cardiovascular (CV) mortality and CV-hospitalization. A total of 6221 patients had a post-baseline sodium measurement, 797 patients developed hyponatremia (mean of 0.2 events/per patient) and 1476 developed hypernatremia (mean of 0.4 events/per patient). Patients assigned to Eplerenone had a lower mean serum sodium over the follow-up (140 vs 141 mmol/L; p   0.05 for all). Development of new-onset hyponatremia following Eplerenone initiation did not diminish the beneficial Eplerenone treatment effect. Eplerenone induces minor reductions in serum sodium. The beneficial effect of Eplerenone was maintained regardless of the baseline serum sodium or the development of hyponatremia. Sodium alterations should not refrain clinicians from prescribing Eplerenone to patients who had an MI complicated with LVSD and/or HF. ClinicalTrials.gov identifier: NCT00232180. Serum sodium and Eplerenone use in patients with a myocardial infarction and left ventricular dysfunction or heart failure: insights from the EPHESUS trial.

  • Serum microRNAs and antifibrotic response to Eplerenone in acute myocardial infarction complicated by systolic dysfunction
    International Journal of Cardiology, 2021
    Co-Authors: Susan Stienen, Joao Pedro Ferreira, Patrick Rossignol, Bertram Pitt, Nicolas Girerd, Christian Bär, Thomas Thum, António Barros, Faiez Zannad
    Abstract:

    Background After myocardial infarction (MI) complicated by heart failure (HF), Eplerenone reduced serum concentrations of amino-terminal propeptide of type III collagen (PIIINP) and carboxy-terminal propeptide of type I collagen (PICP). Determining a subgroup who are more prone to decrease their collagen content and to respond better to the antifibrotic effects of mineralocorticoid receptor antagonists (MRA) may be relevant for a personalized treatment approach. Whether circulating microRNAs may identify a subgroup that have experienced a more pronounced antifibrotic effect of Eplerenone as measured by a PICP and PIIINP decrease is unclear. Methods A set of circulating microRNAs linked to cardiac fibrosis (mir-1, mir-21, mir-29a, mir-29b, mir-101, mir-122, mir-133a) were measured at baseline in 198 patients in the biomarker substudy of Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS). Associations between baseline microRNA levels and changes in both PIIINP and PICP from baseline to month 9 were studied using multivariable analysis of covariance, adjusting for age, sex, history of hypertension and diabetes mellitus, prescription of ACE-inhibitors or angiotensin receptor blockers, baseline PIIINP or PICP, and Eplerenone treatment. Furthermore, a treatment-by-microRNA interaction was studied. Results From the selected microRNAs, only mir-133a was associated with a PICP decrease (ß-6.43, 95%CI-12.71 to −0.15,p = 0.045). None of the microRNAs was associated with a PIIINP change. The microRNAs did not predict an effect of Eplerenone on PICP and PIIINP changes. Conclusion Although serum mir-133a was associated with PICP change, none of the microRNAs previously linked to cardiac fibrosis predicted an antifibrotic response to Eplerenone. Further study is needed to identify other suitable targets for a personalized treatment approach.

  • determinants of anti fibrotic response to mineralocorticoid receptor antagonist therapy insights from the Eplerenone post acute myocardial infarction heart failure efficacy and survival study ephesus and early Eplerenone treatment in patients with acute st elevation myocardial infarction without heart failure reminder trials
    Clinical Research in Cardiology, 2020
    Co-Authors: Susan Stienen, Joao Pedro Ferreira, Patrick Rossignol, Bertram Pitt, Faiez Zannad, Nicolas Girerd, Antonio S Barros
    Abstract:

    After myocardial infarction complicated by heart failure or diabetes, Eplerenone (compared to placebo) significantly decreases amino-terminal propeptide of type III procollagen (PIIINP). Determining the subset of patients who are more prone to have a decrease in PIIINP and those who may respond better to the anti-fibrotic effects of mineralocorticoid receptor antagonists (MRA) therapy may be relevant for a personalized treatment approach. The aim of this study is to identify predictors of a PIIINP decrease and assess potential subgroups of “responders” to Eplerenone. Clinical factors and biomarkers were evaluated as predictors of a PIIINP decrease from randomization to month 9 in 323 patients from the biomarker substudy of Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS). Additionally, the association between PIIINP decrease and the composite of cardiovascular (CV) death or CV hospitalization were also explored. External validation was performed in the REMINDER trial. Female sex, Eplerenone, reperfusion therapy, potassium < 4 mmol/L, circulating levels of PIIINP ≥ 3.6 ng/mL and PINP ≥ 27 ng/mL predicted a PIIINP decrease (AUC = 0.75). Randomization PIIINP showed a significant interaction with the treatment allocation: patients with PIIINP ≥ 3.6 ng/mL had a better response (decrease in PIIINP) to Eplerenone (OR for PIIINP ≥ 3.6 = 2.9, 95% CI 1.46–5.89, p = 0.003) and OR for PIIINP < 3.6 = 1.09, 95% CI 0.55–2.2, p = 0.8; interactionp = 0.026). These findings were internally robust using another statistical approach (LOESS). External validation showed good discrimination (AUC = 0.70). There was a tendency toward a lower rate of CV death/CV hospitalizations in patients with decreased PIIINP (adjusted HR = 0.52, 95% CI 0.26–1.02, p = 0.058). In patients who had a myocardial infarction, clinical factors used in combination and treatment with Eplerenone were associated with a PIIINP decrease. Interestingly, higher randomization PIIINP levels might help in identifying patients more prone to have an “anti-fibrotic response” when treated with MRAs. Predictors of an antifibrotic response after MI complicated by HF. Several clinical factors and biomarkers predicted a PIIINP decrease after an MI complicated by HF. There was a significant interaction between baseline PIIINP levels and Eplerenone treatment: patients with baseline PIIINP ≥ 3.6 mmol/L treated with Eplerenone had the best response (PIIINP decrease).

  • impact of Eplerenone on major cardiovascular outcomes in patients with systolic heart failure according to baseline heart rate
    Clinical Research in Cardiology, 2019
    Co-Authors: Ken Lee Chin, John J V Mcmurray, Dirk J Van Veldhuisen, Karl Swedberg, Stuart J Pocock, John Vincent, Bertram Pitt, T Collier, Faiez Zannad
    Abstract:

    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.

  • effect of Eplerenone on extracellular cardiac matrix biomarkers in patients with acute st elevation myocardial infarction without heart failure insights from the randomized double blind reminder study
    Clinical Research in Cardiology, 2018
    Co-Authors: Harry Shi, Joao Pedro Ferreira, Bertram Pitt, Kevin Duarte, Gilles Montalescot, Christian W Hamm, Marcus Flather, Freek W A Verheugt, Eva Turgonyi
    Abstract:

    Aldosterone stimulates cardiac collagen synthesis. Circulating biomarkers of collagen turnover provide a useful tool for the assessment of cardiac remodeling in patients with an acute myocardial infarction (MI). The REMINDER trial assessed the effect of Eplerenone in patients with an acute ST-elevation Myocardial Infarction (STEMI) without known heart failure (HF), when initiated within 24 h of symptom onset. The primary outcome was almost totally (>90%) driven by natriuretic peptide (NP) thresholds after 1-month post-MI (it also included a composite of cardiovascular death or re-hospitalization or new onset HF or sustained ventricular tachycardia or fibrillation or LVEF ≤40% after 1-month post-MI). This secondary analysis aims to assess the extracellular matrix marker (ECMM) levels with regards to: (1) patients` characteristics; (2) determinants; (3) and Eplerenone effect. Serum levels of ECMM were measured in 526 (52%) of the 1012 patients enrolled in the REMINDER trial. Patients with procollagen type III N-terminal propeptide (PIIINP) above the median were older and had worse renal function (p < 0.05). Worse renal function was associated with increased levels of PIIINP (standardized β ≈ 0.20, p < 0.05). Eplerenone reduced PIIINP when the levels of this biomarker were above the median of 3.9 ng/mL (0.13 ± 1.48 vs. −0.37 ± 1.56 ng/mL, p = 0.008). Higher levels of PIIINP were independently associated with higher proportion of NP above the prespecified thresholds (HR = 1.95, 95% CI 1.16–3.29, p = 0.012). Eplerenone effectively reduces PIIINP levels when baseline values were above the median. Eplerenone may limit ECMM formation in post-MI without HF.

Henry Krum - One of the best experts on this subject based on the ideXlab platform.

  • impact of Eplerenone on cardiovascular outcomes in heart failure patients with hypokalaemia
    European Journal of Heart Failure, 2017
    Co-Authors: Patrick Rossignol, John J V Mcmurray, Dirk J Van Veldhuisen, Karl Swedberg, Henry Krum, Nicolas Girerd, George L Bakris, Orly Vardeny, Brian Claggett, Harry Shi
    Abstract:

    Aims 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. Methods and results Results of the EMPHASIS-HF trial in patients (n = 2737) with HF and reduced EF with mild symptoms, randomized to Eplerenone or placebo, were analysed with regard to the presence or occurrence of hypokalaemia (serum K+ 4.0 mmol/L at 1 month after randomization mediated 26.0% (0.6–51.4%) of the Eplerenone treatment effect (P = 0.04). Conclusion 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.

  • abstract 16638 effect of Eplerenone according to qrs duration and morphology in emphasis hf
    Circulation, 2014
    Co-Authors: Jane A Cannon, Dirk J Van Veldhuisen, Karl Swedberg, Stuart J Pocock, John Vincent, Bertram Pitt, Faiez Zannad, Henry Krum, T Collier, John J V Mcmurray
    Abstract:

    Background: The importance of QRS duration (QRSd) and QRS morphology (left and right bundle-branch block [LBBB, RBBB], interventricular conduction defect [IVCD]) as predictors of prognosis and value in selecting patients for device therapy is increasingly recognized. We examined the effect of Eplerenone in heart failure with reduced ejection fraction (HF-REF), according to QRSd/morphology in EMPHASIS-HF. Methods: Patients were categorized as: QRSd (msec) a) <120 (n=1375), b) 120-149 (n=517) and c) 150+ (n=383) and QRS morphology i) normal (n=1252), ii) RBBB/IVCD (n=415) and iii) LBBB (n=608); 462 patients were excluded because of missing or incorrect ECG data. Occurrence of the primary composite outcome of cardiovascular death or heart failure hospitalization was estimated in patients randomized to placebo or Eplerenone. The effect of Eplerenone was adjusted for the previously described predictors of the primary outcome in EMPHASIS-HF. Results: Both prolonged QRSd and abnormal QRS morphology were associated with increased risk. Eplerenone reduced the risk of the primary outcome, compared with placebo, in all patients (n=2275) with ECG data (HR 0.71, 95% CI 0.60-0.84 p<0.001) and this beneficial effect was consistent across QRSd and QRS morphology subgroups (Table). Conclusion: We confirmed the association between QRS prolongation and adverse outcomes in HF-REF. Eplerenone was similarly effective, irrespective of QRSd and morphology. ![][1] [1]: /embed/graphic-1.gif

  • cost effectiveness of Eplerenone in patients with systolic heart failure and mild symptoms
    Heart, 2014
    Co-Authors: Dawn Lee, Dirk J Van Veldhuisen, John Vincent, Bertram Pitt, Faiez Zannad, Henry Krum, Koo Wilson, Ron Akehurst, Martin R Cowie, John J V Mcmurray
    Abstract:

    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. 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). 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.

  • the impact of Eplerenone at different levels of risk in patients with systolic heart failure and mild symptoms insight from a novel risk score for prognosis derived from the emphasis hf trial
    European Heart Journal, 2013
    Co-Authors: T Collier, Harry Shi, John J V Mcmurray, Dirk J Van Veldhuisen, Karl Swedberg, Stuart J Pocock, Faiez Zannad, Henry Krum, John Vincent
    Abstract:

    Aims 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. Methods and results 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. Conclusion 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.

  • Eplerenone in patients with systolic heart failure and mild symptoms analysis of repeat hospitalizations
    Circulation, 2012
    Co-Authors: Jennifer K Rogers, Harry Shi, John J V Mcmurray, Dirk J Van Veldhuisen, Karl Swedberg, Stuart J Pocock, John Vincent, Faiez Zannad, Henry Krum, Bertram Pitt
    Abstract:

    BACKGROUND: 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. METHODS AND RESULTS: 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. CONCLUSIONS: 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. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00232180.

Patrick Rossignol - One of the best experts on this subject based on the ideXlab platform.

  • Serum microRNAs and antifibrotic response to Eplerenone in acute myocardial infarction complicated by systolic dysfunction
    International Journal of Cardiology, 2021
    Co-Authors: Susan Stienen, Joao Pedro Ferreira, Patrick Rossignol, Bertram Pitt, Nicolas Girerd, Christian Bär, Thomas Thum, António Barros, Faiez Zannad
    Abstract:

    Background After myocardial infarction (MI) complicated by heart failure (HF), Eplerenone reduced serum concentrations of amino-terminal propeptide of type III collagen (PIIINP) and carboxy-terminal propeptide of type I collagen (PICP). Determining a subgroup who are more prone to decrease their collagen content and to respond better to the antifibrotic effects of mineralocorticoid receptor antagonists (MRA) may be relevant for a personalized treatment approach. Whether circulating microRNAs may identify a subgroup that have experienced a more pronounced antifibrotic effect of Eplerenone as measured by a PICP and PIIINP decrease is unclear. Methods A set of circulating microRNAs linked to cardiac fibrosis (mir-1, mir-21, mir-29a, mir-29b, mir-101, mir-122, mir-133a) were measured at baseline in 198 patients in the biomarker substudy of Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS). Associations between baseline microRNA levels and changes in both PIIINP and PICP from baseline to month 9 were studied using multivariable analysis of covariance, adjusting for age, sex, history of hypertension and diabetes mellitus, prescription of ACE-inhibitors or angiotensin receptor blockers, baseline PIIINP or PICP, and Eplerenone treatment. Furthermore, a treatment-by-microRNA interaction was studied. Results From the selected microRNAs, only mir-133a was associated with a PICP decrease (ß-6.43, 95%CI-12.71 to −0.15,p = 0.045). None of the microRNAs was associated with a PIIINP change. The microRNAs did not predict an effect of Eplerenone on PICP and PIIINP changes. Conclusion Although serum mir-133a was associated with PICP change, none of the microRNAs previously linked to cardiac fibrosis predicted an antifibrotic response to Eplerenone. Further study is needed to identify other suitable targets for a personalized treatment approach.

  • determinants of anti fibrotic response to mineralocorticoid receptor antagonist therapy insights from the Eplerenone post acute myocardial infarction heart failure efficacy and survival study ephesus and early Eplerenone treatment in patients with acute st elevation myocardial infarction without heart failure reminder trials
    Clinical Research in Cardiology, 2020
    Co-Authors: Susan Stienen, Joao Pedro Ferreira, Patrick Rossignol, Bertram Pitt, Faiez Zannad, Nicolas Girerd, Antonio S Barros
    Abstract:

    After myocardial infarction complicated by heart failure or diabetes, Eplerenone (compared to placebo) significantly decreases amino-terminal propeptide of type III procollagen (PIIINP). Determining the subset of patients who are more prone to have a decrease in PIIINP and those who may respond better to the anti-fibrotic effects of mineralocorticoid receptor antagonists (MRA) therapy may be relevant for a personalized treatment approach. The aim of this study is to identify predictors of a PIIINP decrease and assess potential subgroups of “responders” to Eplerenone. Clinical factors and biomarkers were evaluated as predictors of a PIIINP decrease from randomization to month 9 in 323 patients from the biomarker substudy of Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS). Additionally, the association between PIIINP decrease and the composite of cardiovascular (CV) death or CV hospitalization were also explored. External validation was performed in the REMINDER trial. Female sex, Eplerenone, reperfusion therapy, potassium < 4 mmol/L, circulating levels of PIIINP ≥ 3.6 ng/mL and PINP ≥ 27 ng/mL predicted a PIIINP decrease (AUC = 0.75). Randomization PIIINP showed a significant interaction with the treatment allocation: patients with PIIINP ≥ 3.6 ng/mL had a better response (decrease in PIIINP) to Eplerenone (OR for PIIINP ≥ 3.6 = 2.9, 95% CI 1.46–5.89, p = 0.003) and OR for PIIINP < 3.6 = 1.09, 95% CI 0.55–2.2, p = 0.8; interactionp = 0.026). These findings were internally robust using another statistical approach (LOESS). External validation showed good discrimination (AUC = 0.70). There was a tendency toward a lower rate of CV death/CV hospitalizations in patients with decreased PIIINP (adjusted HR = 0.52, 95% CI 0.26–1.02, p = 0.058). In patients who had a myocardial infarction, clinical factors used in combination and treatment with Eplerenone were associated with a PIIINP decrease. Interestingly, higher randomization PIIINP levels might help in identifying patients more prone to have an “anti-fibrotic response” when treated with MRAs. Predictors of an antifibrotic response after MI complicated by HF. Several clinical factors and biomarkers predicted a PIIINP decrease after an MI complicated by HF. There was a significant interaction between baseline PIIINP levels and Eplerenone treatment: patients with baseline PIIINP ≥ 3.6 mmol/L treated with Eplerenone had the best response (PIIINP decrease).

  • effect of the mineralocorticoid receptor antagonist Eplerenone on liver fat and metabolism in patients with type 2 diabetes a randomized double blind placebo controlled trial mirad trial
    Diabetes Obesity and Metabolism, 2019
    Co-Authors: Patrick Rossignol, Marie Louise Johansen, Morten Schou, Maria Refsgaard Holm, Jon Rasmussen, Niels Jacob Brandt, Mikkel N Frandsen
    Abstract:

    AIM To investigate whether the mineralocorticoid receptor antagonist Eplerenone has beneficial effects on liver fat and metabolism in patients with type 2 diabetes (T2D), the mineralocorticoid receptor antagonist in type 2 diabetes (MIRAD) trial. MATERIAL AND METHODS In this 26-week, double-blind, randomized, placebo-controlled trial, we enrolled 140 patients with T2D and high risk of cardiovascular disease. Patients were randomized 1:1 to either Eplerenone with a target dose of 200 mg/day for patients with estimated glomerular filtration rate (eGFR) of 60 mL/min per 1.73 m2 or more and 100 mg/day for patients with eGFR between 41 and 59 mL/min per 1.73 m2 or placebo. The primary outcome measure was change in liver fat by proton magnetic resonance spectroscopy at week 26 from baseline; secondary outcomes were changes in metabolism, and safety by incident hyperkalaemia. RESULTS No changes in liver fat in the Eplerenone group 0.91% (95% CI -0.57 to 2.39) or the placebo group -1.01% (-2.23 to 0.21) were found. The estimated absolute treatment difference was 1.92% (-3.81 to 0.01; P = 0.049). There was no beneficial impact on supporting secondary outcome variables of metabolism as fat mass distribution, lipid metabolism or insulin resistance. Despite a high dosage of Eplerenone 164 versus 175 mg in patients treated with placebo (P = 0.228), the number of patients with incident hyperkalaemia (≥5.5 mmol/L) was low, with six in the Eplerenone versus two in the placebo group (P = 0.276). CONCLUSION The addition of high doses of Eplerenone to background antidiabetic and antihypertensive therapy does not show beneficial effects on liver fat and metabolism in patients with T2D.

  • renal function stratified dose comparisons of Eplerenone versus placebo in the emphasis hf trial
    European Journal of Heart Failure, 2019
    Co-Authors: Joao Pedro Ferreira, Paula Abreu, John J V Mcmurray, Dirk J Van Veldhuisen, Karl Swedberg, Stuart J Pocock, John Vincent, Katharina Lins, Patrick Rossignol
    Abstract:

    Background: Current heart failure guidelines recommend target Eplerenone dose of 50 mg/day. We have examined the effect of different Eplerenone doses based on pre‐specified renal function stratification in the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS‐HF). Methods and results: In EMPHASIS‐HF, the target dose of Eplerenone/placebo was stratified at randomization according to estimated glomerular filtration rate (eGFR): 50 mg/day if eGFR ≥ 50 mL/min/1.73 m2 and ≤ 25 mg/day if eGFR 30–49 mL/min/1.73 m2. Patients remained within these dose ranges during the trial (as per stratification). The primary outcome was a composite of heart failure hospitalization or cardiovascular mortality. Eplerenone was superior to placebo within each respective eGFR stratum [Eplerenone vs. placebo in the eGFR ≥ 50 mL/min/1.73 m2 stratum: hazard ratio (HR) 0.58, 95% confidence interval (CI) 0.45–0.74; and Eplerenone vs. placebo in the eGFR 30–49 mL/min/1.73 m2 stratum: HR 0.62, 95% CI 0.49–0.78; Pinteraction = 0.89]. Despite receiving lower Eplerenone doses, patients in the eGFR 30–49 mL/min/1.73 m2 stratum more often had hyperkalaemia, renal failure events, and drug discontinuation. Conclusion: In EMPHASIS‐HF the Eplerenone dose was stratified according to renal function and the treatment effect was not influenced by renal function: 25 mg/day in patients with eGFR 30–49 mL/min/1.73 m2 was as effective as 50 mg/day in patients with eGFR > =50 mL/min/1.73 m2. However, patients with impaired renal function experienced more adverse events, despite reveiving lower Eplerenone doses. Current guidelines do not recommend tailoring the dose of eplereone according to renal function but the current data suggest they should.

  • impact of Eplerenone on cardiovascular outcomes in heart failure patients with hypokalaemia
    European Journal of Heart Failure, 2017
    Co-Authors: Patrick Rossignol, John J V Mcmurray, Dirk J Van Veldhuisen, Karl Swedberg, Henry Krum, Nicolas Girerd, George L Bakris, Orly Vardeny, Brian Claggett, Harry Shi
    Abstract:

    Aims 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. Methods and results Results of the EMPHASIS-HF trial in patients (n = 2737) with HF and reduced EF with mild symptoms, randomized to Eplerenone or placebo, were analysed with regard to the presence or occurrence of hypokalaemia (serum K+ 4.0 mmol/L at 1 month after randomization mediated 26.0% (0.6–51.4%) of the Eplerenone treatment effect (P = 0.04). Conclusion 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.

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  • serum sodium and Eplerenone use in patients with a myocardial infarction and left ventricular dysfunction or heart failure insights from the ephesus trial
    Clinical Research in Cardiology, 2021
    Co-Authors: Pieter Martens, Joao Pedro Ferreira, Paula Abreu, John Vincent, Bertram Pitt, Martijn Busselen, Wilfried Mullens, Wilson W H Tang, Michael Bohm, Faiez Zannad
    Abstract:

    Sodium changes are common in myocardial infarction (MI) complicated with left ventricular systolic dysfunction (LVSD) and/or heart failure (HF). Sodium handling is fine-tuned in the distal nephron, were Eplerenone exhibits some of its pleotropic effects. Little is known about the effect of Eplerenone on serum sodium and the prognostic relevance of sodium alterations in patients with MI complicated with LVSD and/or HF. The EPHESUS trial randomized 6632 patients to either Eplerenone or placebo. Hyponatremia and hypernatremia were defined as sodium   145 mmol/L, respectively. Linear mixed models and time updated Cox regression analysis were used to determine the effect of Eplerenone on sodium changes and the prognostic importance of sodium changes, respectively. The primary outcomes were all-cause mortality and a composite of cardiovascular (CV) mortality and CV-hospitalization. A total of 6221 patients had a post-baseline sodium measurement, 797 patients developed hyponatremia (mean of 0.2 events/per patient) and 1476 developed hypernatremia (mean of 0.4 events/per patient). Patients assigned to Eplerenone had a lower mean serum sodium over the follow-up (140 vs 141 mmol/L; p   0.05 for all). Development of new-onset hyponatremia following Eplerenone initiation did not diminish the beneficial Eplerenone treatment effect. Eplerenone induces minor reductions in serum sodium. The beneficial effect of Eplerenone was maintained regardless of the baseline serum sodium or the development of hyponatremia. Sodium alterations should not refrain clinicians from prescribing Eplerenone to patients who had an MI complicated with LVSD and/or HF. ClinicalTrials.gov identifier: NCT00232180. Serum sodium and Eplerenone use in patients with a myocardial infarction and left ventricular dysfunction or heart failure: insights from the EPHESUS trial.

  • renal function stratified dose comparisons of Eplerenone versus placebo in the emphasis hf trial
    European Journal of Heart Failure, 2019
    Co-Authors: Joao Pedro Ferreira, Paula Abreu, John J V Mcmurray, Dirk J Van Veldhuisen, Karl Swedberg, Stuart J Pocock, John Vincent, Katharina Lins, Patrick Rossignol
    Abstract:

    Background: Current heart failure guidelines recommend target Eplerenone dose of 50 mg/day. We have examined the effect of different Eplerenone doses based on pre‐specified renal function stratification in the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS‐HF). Methods and results: In EMPHASIS‐HF, the target dose of Eplerenone/placebo was stratified at randomization according to estimated glomerular filtration rate (eGFR): 50 mg/day if eGFR ≥ 50 mL/min/1.73 m2 and ≤ 25 mg/day if eGFR 30–49 mL/min/1.73 m2. Patients remained within these dose ranges during the trial (as per stratification). The primary outcome was a composite of heart failure hospitalization or cardiovascular mortality. Eplerenone was superior to placebo within each respective eGFR stratum [Eplerenone vs. placebo in the eGFR ≥ 50 mL/min/1.73 m2 stratum: hazard ratio (HR) 0.58, 95% confidence interval (CI) 0.45–0.74; and Eplerenone vs. placebo in the eGFR 30–49 mL/min/1.73 m2 stratum: HR 0.62, 95% CI 0.49–0.78; Pinteraction = 0.89]. Despite receiving lower Eplerenone doses, patients in the eGFR 30–49 mL/min/1.73 m2 stratum more often had hyperkalaemia, renal failure events, and drug discontinuation. Conclusion: In EMPHASIS‐HF the Eplerenone dose was stratified according to renal function and the treatment effect was not influenced by renal function: 25 mg/day in patients with eGFR 30–49 mL/min/1.73 m2 was as effective as 50 mg/day in patients with eGFR > =50 mL/min/1.73 m2. However, patients with impaired renal function experienced more adverse events, despite reveiving lower Eplerenone doses. Current guidelines do not recommend tailoring the dose of eplereone according to renal function but the current data suggest they should.

  • impact of Eplerenone on major cardiovascular outcomes in patients with systolic heart failure according to baseline heart rate
    Clinical Research in Cardiology, 2019
    Co-Authors: Ken Lee Chin, John J V Mcmurray, Dirk J Van Veldhuisen, Karl Swedberg, Stuart J Pocock, John Vincent, Bertram Pitt, T Collier, Faiez Zannad
    Abstract:

    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.

  • antihypertensive effect of the mineralocorticoid receptor antagonist Eplerenone a pooled analysis of patient level data from comparative trials using regulatory approved doses
    Vascular Health and Risk Management, 2018
    Co-Authors: Mireille Fernet, Paula Abreu, John Vincent, Katharina Lins, Bruce Beckerman, Ellen Burgess
    Abstract:

    Purpose Several options are available for the treatment of hypertension; however, many treated patients are still not below blood pressure (BP) target. Eplerenone, a selective mineralocorticoid receptor antagonist, is an approved treatment option for the management of patients with hypertension in a number of countries. This patient-level pooled analysis was conducted to document the efficacy and safety/tolerability of Eplerenone at the dosages approved for use in hypertension in comparison to placebo or other approved antihypertensive agents. Methods Seventeen Phase III studies conducted in patients with mild-to-moderate hypertension in the Eplerenone Hypertension Clinical Program were reviewed; eleven met the selection criteria. The primary endpoint was change from baseline in seated diastolic BP and seated systolic BP measured at the end of the study. Results A total of 2,698 patients were included in this per-protocol analysis. In patients treated for at least 6 weeks with a stable dose of Eplerenone, doses of 50 mg daily and 100 mg daily were associated with greater reductions of seated systolic BP and seated diastolic BP compared with placebo (P 6.0 mmol/L) occurred in up to 0.4% in the Eplerenone groups, 0.4% in the placebo group, and 0.1% in the active-control group. Conclusion This patient-level pooled analysis provides robust evidence that Eplerenone, at 50 mg or 100 mg daily, was effective in lowering BP in patients with mild-to-moderate hypertension and was well tolerated.

  • aspirin does not reduce the clinical benefits of the mineralocorticoid receptor antagonist Eplerenone in patients with systolic heart failure and mild symptoms an analysis of the emphasis hf study
    European Journal of Heart Failure, 2016
    Co-Authors: Ken Lee Chin, John J V Mcmurray, Dirk J Van Veldhuisen, Karl Swedberg, Stuart J Pocock, John Vincent, Bertram Pitt, T Collier, Eva Turgonyi
    Abstract:

    AimsIt 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 >5.5mmol/L] in the Eplerenone in Mild Patients Hospitalization and SurvIval Study in Heart Failure trial (EMPHASIS-HF). Methods and resultsPatients 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. ConclusionAspirin 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.