Renal function stratified dose comparisons of eplerenone versus placebo in the EMPHASIS-HF trial
Journal article
Ferreira, João Pedro, Abreu, Paula, McMurray, John J. V., van Veldhuisen, Dirk J., Swedberg, Karl, Pocock, Stuart J., Vincent, John, Lins, Katharina, Rossignol, Patrick, Pitt, Bertram and Zannad, Faiez. (2019). Renal function stratified dose comparisons of eplerenone versus placebo in the EMPHASIS-HF trial. European Journal of Heart Failure. 21(3), pp. 345 - 351. https://doi.org/10.1002/ejhf.1400
Authors | Ferreira, João Pedro, Abreu, Paula, McMurray, John J. V., van Veldhuisen, Dirk J., Swedberg, Karl, Pocock, Stuart J., Vincent, John, Lins, Katharina, Rossignol, Patrick, Pitt, Bertram and Zannad, Faiez |
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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. |
Keywords | eplerenone; heart failure; treatment dose; renal function; stratification |
Year | 2019 |
Journal | European Journal of Heart Failure |
Journal citation | 21 (3), pp. 345 - 351 |
Publisher | John Wiley & Sons |
ISSN | 1388-9842 |
Digital Object Identifier (DOI) | https://doi.org/10.1002/ejhf.1400 |
Scopus EID | 2-s2.0-85061573295 |
Page range | 345 - 351 |
Research Group | Mary MacKillop Institute for Health Research |
Publisher's version | File Access Level Controlled |
Place of publication | Netherlands |
https://acuresearchbank.acu.edu.au/item/8q607/renal-function-stratified-dose-comparisons-of-eplerenone-versus-placebo-in-the-emphasis-hf-trial
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