João Pedro Ferreira1,2, Paula Abreu3, John J V McMurray4, Dirk J van Veldhuisen5, Karl Swedberg6, Stuart J Pocock7, John Vincent3, Katharina Lins3, Patrick Rossignol1, Bertram Pitt8, Faiez Zannad1. 1. National Institute of Health and Medical Research (INSERM), Center for Clinical Multidisciplinary Research 1433, INSERM U1116, University of Lorraine, Regional University Hospital of Nancy, French Clinical Research Infrastructure Network (F-CRIN) Investigation Network Initiative-Cardiovascular and Renal Clinical Trialists (INI-CRCT), Nancy, France. 2. Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, Cardiovascular Research and Development Unit, University of Porto, Porto, Portugal. 3. Pfizer Inc., New York, NY, USA. 4. BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, UK. 5. Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. 6. Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden. 7. Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK. 8. Department of Medicine, University of Michigan School of Medicine, Ann Arbor, MI, USA.
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 eGFRstratum [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.
RCT Entities:
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.
Authors: Rajiv Agarwal; Amer Joseph; Stefan D Anker; Gerasimos Filippatos; Peter Rossing; Luis M Ruilope; Bertram Pitt; Peter Kolkhof; Charlie Scott; Robert Lawatscheck; Daniel J Wilson; George L Bakris Journal: J Am Soc Nephrol Date: 2021-11-03 Impact factor: 10.121
Authors: Ravi B Patel; Gregg C Fonarow; Stephen J Greene; Shuaiqi Zhang; Brooke Alhanti; Adam D DeVore; Javed Butler; Paul A Heidenreich; Joanna C Huang; Michelle M Kittleson; Karen E Joynt Maddox; James J McDermott; Anjali Tiku Owens; Pamela N Peterson; Scott D Solomon; Orly Vardeny; Clyde W Yancy; Muthiah Vaduganathan Journal: J Am Coll Cardiol Date: 2021-05-11 Impact factor: 27.203
Authors: Edmund Ym Chung; Marinella Ruospo; Patrizia Natale; Davide Bolignano; Sankar D Navaneethan; Suetonia C Palmer; Giovanni Fm Strippoli Journal: Cochrane Database Syst Rev Date: 2020-10-27