Author + information
- Received July 8, 2019
- Revision received August 16, 2019
- Accepted August 20, 2019
- Published online November 25, 2019.
- João Pedro Ferreira, MD, PhDa,∗ (, )
- Xavier Rossello, MD, PhDb,c,
- Romain Eschalier, MD, PhDd,
- John J.V. McMurray, MDe,
- Stuart Pocock, PhDf,
- Nicolas Girerd, MD, PhDa,
- Patrick Rossignol, MD, PhDa,
- Bertram Pitt, MDg and
- Faiez Zannad, MD, PhDa
- aUniversité de Lorraine, Centre d'Investigation Clinique-Plurithématique INSERM 1433, and Cardiovascular and Renal Clinical Trialists, INSERM U1116, CHRU Nancy Brabois, Nancy, France
- bDepartment of Cardiology, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain
- cDepartment of Cardiology, CIBER de enfermedades Cardio Vasculares, Madrid, Spain
- dDépartement de Cardiologie, Hôpital Gabriel Montpied, CHU de Clermont-Ferrand, Clermont-Ferrand, France
- eBritish Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, United Kingdom
- fDepartment of Cardiology, London School of Hygiene and Tropical Medicine, London, United Kingdom
- gDepartment of Medicine, University of Michigan School of Medicine, Ann Arbor, Michigan
- ↵∗Address for correspondence:
Dr. João Pedro Ferreira, Centre d’Investigations Cliniques, INSERM CHRU de Nancy, Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu, 4 Rue du Morvan, Vandoeuvre lès Nancy 54500, France.
Objectives This study sought to assess the effect of MRA treatment (vs. placebo) in older patients (≥75 years of age) compared with younger patients (<75 years of age) with heart failure (HF).
Background Mineralocorticoid receptor antagonists (MRAs) have been shown to reduce morbidity and mortality in patients with HF with reduced ejection fraction (HFrEF) and in a subset of patients with HF with preserved EF (HFpEF). Notwithstanding, MRAs are underused, especially in the elderly. Pooling the individual patient data (IPD) provided more statistical power with which to assess the efficacy and safety of MRA treatment in this subpopulation.
Methods An IPD meta-analysis was performed using Cox proportional hazards models stratified by trial. A total of 1,756 patients (853 randomized to placebo and 903 to MRA) ≥75 years of age, along with 4,411 patients (2,242 randomized to placebo and 2,169 to MRA) <75 years of age were included. The primary outcome was a composite of death from cardiovascular causes or hospitalization for HF.
Results The treatment groups were well balanced. Patients ≥75 years of age or older and those 80 years of age, 61% were male, 30% had diabetes, and the mean estimated glomerular filtration rate 59 ml/min. The primary outcome occurred in 331 patients (38.8%) in the placebo group versus 281 (31.1%) in the MRA group (hazard ratio: 0.74; 95% confidence interval: 0.63 to 0.86; p < 0.001; and the heterogeneity p value [heterogeneity p = Cochran's Q p value of treatment effect by study interaction] was 0.52). Cardiovascular death and all-cause death were also reduced by MRAs without significant between-trial or age (younger vs. older) heterogeneity. Worsening renal function and hyperkalemia occurred more frequently in patients taking MRAs (vs. placebo). Compared to younger patients, worsening renal function (but not hyperkalemia) was found more frequently in the elderly.
Conclusions MRAs reduced morbidity and mortality in elderly patients with HF, a beneficial effect that is more marked in patients with HFrEF but homogenous across HFrEF and HFpEF. Implementation of measures that increase MRA treatment in this population are warranted.
Drs. Ferreira, Rossignol, and Zannad are supported by French National Research Agency Fighting Heart Failure grant ANR-15-RHU-0004, French PIA project Lorraine Université d’Excellence GEENAGE grant ANR-15-IDEX-04-LUE, Contrat de Plan Etat Région Lorraine, and FEDER grant IT2MP. Dr. Rossello has received support from the SEC-CNIC CARDIOJOVEN fellowship program. Dr. Rossignol has received research and travel support from Novartis; and has received personal fees from NovoNordisk, Relypsa, Vifor, Vifor Fresenius Medical Care, AstraZeneca, GrÜnenthal, Idorsia, Bayer, Servier, Corvidia, G3 pharmaceuticals, and CardioRenal (cofounder). Dr. Girerd has received honoraria from Novartis and Boehringer Ingelheim. Dr. Pitt is a consultant for Bayer, Sanofi, AstraZeneca, KBP Biosciences, and Vifor. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received July 8, 2019.
- Revision received August 16, 2019.
- Accepted August 20, 2019.
- 2019 American College of Cardiology Foundation
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