João Pedro Ferreira1, Xavier Rossello2, Romain Eschalier3, John J V McMurray4, Stuart Pocock5, Nicolas Girerd6, Patrick Rossignol6, Bertram Pitt7, Faiez Zannad6. 1. Université de Lorraine, Centre d'Investigation Clinique-Plurithématique INSERM 1433, and Cardiovascular and Renal Clinical Trialists, INSERM U1116, CHRU Nancy Brabois, Nancy, France. Electronic address: j.ferreira@chu-nancy.fr. 2. Department of Cardiology, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain; Department of Cardiology, CIBER de enfermedades Cardio Vasculares, Madrid, Spain. 3. Département de Cardiologie, Hôpital Gabriel Montpied, CHU de Clermont-Ferrand, Clermont-Ferrand, France. 4. British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, United Kingdom. 5. Department of Cardiology, London School of Hygiene and Tropical Medicine, London, United Kingdom. 6. Université de Lorraine, Centre d'Investigation Clinique-Plurithématique INSERM 1433, and Cardiovascular and Renal Clinical Trialists, INSERM U1116, CHRU Nancy Brabois, Nancy, France. 7. Department of Medicine, University of Michigan School of Medicine, Ann Arbor, Michigan.
Abstract
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 toplaceboand 903 to MRA) ≥75 years of age, along with 4,411 patients (2,242 randomized toplaceboand 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.
RCT Entities:
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.
Authors: Xavier Rossello; João Pedro Ferreira; Francisca Caimari; Zohra Lamiral; Abhinav Sharma; Cyrus Mehta; George Bakris; Christopher P Cannon; William B White; Faiez Zannad Journal: Clin Res Cardiol Date: 2021-04-30 Impact factor: 5.460
Authors: John G F Cleland; João Pedro Ferreira; Beatrice Mariottoni; Pierpaolo Pellicori; Joe Cuthbert; Job A J Verdonschot; Johannes Petutschnigg; Fozia Z Ahmed; Franco Cosmi; Hans-Peter Brunner La Rocca; Mamas A Mamas; Andrew L Clark; Frank Edelmann; Burkert Pieske; Javed Khan; Ken McDonald; Philippe Rouet; Jan A Staessen; Blerim Mujaj; Arantxa González; Javier Diez; Mark Hazebroek; Stephane Heymans; Roberto Latini; Stéphanie Grojean; Anne Pizard; Nicolas Girerd; Patrick Rossignol; Tim J Collier; Faiez Zannad Journal: Eur Heart J Date: 2021-02-11 Impact factor: 29.983
Authors: Inge Schjødt; Søren P Johnsen; Anna Strömberg; Adam D DeVore; Jan B Valentin; Brian B Løgstrup Journal: Circ Cardiovasc Qual Outcomes Date: 2022-03-11