Aldosterone Antagonists Reduce the Risk of Cardiovascular Mortality in Dialysis Patients: A Meta-Analysis

Abstract

Background and Purpose. Cardiovascular disease is the major cause of death in dialysis patients. Although aldosterone antagonists were considered a treatment for severe heart failure patients to reduce cardiac mortality, whether treating patients undergoing maintenance dialysis with aldosterone antagonists could reduce the risk of cardiocerebrovascular (CCV) remains unclear. We aim to systematically assess the efficacy and tolerability of the addition of aldosterone antagonists to conventional therapy in patients undergoing maintenance dialysis. Materials and Methods. We searched PubMed, EMBASE, the Cochrane Library, the Chinese Biomedical Literature Database (CBM), and the China National Knowledge Infrastructure (CNKI) for relevant articles. The primary endpoint of interest was CCV mortality. The secondary endpoints were all-cause mortality, left ventricular mass index (LVMI), and left ventricular ejection fraction (LVEF). Publication bias was evaluated using funnel plots and Egger’s test. The meta-analysis was performed using Review Manager software version 5.3. Results. This analysis included 10 randomized controlled trials (RCTs) with 1172 total chronic dialysis patients. The use of aldosterone antagonists in the dialysis population resulted in a marked reduction in CCV mortality (RR 0.42, 95% CI 0.26-0.65, P=0.0002) and all-cause mortality (RR0.46, 95%CI 0.32-0.66, P<0.0001). The LVEF was improved by treatment with aldosterone antagonists (WMD 6.35%, P<0.00001). Moreover, aldosterone antagonists decreased the LVMI (WMD -8.69 g/m2, P=0.0006), whereas aldosterone antagonists increased the occurrence of hyperkalemia (RR1.70, 95%CI 1-2.88, P=0.05) and gynecomastia (RR 8.01, 95% CI 2.44- 26.27, P=0.0006). Conclusions. Addition of aldosterone antagonists to conventional treatment in chronic dialysis patients may reduce CCV mortality, improve cardiac function, and simultaneously decrease LVMI.

Heart Failure in Patients with Chronic Kidney Disease

“…Aldosterone breakthrough is accompanied by lower plasma renin activity (PRA), which is expressed as a rise in the aldosterone-to-renin ratio (more than 3 ng/dL per ng/mL/h) and reflects the volume expansion caused by aldosterone [ 63 , 64 ]. Several studies have shown that in CKD, the non-selective MRAs (spironolactone or eplerenone), when given on top of ACEi or ARBs, reduce proteinuria but increase potassium levels, and these agents may be beneficial in dialysis patients [ 65 , 66 , 67 ]. However, a small trial in dialysis patients showed no benefit [ 68 ].…”

Acción de la aldosterona y el receptor de mineralocorticoides en insuficiencia renal crónica y falla cardiaca

“…En pacientes con terapia dialítica, el estudio DOHAS (Dialysis outcomes heart failure aldactone study) (22) analizó a 309 sujetos en hemodiálisis, con 25 mg/día de espironolactona vs. terapia convencional, observándose una reducción de la mortalidad o ingreso por eventos cardiovasculares en el grupo de espironolactona (HR 0,40 con IC del 95 %, 0,20-0,80; p valor = 0,017). Un 1,9 % del grupo de espironolactona presentó hiperkalemia severa y 10,2 % ginecomastia o mastodinia, en otros 2 metaanálisis tuvieron resultados semejantes (23,24). Actualmente se encuentran en marcha dos ensayos clínicos para tener más claridad en este grupo de pacientes, el ALCHEMIST (Aldosterone antagonist chronic hemodyalisis interventional survival trial) y el ACHIEVE (Aldosterone blockade for health improvement evaluation in end-stage renal disease) (6).…”

Safety and Efficacy of Spironolactone in Dialysis-Dependent Patients: Meta-Analysis of Randomized Controlled Trials

“…Flevari et al ( 9 ) found significant increased sodium potassium level and decreased blood pressure after MRAs treatment, while Lin et al ( 10 ) and Gross et al ( 11 ) suggested unchanged serum potassium and blood pressure, respectively. Previous meta-analyses have been limited by small number of clinical trials ( 12 ) or results for single system ( 13 ). Thus, spironolactone is not widely understood in subjects undergoing dialysis.…”