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A Meta-analysis of Three Randomized Controlled Trials On the Impact of Mineralocorticoid Receptor Antagonists on Sudden Cardiac Death in Patients with Heart Failure and Left Ventricular Systolic Dysfunction

X. Rossello, C. Ariti, S.J. Pocock, J.J.V. McMurray, D.J. Van Veldhuisen, K. Swedberg, et al, European Heart Journal ( 2018 ) 39 ( Supplement ), 17.

Background: Sudden cardiac death (SCD) continues to be an important cause of death in patients with left ventricular systolic dysfunction (LVSD). Use of mineralocorticoid receptor antagonists (MRAs) may help attenuate this risk.

Aim: To assess the impact of MRAs on SCD in patients with LVSD.

Methods: A fixed effect meta-analysis at individual patient level was performed using 11,032 patients recruited in 3 placebo controlled randomized trials: Randomized Aldactone Evaluation Study (RALES), Eplerenone Post Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) and Eplerenone in Mild Patients Hospitalzation and Survival Study in Heart Failure (EMPHASISHF). Treatment effect was determined using a Cox proportional hazards model stratified by study.

Results: Patients receiving MRAs were at lower risk of SCD compared with controls after a mean follow-up of 18 months (HR 0.77, 95% CI: 0.66,0.89) (Figure). This effect was consistent across trials and did not change substantially after adjustment for 14 baseline covariates (HR 0.76, 95% CI: 0.65,0.89). Moreover, the benefits of MRAs were consistent across most of the study subgroups (male gender, renal dysfunction, Potassium<4 mmol/l, body mass index<25 kg/m2, ischemic heart failure, atrial fibrillation, diabetes, hypertension, NYHA class IIIIV, ejection fraction <30% and angiotensin converting enzyme inhibitors), except for age and beta blockers use. A consistent effect was also found in the stratified analysis in relevant subsets of patient defined by heart failure  (HF) cause, NYHA class or LVEF≤35% (Table). Little heterogeneity in treatment effect was observed among the three trials.

Conclusions: MRAs lowers the risk for SCD by 23% in patients with HF and LVSD and this effect was consistent across different patient severity and presentation. Optimization of the use of MRAs, on top of other evidence based medications, should be carried out in these patients.

 


Figure: Forest plot with treatment effect

 

Table: Stratified analyses for treatment effect

Source: ESC 2018 Last Modified :Aug 6, 2019.
Compiled and edited by the Editorial team and approved by Expert panel of CardioValens.com
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