Impact of Aldosterone Antagonists on Sudden Cardiac Death Prevention in Heart Failure and Post-Myocardial Infarction Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Abstract

Background and ObjectivesSudden cardiac death (SCD) is a severe burden of modern medicine. Aldosterone antagonist is publicized as effective in reducing mortality in patients with heart failure (HF) or post myocardial infarction (MI). Our study aimed to assess the efficacy of AAs on mortality including SCD, hospitalization admission and several common adverse effects.MethodsWe searched Embase, PubMed, Web of Science, Cochrane library and clinicaltrial.gov for randomized controlled trials (RCTs) assigning AAs in patients with HF or post MI through May 2015. The comparator included standard medication or placebo, or both. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Event rates were compared using a random effects model. Prospective RCTs of AAs with durations of at least 8 weeks were selected if they included at least one of the following outcomes: SCD, all-cause/cardiovascular mortality, all-cause/cardiovascular hospitalization and common side effects (hyperkalemia, renal function degradation and gynecomastia).ResultsData from 19,333 patients enrolled in 25 trials were included. In patients with HF, this treatment significantly reduced the risk of SCD by 19% (RR 0.81; 95% CI, 0.67–0.98; p = 0.03); all-cause mortality by 19% (RR 0.81; 95% CI, 0.74–0.88, p<0.00001) and cardiovascular death by 21% (RR 0.79; 95% CI, 0.70–0.89, p<0.00001). In patients with post-MI, the matching reduced risks were 20% (RR 0.80; 95% CI, 0.66–0.98; p = 0.03), 15% (RR 0.85; 95% CI, 0.76–0.95, p = 0.003) and 17% (RR 0.83; 95% CI, 0.74–0.94, p = 0.003), respectively. Concerning both subgroups, the relative risks respectively decreased by 19% (RR 0.81; 95% CI, 0.71–0.92; p = 0.002) for SCD, 18% (RR 0.82; 95% CI, 0.77–0.88, p < 0.0001) for all-cause mortality and 20% (RR 0.80; 95% CI, 0.74–0.87, p < 0.0001) for cardiovascular mortality in patients treated with AAs. As well, hospitalizations were significantly reduced, while common adverse effects were significantly increased.ConclusionAldosterone antagonists appear to be effective in reducing SCD and other mortality events, compared with placebo or standard medication in patients with HF and/or after a MI.

Effectiveness of drug interventions to prevent sudden cardiac death in patients with heart failure and reduced ejection fraction: an overview of systematic reviews

“… 59 Mineralocorticoid receptor antagonists or antialdosterone drugs have been reported effective in HFrEF by reducing SCD and all-cause mortality. 21 22 54 60 Our summary of the findings and the consistency of the results support this claim with a high quality of evidence. Only one retrieved meta-analysis 23 supported the effectiveness of combined ARB/neprilysin inhibitor.…”

“…Published studies about mineralocorticoid receptor antagonists (antimineralocorticoids) or (so-called) antialdosterones appeared effective in SCD and all-cause mortality prevention. 21 22 54 However, in a recent systematic review, 21 adverse effects (hyperkalaemia, degradation of renal function and gynaecomastia) were significantly higher in the antialdosterone-treated group compared with placebo. The quality of the evidence was rated high with relative effect for SCD (RR 0.81, 95% CI (0.67 to 0.98)) and all-cause mortality (RR 0.81, 95% CI (0.74 to 0.88)) ( table 2 ).…”

Plasma endothelin-1-related peptides as the prognostic biomarkers for heart failure

“…The value of I 2 between 0 and 25% represents insignificant heterogeneity, 26 and 50% as low heterogeneity, 51 and 75% as moderate heterogeneity, and more than 75% as high heterogeneity. [ 24 ] Subgroup analysis was performed to explore the sources of heterogeneity. Evidence of publication bias was assessed with funnel plots by Egger's and Begg's linear regression.…”

The novel mineralocorticoid receptor antagonist finerenone attenuates neointima formation after vascular injury

“…Direct deleterious effects of aldosterone and mineralocorticoid receptor (MR) activation occur in both the heart and kidneys [ 2 ]. MR blockade prevents some of these detrimental effects and markedly improves morbidity and mortality of patients with moderate to severe heart failure as evidenced by large randomized controlled clinical multi-center trials [ 3 – 6 ]. De Boer and colleagues showed that MRA use markedly increased over the last 20 years among patients with diabetic kidney disease, who are at high risk for vascular complications [ 7 ].…”