Abstract Body (Do not enter title and authors here):
Background: Mineralocorticoid receptor antagonists namely, Spironolactone and Eplerenone, have been cornerstone therapies for reducing morbidity and mortality in patients with heart failure. However, the comparative efficacy and safety profiles of Spironolactone and Eplerenone in patients with heart failure and reduced ejection fraction have been largely unknown.

Hypothesis: We hypothesize that Eplerenone is more efficacious and safer than Spironolactone in treating patients with heart failure and reduced ejection fraction.

Methods: We conducted a comprehensive literature search in electronic databases such as PubMed, GoogleScholar, ScienceDirect, Cochrane library, PLOSONE and Clinicaltrial.gov, including studies published within the last 10 years.We used RevMan 5.4.1 version to make statistical calculations and random effects model to calculate the pooled mean difference(MD) and relative risk(RR) values with their corresponding 95% confidence intervals(CI). A p-value of <0.005 was considered statistically significant.

Results: A total of 1296 participants (Spironolactone:647 and Eplerenone:649) from three Randomized trials and three cohorts were included in this study. The mean age of participants were 59.74±12.47 and 60.35±10.99 years with 67.12% and 66.52% males along baseline Left Ventricular ejection fraction(LVEF) of 33.47±7.77 and 32.48±8.37% in spironolactone and eplerenone groups respectively. During follow-up, eplerenone improved LVEF(MD,2.96,95%CI:2.12-3.81,I2=0%,p=<0.05), reduced Left Ventricular end systolic volume(MD,-11.50,95%CI:-14.98 to -8.03,I2=0%,p=<0.05), Left Ventricular end diastolic volume(MD,-7.99,95%CI:-15.07 to -0.90,I2=0%,p=0.03) and all-cause mortality(RR,0.70,95%CI:0.52-0.93,I2=0,p=0.02). Although insignificant, eplerenone reduced cardiovascular death or hospitalization(RR,0.95,95%CI:0.79-1.15,I2=0,p=0.60) and safety outcomes like hyperkalemia(RR,0.70,95%CI:0.45-1.09,I2=0,p=0.12) and gynaecomastia(RR,0.18,95%CI:0.02-1.65,I2=71%,p=0.13).

Conclusion: In patients with heart failure with reduced ejection fraction, compared to spironolactone, eplerenone showed superiority in improving Left ventricular ejection fraction, end systolic and diastolic volumes with all-cause mortality. Although statistically insignificant, eplerenone use reduced the cardiovascular death or hospitalization and adverse events like hyperkalemia and gynaecomastia in male patients. Further, clinical trials and research are necessary to confirm the above findings.