TABLE 2.

Effects of mineralocorticoid receptor antagonists for the development of cardiovascular disease in pre-dialysis or on-dialysis patients with CKD.

RAAS blocker class	Authors, Year; Reference number	Patients	Study design	Study protocol	Results
Mineralocorticoid receptor antagonists	Eschalier et al., 2013; 5	N = 912 eGFR 30 < 60 (mL/min/1.73 m2) Chronic heart failure with reduced ejection fraction <35 %	RCT; Multicenter double-blind placebo-controlled clinical trial	Eplerenone 25–50 mg once daily or placebo; 3 years	Compared with placebo, eplerenone reduced the risk of cardiovascular events, including hospitalization for heart failure or cardiovascular mortality, compared with placebo in patients with CKD (HR, 0.62; 95% CI, 0.49 to 0.79; p = 0.0001).
	Tsujimoto and Kajio et al., 2018; 27	N = 1465; eGFR 30 < 60 (mL/min/1.73 m2) or urine albumin-to-creatinine ratio >30 mg/gCre; Left ventricular ejection fraction >45%	RCT; Multicenter double-blind placebo-controlled clinical trial	Spironolactone or placebo (Dose was not shown); 6 years	Compared with placebo, spironolactone reduced cardiovascular events, including non-fatal myocardial infarction, non-fatal stroke or hospitalization for heart failure, in patients associated with CKD (HR, 0.75; 95% CI, 0.60 to 0.95; p = 0.01).
	Lin et al., 2016; 14	N = 253; Hemodialysis	RCT; Multicenter double-blind placebo-controlled clinical trial	Spironolactone 25 mg or placebo per day after hemodialysis or in the morning; 2 years	Compared with placebo, spironolactone reduced the risk of a composite death from cardiocerebrovascular events, including new occurrence or exacerbation of heart failure that was not improved by water removal through dialysis, ventricular fibrillation, or sustained ventricular tachycardia, new or recurrent acute myocardial infarction, new occurrence or exacerbation of angina pectoris, dissecting aneurysm of the aorta, stroke, and new or recurrent transient ischemic attack in patients on maintenance hemodialysis (HR, 0.42; 95% CI, 0.26 to 0.78; p = 0.017).
	Walsh et al., 2015; 28	N = 146; Dialysis, including hemodialysis and peritoneal dialysis	RCT; Multicenter double-blind placebo-controlled clinical trial; Secondary outcomes	Eplerenone 50 mg or placebo per day; 13 weeks	Compared with placebo, eplerenone did not reduce the risk of cardiovascular events in patients on maintenance hemodialysis (relative risk, 0.7; 95% CI, 0.2 to 2.3; p value was not shown.).

CI, confidence interval; CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; HR, hazard ratio; RAAS, renin–angiotensin–aldosterone system; RCT, randomized controlled trial