Effects of spironolactone on cardiovascular outcomes in chronic kidney disease and end-stage renal disease patients

Cardiovascular disease causes significant morbidity and mortality among patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD). Several small clinical trials have shown the beneficial effects of spironolactone therapy on cardiac function in CKD patients. However, the effect of spironolactone on cardiovascular outcomes in CKD and ESRD patients is not clear. The objective of this study was to systematically review data regarding the effects of spironolactone on cardiac morphology, function and mortality in these patient populations. We searched Embase, PubMed, and Cochrane Central Register of Controlled Trials databases up to March 2015 for English-language, human-subjects clinical trials that evaluated cardiovascular outcomes with spironolactone use in CKD and ESRD patients. Data extracted from the literature were analyzed with the Review Manager. Seven randomized controlled trials (RCTs) involving 737 patients were included. Ejection fraction (EF) was not significantly improved with spironolactone treatment (P = 0.78). However, compared with the use of placebo alone, spironolactone therapy decreased left ventricular mass (LVM) (P = 0.03). Spironolactone was superior to placebo in reducing cardiovascular mortality (P = 0.03) and all-cause mortality (P = 0.0005), whereas the occurrence of hyperkalemia was similar between placeboand spironolactone-treated patients (P = 0.16). These findings suggest that spironolactone has beneficial effects on LVM and reduces the risk of cardiovascular and all-cause mortality without increasing the incidence of hyperkalemia in CKD and ESRD patients, but it does not seem to improve the cardiac function index. The potential effects of spironolactone therapy on cardiovascular outcomes require further study.