Effect of spironolactone on the risks of mortality and hospitalization for heart failure in pre-dialysis advanced chronic kidney disease: A nationwide population-based study

Background: Spironolactone has been shown to reduce cardiovascular death in patients with mild-to-moderatechronic kidney disease (CKD), but its risks and benefits in advanced CKD remain unsettled. We aimed to assess whether spironolactone reduces cardiovascular mortality and morbidity in pre-dialysis stage 5 CKD patients. Methods: Using Taiwan's National Health Insurance Research Database from January 2000 to June 2009, we enrolled 27,213 pre-dialysis stage 5 CKD adult patients, inwhom1363 patientswere treatedwith spironolactone (user) and 25,850were not (nonuser). Outcomeswere all-causemortality, hospitalization for heart failure (HHF) and major adverse cardiac event (MACE, the composite of acute myocardial infarction and ischemic stroke). Patients were followed up till December 31, 2009. Results: Over 85,758 person-years of follow-up, spironolactone users had higher incidence for all-causemortality (24.7/100 person-years vs. 10.6/100 person-years), infection-related death (4.4/100 person-years vs. 1.7/100 person-years) and HHF (4.0/100 person-years vs. 1.4/100 person-years). Multivariable Cox hazards model showed that spironolactone users were associated with higher risks of all-cause mortality (adjusted hazard ratio [aHR] 1.35, 95% confidence interval [CI] 1.24-1.46), infection-related death (aHR 1.42, CI 1.16-1.73) and HHF (aHR 1.35, CI 1.08-1.67) as compared to nonusers. The risks for cardiovascular mortality, MACE and hyperkalemia-associated hospitalization were similar between two groups. After matching users and nonusers (1: 3 ratio) by propensity scores, the results were consistent in matched cohort and across subgroups. Conclusions: Spironolactone may be associatedwith higher risks for all-cause and infection-related mortality and HHF in pre-dialysis stage 5 CKD patients. Spironolactone should be used with caution in advanced CKD patients. (C) 2017 Elsevier B. V. All rights reserved.