The Safety of Eplerenone in Hemodialysis Patients

Abstract

Background and objectives Mineralocorticoid receptor antagonism reduces morbidity and mortality in patients with heart failure, but the safety of these drugs in patients receiving dialysis is unclear. This study evaluated whether hyperkalemia and/or hypotension limited the use of eplerenone, a selective mineralocorticoid receptor antagonist, in hemodialysis patients.Design, setting, participants, & measurements This was a randomized controlled trial of prevalent patients receiving hemodialysis at five Canadian centers. Participants were randomly allocated to 13 weeks of eplerenone titrated to 50 mg daily (n=77) or a matching placebo (n=77). The primary outcome was permanent discontinuation of the drug because of hyperkalemia or hypotension. Secondary outcomes included hyperkalemia, hypotension, and cardiovascular events.Results Seventy-five eplerenone-treated patients and 71 placebo-treated patients were included in the per protocol population. The primary outcome occurred in three patients (4.0%) in the eplerenone group and two (2.8%) in the placebo group, for an absolute risk difference of 1.2 percentage points (95% confidence interval, 24.7 to 7.1 percentage points). Eplerenone was interpreted as noninferior to placebo with respect to the primary outcome (i.e., a discontinuation rate for these reasons .10% was excluded). In the eplerenone group, nine patients (11.7%) developed hyperkalemia (potassium level .6.5 mEq/L), compared with two patients (2.6%) in the placebo group (relative risk, 4.5; 95% confidence interval, 1.0 to 20.2). There was no significant effect on predialysis or postdialysis BP.Conclusion Eplerenone increased the risk of hyperkalemia but did not result in an excess need to permanently discontinue the drug. Further trials are required to determine whether mineralocorticoid receptor antagonism improves cardiovascular outcomes in patients receiving long-term dialysis.

Safety and cardiovascular effects of mineralocorticoid receptor antagonists for patients receiving hemodialysis: a systematic review and meta-analysis

“…After full-text screening, one article was excluded as no data of serum potassium for the control group was provided. 21 Eleven studies were reported in this systematic review, among which five studies were RCTs [22][23][24][25][26] and six were non-randomized studies [27][28][29][30][31][32] ( Figure 1). …”

“…The serum potassium level at study completion was 4.9 ± 0.3 in the spironolactone group and 4.9 ± 0.7 in the control group, with no significant difference. Hussain et al, 31 Shavit et al, 29 Michea et al, 28 Gross et al, 22 Vukusich et al, 24 Feniman-De-Stefano et al 25 and Walsh et al 26 also found no significant change in the serum potassium level.…”

Mineralocorticoid receptor antagonists in dialysis patients

“…Walsh et al [47] 77 HD patients Eplerenone 50 mg/day 13 weeks Discontinuation of the drug because of hyperkalemia or hypotension was not different.…”

“…After 4 weeks, the systolic blood pressure was reduced from 166 ± 14 to 153 ± 10 mmHg (P < 0.05); however, there was no significant change in the potassium level (before -4.67 ± 0.2 mEq/l, after -4.86 ± 0.38 mEq/l, P = 0.48). In addition, Walsh et al [47] conducted a randomized, double-blinded, placebo-controlled study of 154 HD patients. In the study, 77 and 77 patients were treated with eplerenone 50 mg/day or placebo, respectively, and followed for 13 weeks.…”

Cardiac hypertrophy in chronic kidney disease—role of Aldosterone and FGF23

“…Thus, potassium secretion from the intestine is increased in patients with advanced CKD or on dialysis therapy [29,34,35], and mineralocorticoid receptor blockers are reported to suppress this mechanism [38]. Indeed, several studies have reported that the administration of spironolactone is associated with increased incidence of hyperkalemia in patients on maintenance hemodialysis therapy [63][64][65] although pronounced hyperkalemia (serum potassium ≥ 6 mEq/L) does not occur commonly [66]. Notably, there are also reported a substantial number of studies showing that spironolactone does not cause significantly higher levels of serum potassium in patients on hemodialysis [47][48][49] or peritoneal dialysis therapy [50,51,67,68], when compared with placebo (Table 1).…”