Mineralocorticoid receptor antagonists (MRAs) failed to show a benefit and had virtually no effect on cardiovascular death in patients with kidney failure requiring maintenance hemodialysis, according to an updated systematic review and meta-analysis published Aug. 18 in The Lancet.

The new analysis included 19 randomized controlled trials published in the past decade, including the recent ALCHEMIST and ACHIEVE trials, with 4,675 patients receiving MRAs, primarily 25 mg of spironolactone.

Results revealed that in the subgroup of trials at low risk of bias (n=3,562), cardiovascular mortality was 15% (264 of 1,785 patients) in the MRA group vs. 16% (276 of 1,777) in the control group (odds ratio [OR], 0.98). The absolute risk reduction showed only one less event per 1,000 patient-years.

Findings for all-cause mortality were similar, with trials at low risk of bias showing no benefit (OR, 0.97) and no effect of MRAs on overall hospitalizations.

Other findings showed a possible increased risk of hyperkalemia events and gynecomastia or breast pain in the MRA group vs. the control group, although the absolute risks were low.

Regarding the ALCHEMIST trial (n=644), over the 33 months of median follow-up, spironolactone failed to improve cardiovascular outcomes in patients with kidney failure on hemodialysis. No significant difference was found between spironolactone and placebo in time to first major cardiovascular event (hazard ratio [HR], 1.00; p=0.98), cardiovascular death (HR, 1.26) or death from any cause (HR, 1.01). The trial was stopped early due to lack of sponsor funding.

Likewise, in the ACHIEVE trial (n=2,538), spironolactone failed to show benefit over placebo in patients undergoing maintenance dialysis for kidney failure. There were no significant differences between groups for cardiovascular mortality or hospitalization for heart failure (HR, 0.92; p=0.35), cardiovascular mortality (HR, 0.89), all-cause mortality (HR, 0.95) or first hospitalization for heart failure (HR, 0.97). The ACHIEVE trial was stopped early for futility.

Lonnie Pyne, MD, et al., conclude that in this patient population, "available evidence does not support the use of [MRAs]." Because "the risk of cardiovascular death ... remains high, ... effective therapies continue to be urgently needed."