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End-stage kidney disease (ESKD) patients undergoing dialysis face a high risk of cardiovascular mortality. Clinical experts have long debated the role of MRAs in dialysis patients as a potential protective therapy. Recent evidence from the ACHIEVE and ALCHEMIST trials has provided crucial clarity on this controversial topic. A new systematic review and meta-analysis of 14 randomized controlled trials (RCTs) now offers updated insights into the efficacy and safety of these agents.
The meta-analysis, which included 4,525 patients, revealed that mineralocorticoid receptor antagonists (MRAs) provide specific cardiovascular benefits. Consequently, the research showed a significant reduction in nonfatal cardiovascular disease (CVD) events. Specifically, the relative risk (RR) for these events was 0.68. This finding suggests that drugs like spironolactone may help prevent major non-lethal heart complications. However, the benefits did not extend to all areas of cardiovascular health. Despite the reduction in nonfatal events, there was no statistically significant impact on cardiovascular mortality or overall survival rates.
While the reduction in CVD events is promising, safety concerns remain paramount for clinicians. Using MRAs in dialysis patients significantly increases the risk of severe hyperkalemia. The meta-analysis reported an RR of 1.35 for elevated potassium levels. Furthermore, endocrine side effects are a common occurrence with steroidal MRAs. Patients in the treatment groups experienced much higher rates of gynecomastia and breast pain. Specifically, the risk for these side effects was over four times higher than in the control groups. Therefore, clinicians must carefully weigh the cardiovascular benefits against these significant adverse effects when considering therapy.
Overall, the results from the ACHIEVE and ALCHEMIST trials suggest a neutral effect on mortality. Although spironolactone and eplerenone can reduce non-fatal events, they do not seem to prolong life in this specific population. In addition, the high rate of trial discontinuation in some studies highlights the difficulty of maintaining long-term adherence. Doctors should prioritize frequent potassium monitoring if they choose to prescribe MRAs. Ultimately, the decision to use these medications should involve a personalized assessment of the patient's specific cardiovascular risk and their tolerance for side effects.
No, the latest meta-analysis indicates that MRAs do not significantly reduce cardiovascular or all-cause mortality in patients receiving maintenance dialysis.
The most common risks associated with MRAs include severe hyperkalemia (high potassium) and endocrine issues such as gynecomastia and breast pain.
Current evidence does not support routine use for survival. However, it may be considered for reducing nonfatal cardiovascular events in selected patients with careful monitoring.
Disclaimer: This content is for informational and educational purposes only. It does not constitute medical advice or a professional recommendation. Refer to the latest local and national guidelines for clinical practice.
References
Zhu Y et al. Mineralocorticoid receptor antagonists in dialysis patients after ACHIEVE and ALCHEMIST: updated systematic review and meta-analysis of 14 randomized trials. Ren Fail. 2026 Dec undefined. doi: 10.1080/0886022X.2026.2656561. PMID: 42056760.
Walsh M et al. Spironolactone versus placebo in patients undergoing maintenance dialysis (ACHIEVE): an international, parallel-group, randomised controlled trial. Lancet. 2025 Aug 16;406(10504):695-704.
Rossignol P et al. Spironolactone in patients on chronic haemodialysis at high risk of adverse cardiovascular outcomes (ALCHEMIST): a multicentre, double-blind, randomised, placebo-controlled trial and updated meta-analysis. Lancet. 2025 Aug 23;406(10505):811-820.
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