- Design
- Patient-level pooled cohort analysis with meta-analysis
- Population
- 1,019 patients with heart failure in four cohorts, plus EARLIER and EPHESUS
- Primary outcome
- Clinical outcomes with MRA use by pre-treatment aldosterone
- Effect
- High aldosterone HR 0.63 (0.42-0.92); low aldosterone HR 1.66 (1.12-2.45)
A patient-level analysis in the European Heart Journal, published on 9 October 2026, pooled four heart failure cohorts (DOSE, CARRESS-HF, MDR and TOPCAT; 1,019 patients) and meta-analysed outcomes with the EARLIER and EPHESUS trials. Mineralocorticoid receptor antagonist use was associated with higher median aldosterone, 310 against 174 pg/mL. In the MDR cohort, urine sodium-to-potassium ratio was used as a marker of receptor activity, and more aldosterone was needed on an MRA to produce the same receptor activity.
The association between MRA use and outcomes depended on aldosterone before treatment (P for interaction 0.005). With high pre-treatment aldosterone, MRA use was associated with better outcomes (HR 0.63, 95% CI 0.42 to 0.92). With low pre-treatment aldosterone, it was associated with worse outcomes (HR 1.66, 95% CI 1.12 to 2.45).
The authors are explicit that this is hypothesis-generating and that MRAs remain guideline-directed therapy with proven population benefit. Its value is in raising the question of whether the low doses commonly used are enough, and whether aldosterone could one day guide dosing.
- Keep prescribing MRAs to eligible patients with heart failure as guidelines recommend.
- Do not measure aldosterone to decide on MRA therapy on the basis of this analysis.
- Continue to monitor potassium and creatinine after starting or uptitrating an MRA.
- Watch for trials testing aldosterone-guided or higher-dose MRA strategies.
Why it matters
It challenges the assumption that a low fixed MRA dose blocks the receptor adequately in everyone.
Don't overread it
Pooled observational and post hoc data — it cannot show that MRAs harm patients with low aldosterone.
The statistics, in plain English
The two hazard ratios point in opposite directions, and the interaction P of 0.005 suggests the difference is unlikely to be chance. But the comparison is not randomised by aldosterone level, and the lower confidence limits (0.92 and 1.12) are close to 1, so the size of both effects is uncertain.
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