Heart failure & cardiomyopathies
Blood aldosterone concentrations and effects of mineralocorticoid receptor antagonists in heart failure
Authors' conclusion
Low-dose MRAs significantly increase aldosterone but inadequately block MR activity (measured by urine Na/K) at these new higher aldosterone concentrations. In patients with high pre-MRA aldosterone, MRA use is associated with improved MR activity and clinical outcomes. However, in patients with lower pre-MRA aldosterone concentrations, MRA use is associated with worsened MR activity and clinical outcomes.
Study context
- Population
- Heart failure (HF) cohorts with MRA exposure and plasma aldosterone concentrations availablepooled cohort
- Participants
- 1,019 participants
- Comparison
- MRA vs no MRA, by pre-MRA aldosterone concentration
- Outcome
- Effect of baseline and change in aldosterone concentrations during MRA therapy on MR activity and clinical outcomes
Methodological detailspooled cohorts (DOSE, CARRESS-HF, MDR, TOPCAT), meta-analysis with EARLIER and EPHESUS trials
- Pooled cohorts (DOSE, CARRESS-HF, MDR, TOPCAT)
- Meta-analysis with EARLIER and EPHESUS trials
Pooled result
As reported in the abstract
Clinical outcomes with MRA use, by pre-MRA aldosterone (subgroups)
MRA vs No MRAHazard ratio (95% CI)P value
High pre-MRA aldosterone
.63(.42-.92)
P = 0.02Low pre-MRA aldosterone
1.66(1.12–2.45)
P = 0.01- Association of MRA use with clinical outcomes dependent on pre-MRA aldosterone
- P for interaction = 0.005
Further pooled results
Aldosterone concentration (pooled cohort)
P < 0.001
| Outcome | MRA | No MRA | P value |
|---|---|---|---|
| Correlation of aldosterone with MR activity (MDR cohort, n = 136)Higher aldosterone required on MRA for same MR activity | −.52 | −.44 | P for interaction = 0.65 |
| P | P < .001 | P < .001 | |
| Change in urine Na/K after MRA initiation, by pre-MRA aldosterone (MDR cohort)High aldosterone vs Low aldosterone | P < 0.001 |
- Change in urine Na/K after MRA initiation, by pre-MRA aldosterone (MDR cohort): High aldosterone median change 1.4 (IQR 1.1–2.9)
- Change in urine Na/K after MRA initiation, by pre-MRA aldosterone (MDR cohort): Low aldosterone median change −.9 (IQR −2.1, −.1)
- Change in urine Na/K after MRA initiation, by pre-MRA aldosterone (MDR cohort): Mineralocorticoid receptor (MR) activity reduced with high, increased with low pre-MRA aldosterone
Original publication
Blood aldosterone concentrations and effects of mineralocorticoid receptor antagonists in heart failure. Eur Heart J. Published 16 June 2026. doi:10.
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