Mineralocorticoid receptor antagonists therapy in transthyretin amyloid cardiomyopathy: a propensity-matched cohort study

Background

Evidence for mineralocorticoid receptor antagonists (MRA) in heart failure (HF) secondary to transthyretin amyloid cardiomyopathy (ATTR-CM) is limited.

Purpose

Evaluate the impact of MRA on clinical outcomes in ATTR-CM.

Methods

Single-center, retrospective cohort of consecutive patients with confirmed ATTR-CM (2014–2023; n=111). Patients were categorized as MRA-treated or untreated. Propensity score (PS) matching used 11 clinical covariates, yielding 26 matched pairs (n=52). The primary outcome was all-cause mortality; secondary outcomes included heart failure hospitalization (HFH) and a composite of mortality and HFH. Survival was analyzed using Kaplan–Meier estimates and Cox regression, with treatment modeled both at baseline and as a time-varying covariate to account for immortal time bias.

Results

In the PS-matched cohort (mean age 81.0±4.6 years, 61.5% male), MRA therapy was not associated with a reduction in all-cause mortality (HR=0.71 [0.28–1.81] p=0.48), over a median follow-up of 23 months (IQR: 16–41.25). In the overall (unmatched) cohort, MRA therapy was also not associated with mortality (HR=0.93 [0.50–1.72] p=0.82). In time-varying Cox models, MRA treatment remained neutral both unadjusted (HR=0.96 [0.44–2.08] p=0.92) and after multivariable adjustment for age, sex, comorbidities, and concurrent HF therapies (HR=1.35 [0.62–2.95] p=0.45).

Similarly, no significant association was observed between MRA therapy and HF hospitalization. In the PS-matched cohort, the HR for HFH was 0.71 [0.28–1.81] (p=0.48), consistent with findings in the unmatched cohort (HR=0.93 [0.50–1.72] p=0.82). In time-varying analyses, MRA remained neutral both unadjusted (HR=0.96 [0.44–2.08] p=0.92) and adjusted (HR=1.35 [0.62–2.95] p=0.45).

The composite endpoint of all-cause mortality or HF hospitalization was likewise unaffected by MRA use (PS-matched HR=0.71[0.28–1.81] p=0.48), with consistent null findings in time-varying unadjusted and adjusted analyses.

Conclusions

In this PS-matched observational cohort of ATTR-CM, MRA therapy was not associated with improved survival, fewer HFH, or lower composite event rates. Findings were consistent across baseline and time-varying analyses, suggesting no apparent benefit of MRA therapy in this population. Prospective, adequately powered studies are warranted to clarify the role of MRA in ATTR-CM.For image description, please refer to the figure legend and surrounding text.