Mineralocorticoid receptor antagonists in patients with transthyretin amyloid cardiomyopathy receiving disease-modifying therapy

BACKGROUND: Whether mineralocorticoid receptor antagonists (MRAs) confer incremental clinical benefit in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) treated with disease-modifying therapy remains uncertain. We aimed to assess the effectiveness and safety of MRAs in patients with ATTR-CM receiving disease-modifying therapy. METHODS: This retrospective cohort study used data from the TriNetX US database to identify adult patients with ATTR-CM who initiated disease-modifying therapy (tafamidis or vutrisiran) within 1 year of incident heart failure (HF) diagnosis between 1 September 2019 and 10 December 2025. Patients were categorised as MRA users or non-users and were matched based on 1:1 propensity-score matching. The primary effectiveness endpoint was a composite of all-cause mortality or HF hospitalisation (HFH). Secondary effectiveness endpoints were all-cause mortality, HFH and ventricular arrhythmia (VA). The safety endpoint was hyperkalaemia. RESULTS: Among 4598 patients with ATTR-CM (mean (SD) age, 77.6 (8.4) years; 3726 (81.0%) men) treated with tafamidis (n=4386) or vutrisiran (n=377), 505 MRA users were matched to 505 non-users. MRA use was not associated with significant reductions in all-cause mortality or HFH (HR 1.04; 95% CI 0.82 to 1.32; p=0.73). There was no significant difference in all-cause mortality (HR 1.00; 95% CI 0.70 to 1.46; p=0.96), HFH (HR 1.09; 95% CI 0.84 to 1.43; p=0.48) and VA (HR 1.07; 95% CI 0.77 to 1.48; p=0.67). Hyperkalaemia was not significantly higher in MRA users (HR 1.13; 95% CI 0.89 to 1.44; p=0.29) compared with non-users. CONCLUSIONS: In a contemporary cohort of patients with ATTR-CM treated with disease-modifying therapy, MRA use was associated with limited incremental clinical benefits.