A propensity-matched cohort study on angiotensin-converting enzyme inhibitors and angiotensin ii receptor blockers therapy in transthyretin amyloid cardiomyopathy

Background

Evidence supporting the use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers (ACEI/ARB) in heart failure (HF) due to transthyretin amyloid cardiomyopathy (ATTR-CM) remains limited.

Aim

To evaluate the association between ACEI/ARB therapy and clinical outcomes in patients with ATTR-CM.

Methods

We performed a single-center, retrospective cohort study of consecutive patients with confirmed ATTR-CM diagnosed between 2014 and 2023 (n=110). Patients were classified as ACEI/ARB-treated or untreated. Propensity score (PS) matching using 12 clinical covariates yielded 28 matched pairs (n=56). The primary endpoint was all-cause mortality; secondary endpoints included HF hospitalization (HFH) and a composite of mortality and HFH. Outcomes were assessed with Kaplan–Meier estimates and Cox proportional hazards models with treatment assigned at baseline.

Results

In the PS-matched cohort (mean age 81.0±4.6 years; 61.5% male), ACEI/ARB therapy was not associated with a reduction in all-cause mortality (HR 0.86 [0.42–1.78], p=0.684) over a median follow-up of 23 months (IQR 16–41.25). Similar results were observed in the unmatched cohort (HR 0.61 [0.34–1.12], p=0.112). The annualized mortality rate was comparable between treated and untreated patients (14.4% vs 16.6% per person-year).

ACEI/ARB therapy was also not associated with a reduction in HF hospitalization. The PS-matched HR for HFH was 0.74 [0.27–2.03] (p=0.56), consistent with the unmatched cohort (HR 0.52 [0.26–1.05], p=0.07). Annualized HFH rates were similar between groups (9.9% vs 12.5% per person-year).

The composite of all-cause mortality or HF hospitalization showed no significant difference in either the unmatched (HR 0.58 [0.32–1.05], p=0.07) or PS-matched cohort (HR 0.75 [0.32–1.77], p=0.51). Annualized composite event rates were likewise similar (14.9% vs 18.9% per person-year).

Conclusions

In this propensity-matched cohort of patients with ATTR-CM, ACEI/ARB therapy was not associated with improvements in all-cause mortality, HF hospitalization, or the composite of these outcomes. These findings suggest that ACEI/ARB therapy may not confer meaningful clinical benefit in the ATTR-CM population and highlight the need for prospective research to clarify optimal medical management in this disease.For image description, please refer to the figure legend and surrounding text.