Efficacy and Safety of ACEi, ARB, and ARNi in Cardiac Amyloidosis: A Retrospective Propensity Score-Matched Cohort Study.

INTRODUCTION: Angiotensin-converting enzyme inhibitor (ACEi), angiotensin receptor blocker (ARB), and angiotensin receptor-neprilysin inhibitor (ARNi) improve outcomes in non-amyloid heart failure populations; however, their role in cardiac amyloidosis (CA) remains uncertain. METHODS: We conducted a retrospective cohort study using the TriNetX Research Network including patients with CA. Patients receiving ACEi/ARB/ARNi were compared with those not receiving these therapies. Propensity score matching (1:1) was performed. Outcomes included all-cause mortality, hypotension, acute kidney injury (AKI), hyperkalemia, dizziness, and hospitalization over 3 years. Subgroup analyses were performed by sex, left ventricular ejection fraction (LVEF ≤40% vs >40%), and amyloidosis subtype. RESULTS: Among 5,134 patients, 1,692 (33.0%) received ACEi/ARB/ARNi. After matching, 1,447 patients remained in each group. Treatment was associated with lower all-cause mortality (HR, 0.64; p<0.001) but higher hospitalization (HR, 1.32; p<0.001). Risks of hypotension were similar, whereas AKI, hyperkalemia, and dizziness were higher with treatment. Findings were consistent across sex. Mortality reduction persisted in patients with LVEF >40% (HR 0.63, p < 0.001) and showed a similar non-significant trend in those with LVEF ≤40% (HR 0.58, p=0.058). A survival benefit was observed in AL amyloidosis (HR, 0.57; p <0.001) but not in ATTR amyloidosis (HR, 0.78; p=0.122). CONCLUSIONS: In selected patients with AL CA, treatment with ACEi/ARB/ARNi is associated with lower mortality; this association was not observed in patients with ATTR amyloidosis. Therapy was associated with a higher risk of side effects and hospitalizations. Randomized trials are needed to clarify the role of RAAS inhibition in CA.