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Clinical Trial
. 2025 Feb 25;85(7):744-752.
doi: 10.1016/j.jacc.2024.10.097. Epub 2025 Jan 22.

Worsening of Heart Failure in Outpatients With Transthyretin Amyloidosis and Cardiomyopathy in the APOLLO-B Trial

Marianna Fontana  1 , Mathew S Maurer  2 , Julian D Gillmore  1 , Shaun Bender  3 , Patrick Y Jay  3 , Scott D Solomon  4
Affiliations
Free article
Clinical Trial

Worsening of Heart Failure in Outpatients With Transthyretin Amyloidosis and Cardiomyopathy in the APOLLO-B Trial

Marianna Fontana et al. J Am Coll Cardiol. .
Free article

Abstract

Background: Outpatient worsening heart failure (HF), defined by initiation or intensification of diuretics, is adversely prognostic for patients with either reduced or preserved ejection fraction.

Objectives: This study sought to investigate the prognostic value of outpatient worsening HF in transthyretin amyloidosis with cardiomyopathy and the effect of patisiran treatment.

Methods: Post hoc analyses of the APOLLO-B trial (NCT03997383) evaluated the associations between outpatient worsening HF (defined by oral diuretic initiation or intensification), measures of disease progression, and a composite endpoint of all-cause mortality and cardiovascular (CV) events. We further examined the effect of patisiran on outpatient worsening HF over 24 months (ie, during the double-blind and open-label extension periods).

Results: In APOLLO-B, 144 (40.1%) patients had no event, 157 (43.7%) had outpatient worsening HF, 13 (3.6%) required an urgent HF visit, 118 (32.9%) had a CV hospitalization, and 47 (13.1%) died. Outpatient worsening HF was associated with an increased risk of all-cause mortality and CV events (HR: 2.21; 95% CI: 1.58-3.08), as well as a greater deterioration in 6-minute walk test distance, Kansas City Cardiomyopathy Questionnaire-Overall Summary score, and NYHA functional class and a greater increase in N-terminal prohormone of B-type natriuretic peptide. Addition of outpatient diuretic initiation or intensification to the composite endpoint of all-cause mortality and CV events increased the overall number of patients having an event from 141 to 215 (a 52% increase). Patisiran reduced the risk of outpatient worsening HF (HR: 0.70; 95% CI: 0.51-0.96) over 24 months.

Conclusions: During APOLLO-B, outpatient worsening HF in patients with transthyretin amyloidosis with cardiomyopathy was frequent, prognostic, and reduced by patisiran.

Keywords: RNAi; diuretic; heart failure; transthyretin amyloidosis.

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Conflict of interest statement

Funding Support and Author Disclosures This study was funded by Alnylam Pharmaceuticals Inc. The funder collaborated with the authors during the study design, data collection, data analysis, data interpretation, and writing of the report. Dr Fontana has received research support from AstraZeneca; has performed consultancy and/or held Advisory Board membership for Alexion, Alnylam Pharmaceuticals, Attralus, Caelum Biosciences, Intellia Therapeutics, Ionis Pharmaceuticals, Janssen Pharmaceuticals, Lexeo Therapeutics, Novo Nordisk, Pfizer, and Prothena; has received support for attending meetings from Alnylam Pharmaceuticals, AstraZeneca, and Attralus; and owns equity in Lexeo Therapeutics and Mycardium. Dr Maurer has received grant support from the National Institutes of Health (R01HL139671 and AG081582); has received grants from Alnylam Pharmaceuticals, BridgeBio, Intellia Therapeutics, and Ionis Pharmaceuticals; and has received personal fees from Akcea, Alnylam Pharmaceuticals, AstraZeneca, Intellia Therapeutics, Novo Nordisk, Prothena, and Roche. Dr Gillmore has received research support from Alnylam Pharmaceuticals; has received consulting fees from Alnylam Pharmaceuticals, AstraZeneca, BridgeBio, Intellia Therapeutics, Ionis Pharmaceuticals, and Lycia Therapeutics; and has received payment for lectures or speaker fees from Alnylam Pharmaceuticals and AstraZeneca. Drs Bender and Jay are employees of and own equity in Alnylam Pharmaceuticals. Dr Solomon has received research grants from Alexion, Alnylam Pharmaceuticals, Applied Therapeutics, AstraZeneca, Bayer, Bellerophon, Boston Scientific, Bristol Myers Squibb, Cytokinetics, Edgewise, Eidos/Bridgebio, Gossamer, GlaxoSmithKline, Ionis Pharmaceuticals, Lilly, the National Institutes of Health/National Heart, Lung, and Blood Institute, Novartis, Novo Nordisk, Respicardia, Sanofi Pasteur, Tenaya, Theracos, and US2.AI; and has consulted for Abbott, Action, Akros, Alexion, Alnylam Pharmaceuticals, American Regent, Amgen, Anacardio, Arena, AstraZeneca, Bayer, Bristol Myers Squibb, Cardior, Cardurion, CellProThera, Corvia, Cytokinetics, Dinaqor, GlaxoSmithKline, Lexicon, Lilly, Moderna, Novartis, Quantum Genomics, Roche, Sanofi Pasteur, Sarepta, Tenaya, Theracos, Tremeau, and Valo.

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