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Long-Term Survival With Tafamidis in Patients With Transthyretin Amyloid Cardiomyopathy
BACKGROUND: Tafamidis is approved in many countries for the treatment of transthyretin amyloid cardiomyopathy. This study reports data on the long-term efficacy of tafamidis from an ongoing long-term extension (LTE) to the pivotal ATTR-ACT (Tafamidis in Transthyretin Cardiomyopathy Clinical Trial)....
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Lippincott Williams & Wilkins
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8763250/ https://www.ncbi.nlm.nih.gov/pubmed/34923848 http://dx.doi.org/10.1161/CIRCHEARTFAILURE.120.008193 |
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author | Elliott, Perry Drachman, Brian M. Gottlieb, Stephen S. Hoffman, James E. Hummel, Scott L. Lenihan, Daniel J. Ebede, Ben Gundapaneni, Balarama Li, Benjamin Sultan, Marla B. Shah, Sanjiv J. |
author_facet | Elliott, Perry Drachman, Brian M. Gottlieb, Stephen S. Hoffman, James E. Hummel, Scott L. Lenihan, Daniel J. Ebede, Ben Gundapaneni, Balarama Li, Benjamin Sultan, Marla B. Shah, Sanjiv J. |
author_sort | Elliott, Perry |
collection | PubMed |
description | BACKGROUND: Tafamidis is approved in many countries for the treatment of transthyretin amyloid cardiomyopathy. This study reports data on the long-term efficacy of tafamidis from an ongoing long-term extension (LTE) to the pivotal ATTR-ACT (Tafamidis in Transthyretin Cardiomyopathy Clinical Trial). METHODS: Patients with transthyretin amyloid cardiomyopathy who completed ATTR-ACT could enroll in an LTE, continuing with the same tafamidis dose or, if previously treated with placebo, randomized (2:1) to tafamidis meglumine 80 or 20 mg. All patients in the LTE transitioned to tafamidis free acid 61 mg (bioequivalent to tafamidis meglumine 80 mg) following a protocol amendment. In this interim analysis, all-cause mortality was assessed in patients treated with tafamidis meglumine 80 mg in ATTR-ACT continuing in the LTE, compared with those receiving placebo in ATTR-ACT transitioning to tafamidis in the LTE. RESULTS: Median follow-up was 58.5 months in the continuous tafamidis group (n=176) and 57.1 months in the placebo to tafamidis group (n=177). There were 79 (44.9%) deaths with continuous tafamidis and 111 (62.7%) with placebo to tafamidis (hazard ratio, 0.59 [95% CI, 0.44–0.79]; P<0.001). Mortality was also reduced in the continuous tafamidis (versus placebo to tafamidis) subgroups of: variant transthyretin amyloidosis (0.57 [0.33–0.99]; P=0.05) and wild-type transthyretin amyloidosis (0.61 [0.43–0.87]; P=0.006); and baseline New York Heart Association class I and II (0.56 [0.38–0.82]; P=0.003) and class III (0.65 [0.41–1.01]; P=0.06). CONCLUSIONS: In the LTE, patients initially treated with tafamidis in ATTR-ACT had substantially better survival than those first treated with placebo, highlighting the importance of early diagnosis and treatment in transthyretin amyloid cardiomyopathy. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01994889 and NCT02791230. |
format | Online Article Text |
id | pubmed-8763250 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Lippincott Williams & Wilkins |
record_format | MEDLINE/PubMed |
spelling | pubmed-87632502022-01-21 Long-Term Survival With Tafamidis in Patients With Transthyretin Amyloid Cardiomyopathy Elliott, Perry Drachman, Brian M. Gottlieb, Stephen S. Hoffman, James E. Hummel, Scott L. Lenihan, Daniel J. Ebede, Ben Gundapaneni, Balarama Li, Benjamin Sultan, Marla B. Shah, Sanjiv J. Circ Heart Fail Original Articles BACKGROUND: Tafamidis is approved in many countries for the treatment of transthyretin amyloid cardiomyopathy. This study reports data on the long-term efficacy of tafamidis from an ongoing long-term extension (LTE) to the pivotal ATTR-ACT (Tafamidis in Transthyretin Cardiomyopathy Clinical Trial). METHODS: Patients with transthyretin amyloid cardiomyopathy who completed ATTR-ACT could enroll in an LTE, continuing with the same tafamidis dose or, if previously treated with placebo, randomized (2:1) to tafamidis meglumine 80 or 20 mg. All patients in the LTE transitioned to tafamidis free acid 61 mg (bioequivalent to tafamidis meglumine 80 mg) following a protocol amendment. In this interim analysis, all-cause mortality was assessed in patients treated with tafamidis meglumine 80 mg in ATTR-ACT continuing in the LTE, compared with those receiving placebo in ATTR-ACT transitioning to tafamidis in the LTE. RESULTS: Median follow-up was 58.5 months in the continuous tafamidis group (n=176) and 57.1 months in the placebo to tafamidis group (n=177). There were 79 (44.9%) deaths with continuous tafamidis and 111 (62.7%) with placebo to tafamidis (hazard ratio, 0.59 [95% CI, 0.44–0.79]; P<0.001). Mortality was also reduced in the continuous tafamidis (versus placebo to tafamidis) subgroups of: variant transthyretin amyloidosis (0.57 [0.33–0.99]; P=0.05) and wild-type transthyretin amyloidosis (0.61 [0.43–0.87]; P=0.006); and baseline New York Heart Association class I and II (0.56 [0.38–0.82]; P=0.003) and class III (0.65 [0.41–1.01]; P=0.06). CONCLUSIONS: In the LTE, patients initially treated with tafamidis in ATTR-ACT had substantially better survival than those first treated with placebo, highlighting the importance of early diagnosis and treatment in transthyretin amyloid cardiomyopathy. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01994889 and NCT02791230. Lippincott Williams & Wilkins 2021-12-20 /pmc/articles/PMC8763250/ /pubmed/34923848 http://dx.doi.org/10.1161/CIRCHEARTFAILURE.120.008193 Text en © 2021 The Authors. https://creativecommons.org/licenses/by-nc-nd/4.0/Circulation: Heart Failure is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial-NoDerivs (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited, the use is noncommercial, and no modifications or adaptations are made. |
spellingShingle | Original Articles Elliott, Perry Drachman, Brian M. Gottlieb, Stephen S. Hoffman, James E. Hummel, Scott L. Lenihan, Daniel J. Ebede, Ben Gundapaneni, Balarama Li, Benjamin Sultan, Marla B. Shah, Sanjiv J. Long-Term Survival With Tafamidis in Patients With Transthyretin Amyloid Cardiomyopathy |
title | Long-Term Survival With Tafamidis in Patients With Transthyretin Amyloid Cardiomyopathy |
title_full | Long-Term Survival With Tafamidis in Patients With Transthyretin Amyloid Cardiomyopathy |
title_fullStr | Long-Term Survival With Tafamidis in Patients With Transthyretin Amyloid Cardiomyopathy |
title_full_unstemmed | Long-Term Survival With Tafamidis in Patients With Transthyretin Amyloid Cardiomyopathy |
title_short | Long-Term Survival With Tafamidis in Patients With Transthyretin Amyloid Cardiomyopathy |
title_sort | long-term survival with tafamidis in patients with transthyretin amyloid cardiomyopathy |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8763250/ https://www.ncbi.nlm.nih.gov/pubmed/34923848 http://dx.doi.org/10.1161/CIRCHEARTFAILURE.120.008193 |
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