dc.contributor.author | Damy, Thibaud | |
dc.contributor.author | García Pavía, Pablo | |
dc.contributor.author | Hanna, Mazen | |
dc.contributor.author | Judge, Daniel P. | |
dc.contributor.author | Merlini, Giampaolo | |
dc.contributor.author | Gundapaneni, Balarama | |
dc.contributor.author | Patterson, Terrell A. | |
dc.contributor.author | Riley, Steven | |
dc.contributor.author | Schwartz, Jeffrey H. | |
dc.contributor.author | Sultan, Marla B. | |
dc.contributor.author | Witteles, Ronald | |
dc.date.accessioned | 2021-01-13T14:24:21Z | |
dc.date.available | 2021-01-13T14:24:21Z | |
dc.date.issued | 2020 | |
dc.identifier.issn | 1388-9842 | spa |
dc.identifier.uri | http://hdl.handle.net/10641/2158 | |
dc.description.abstract | Aims Tafamidis is an effective treatment for transthyretin amyloid cardiomyopathy (ATTR-CM) in the Tafamidis in
Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT). While ATTR-ACT was not designed for a dose-specific
assessment, further analysis from ATTR-ACT and its long-term extension study (LTE) can guide determination of the
optimal dose.
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Methods
and results
In ATTR-ACT, patients were randomized (2:1:2) to tafamidis 80 mg, 20mg, or placebo for 30months. Patients
completing ATTR-ACT could enrol in the LTE (with placebo-treated patients randomized to tafamidis 80 or
20 mg; 2:1) and all patients were subsequently switched to high-dose tafamidis. All-cause mortality was assessed
in ATTR-ACT combined with the LTE (median follow-up 51 months). In ATTR-ACT, the combination of all-cause
mortality and cardiovascular-related hospitalizations over 30 months was significantly reduced with tafamidis 80mg
(P = 0.0030) and 20mg (P = 0.0048) vs. placebo. All-cause mortality vs. placebo was reduced with tafamidis 80mg
[Cox hazards model (95% confidence interval (CI): 0.690 (0.487–0.979), P = 0.0378] and 20mg [0.715 (0.450–1.137),
P = 0.1564]. The mean (standard error) change in N-terminal pro-B-type natriuretic peptide from baseline to Month
30 was −1170.51 (587.31) (P = 0.0468) with tafamidis 80 vs. 20 mg. In ATTR-ACT combined with the LTE there
was a significantly greater survival benefit with tafamidis 80 vs. 20 mg [0.700 (0.501–0.979), P = 0.0374]. Incidence
of adverse events in both tafamidis doses were comparable to placebo.
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Conclusion Tafamidis, both 80 and 20mg, effectively reduced mortality and cardiovascular-related hospitalizations in patients
with ATTR-CM. The longer-term survival data and the lack of dose-related safety concerns support tafamidis 80mg
as the optimal dose.
Clinical Trial Registration: ClinicalTrials.gov NCT01994889; NCT02791230 | spa |
dc.language.iso | eng | spa |
dc.publisher | European Journal of Heart Failure | spa |
dc.rights | Atribución-NoComercial-SinDerivadas 3.0 España | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/es/ | * |
dc.subject | Transthyretin amyloid cardiomyopathy | spa |
dc.subject | Clinical trial | spa |
dc.subject | Biomarkers | spa |
dc.subject | Mortality | spa |
dc.title | Efficacy and safety of tafamidis doses in the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT) and long-term extension study. | spa |
dc.type | journal article | spa |
dc.type.hasVersion | AM | spa |
dc.rights.accessRights | open access | spa |
dc.description.extent | 369 KB | spa |
dc.identifier.doi | 10.1002/ejhf.2027 | spa |
dc.relation.publisherversion | https://onlinelibrary.wiley.com/doi/10.1002/ejhf.2027 | spa |