Elsevier

JACC: Heart Failure

Volume 9, Issue 2, February 2021, Pages 115-123
JACC: Heart Failure

Focus Issue: Mechanistic Insights and Drug Therapy
Original Research
Efficacy of Tafamidis in Patients With Hereditary and Wild-Type Transthyretin Amyloid Cardiomyopathy: Further Analyses From ATTR-ACT

https://doi.org/10.1016/j.jchf.2020.09.011Get rights and content
Under a Creative Commons license
open access

Abstract

Objectives

Tafamidis is an effective treatment for transthyretin amyloid cardiomyopathy (ATTR-CM), this study aimed to determine whether there is a differential effect between variant transthyretin amyloidosis (ATTRv) and wild-type transthyretin (ATTRwt).

Background

ATTR-CM is a progressive, fatal disorder resulting from mutations in the ATTRv or the deposition of denatured ATTRwt.

Methods

In pre-specified analyses from ATTR-ACT (Tafamidis in Transthyretin Cardiomyopathy Clinical Trial), baseline characteristics, all-cause mortality, and change from baseline to month 30 in 6-min walk test distance and Kansas City Cardiomyopathy Questionnaire Overall Summary score were compared in patients with ATTRwt and ATTRv.

Results

There were 335 patients with ATTRwt (201 tafamidis, 134 placebo) and 106 with ATTRv (63 tafamidis, 43 placebo) enrolled in ATTR-ACT. Patients with ATTRwt (vs. ATTRv) had less advanced disease at baseline and a lower rate of disease progression over the study. The reduction in all-cause mortality with tafamidis compared with placebo was not different between ATTRwt (hazard ratio: 0.706 [95% confidence interval (CI): 0.474 to 1.052]; p = 0.0875) and ATTRv (hazard ratio: 0.690 [95% CI: 0.408 to 1.167]; p = 0.1667). Tafamidis was associated with a similar reduction (vs. placebo) in the decline in 6-min walk test distance in ATTRwt (mean ± SE difference from placebo, 77.14 ± 10.78; p < 0.0001) and ATTRv (79.61 ± 29.83 m; p = 0.008); and Kansas City Cardiomyopathy Questionnaire Overall Summary score in ATTRwt (12.72 ± 2.10; p < 0.0001) and ATTRv (18.18 ± 7.75; p = 0.019).

Conclusions

Pre-specified analyses from ATTR-ACT confirm the poor prognosis of untreated ATTRv-related cardiomyopathy compared with ATTRwt, but show the reduction in mortality and functional decline with tafamidis treatment is similar in both disease subtypes. (Safety and Efficacy of Tafamidis in Patients With Transthyretin Cardiomyopathy [ATTR-ACT]; NCT01994889)

Key Words

clinical trial
hereditary
tafamidis
transthyretin amyloid cardiomyopathy
wild-type

Abbreviations and Acronyms

6MWT
6-min walk test
ATTR-CM
transthyretin amyloid cardiomyopathy
ATTRv
variant transthyretin amyloidosis
ATTRwt
wild-type transthyretin amyloidosis
CI
confidence interval
KCCQ-OS
Kansas City Cardiomyopathy Questionnaire Overall Summary
NT-proBNP
N-terminal pro–B-type natriuretic peptide
NYHA
New York Heart Association
TTR
transthyretin

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