Physicians' Academy for Cardiovascular Education

Transthyretin stabilizer increases serum transthyretin levels

Effect of Tafamidis on Serum Transthyretin Levels in Non-Trial Patients With Transthyretin Amyloid Cardiomyopathy

Literature - Falk RH, Haddad M, Walker CR et al., - J Am Coll Cardiol CardioOnc 2021;3:580-586,

In a study of non-trial patients with transthyretin (TTR) amyloid cardiomyopathy, treatment with tafamidis increases serum TTR by 34.5% after a follow-up of 21 weeks.

Introduction and methods


The stabilizing drug tafamidis binds to the transthyretin (TTR) tetramer and inhibits its dissociation into monomers. This results in the inhibition of amyloid formation in susceptible patients [1,2]. The ATTR-ACT trial demonstrated that tafamidis slowed the progression of amyloid cardiomyopathy with less 30-month hospitalization for HF and reduced mortality compared to placebo [3], but did not completely stop the progression of the disease. This may be due to a reduced stabilization of the TTR molecule by tafamidis. It has been hypothesized that a greater drug-induced TTR stability may improve outcomes.

In this study, the effect of tafamidis meglumine 80 mg or tafamidis 61 mg on TTR levels was examined in an unselected group of patients with amyloid cardiomyopathy. Due to lack of a current marker to determine the efficacy of tafamidis, measurement of TTR levels before and after treatment may be a surrogate for TTR stabilization.

Study design

TTR levels were measured before therapy and 3 to 12 months after initiation of tafamidis therapy in 72 patients with transthyretin amyloidosis (ATTR) who were seen at the Brigham and Women’s Hospital Amyloidosis Program in Boston, MA, USA from May 20, 2019 until March 1, 2021.


Changes in TTR levels, as well as changes in NT-proBNP and high-sensitivity troponin T.

Main results


Tafamidis therapy resulted in consistently increased TTR levels in an unselected group of patients with ATTR cardiomyopathy.

It is still unknown whether greater stability of TTR than that achieved by tafamidis will improve clinical outcomes. But measurement of TTR levels may offer reassurance to the patients and clinicians that tafamidis is effective in its desired biochemical effect of stabilization.


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Find this article online at JACC CardioOnc

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