Long-Term Survival With Tafamidis in Patients With Transthyretin Amyloid Cardiomyopathy

Circ Heart Fail. 2022 Jan;15(1):e008193. doi: 10.1161/CIRCHEARTFAILURE.120.008193. Epub 2021 Dec 20.


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.

Keywords: amyloid; cardiomyopathies; heart failure; mutation; phenotype.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Amyloid Neuropathies, Familial / complications
  • Amyloid Neuropathies, Familial / drug therapy*
  • Amyloid Neuropathies, Familial / mortality*
  • Benzoxazoles / pharmacology*
  • Cardiomyopathies / complications
  • Cardiomyopathies / drug therapy
  • Cardiomyopathies / mortality*
  • Female
  • Heart Failure / complications
  • Heart Failure / drug therapy
  • Heart Failure / mortality
  • Hospitalization / statistics & numerical data
  • Humans
  • Male
  • Middle Aged
  • Prealbumin / pharmacology
  • Proportional Hazards Models
  • Time*


  • Benzoxazoles
  • Prealbumin
  • tafamidis

Supplementary concepts

  • Amyloidosis, Hereditary, Transthyretin-Related

Associated data

  • ClinicalTrials.gov/NCT01994889
  • ClinicalTrials.gov/NCT02791230