Long-Term Survival With Tafamidis in PatientsWith Transthyretin Amyloid Cardiomyopathy

Perry Elliott , MD; Brian M. Drachman, MD; Stephen S. Gottlieb , MD; James E. Hoffman, MD; Scott L. Hummel , MD;
Daniel J. Lenihan , MD; Ben Ebede, MS, MBA; Balarama Gundapaneni, MS; Benjamin Li, MS; Marla B. Sultan, MD, MBA;
Sanjiv J. Shah , MD
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