Causes of Cardiovascular Hospitalization and Death in Patients With Transthyretin Amyloid Cardiomyopathy (from the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial [ATTR-ACT])

Am J Cardiol. 2021 Jun 1;148:146-150. doi: 10.1016/j.amjcard.2021.02.035. Epub 2021 Mar 3.

Abstract

In the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT), tafamidis significantly reduced mortality and cardiovascular (CV)-related hospitalizations compared with placebo in patients with transthyretin amyloid cardiomyopathy (ATTR-CM). This analysis aimed to assess the causes of CV-related death and hospitalization in ATTR-ACT to provide further insight into the progression of ATTR-CM and efficacy of tafamidis. ATTR-ACT was an international, double-blind, placebo-controlled, and randomized study. Patients with hereditary or wild-type ATTR-CM were randomized to tafamidis (n = 264) or placebo (n = 177) for 30 months. The independent Endpoint Adjudication Committee determined whether certain investigator-reported events met the definition of disease-related efficacy endpoints using predefined criteria. Cause-specific reasons for CV-related deaths (heart failure [HF], arrhythmia, myocardial infarction, sudden death, stroke, and other CV causes) and hospitalizations (HF, arrhythmia, myocardial infarction, transient ischemic attack/stroke, and other CV causes) were assessed. Total CV-related deaths was 53 (20.1%) with tafamidis and 50 (28.2%) with placebo, with HF (15.5% tafamidis, 22.6% placebo), followed by sudden death (2.7% tafamidis, 5.1% placebo), the most common causes. The number of patients with a CV-related hospitalization was 138 (52.3%) with tafamidis and 107 (60.5%) with placebo; with HF the most common cause (43.2% tafamidis, 50.3% placebo). All predefined causes of CV-related death or hospitalization were less frequent with tafamidis than placebo. In conclusion, these data provide further insight into CV disease progression in patients with ATTR-CM, with HF the most common adjudicated cause of CV-related hospitalization or death in ATTR-ACT. Clinical trial registration ClinicalTrials.gov: NCT01994889.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Amyloid Neuropathies, Familial / drug therapy*
  • Amyloid Neuropathies, Familial / genetics
  • Amyloidosis / drug therapy
  • Amyloidosis / genetics
  • Arrhythmias, Cardiac / epidemiology
  • Arrhythmias, Cardiac / mortality
  • Benzoxazoles / therapeutic use
  • Cardiomyopathies / drug therapy*
  • Cardiomyopathies / genetics
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / mortality*
  • Cause of Death
  • Death, Sudden, Cardiac / epidemiology
  • Double-Blind Method
  • Female
  • Heart Failure / epidemiology
  • Heart Failure / mortality
  • Hospitalization / statistics & numerical data*
  • Humans
  • Ischemic Attack, Transient / epidemiology
  • Male
  • Myocardial Infarction / epidemiology
  • Myocardial Infarction / mortality
  • Prealbumin / genetics
  • Proportional Hazards Models
  • Stroke / epidemiology
  • Stroke / mortality

Substances

  • Benzoxazoles
  • Prealbumin
  • TTR protein, human
  • tafamidis

Supplementary concepts

  • Amyloidosis, Hereditary, Transthyretin-Related

Associated data

  • ClinicalTrials.gov/NCT01994889