PMID- 35853436
OWN - NLM
STAT- MEDLINE
DCOM- 20221019
LR  - 20221205
IS  - 1421-9751 (Electronic)
IS  - 0008-6312 (Linking)
VI  - 147
IP  - 4
DP  - 2022
TI  - Estimating the Effect of Tafamidis on Cardiovascular-Related Hospitalization in 
      NYHA Class III Patients with Transthyretin Amyloid Cardiomyopathy in the Presence 
      of Death.
PG  - 398-405
LID - 10.1159/000525883 [doi]
AB  - BACKGROUND: The Tafamidis in Transthyretin Cardiomyopathy Clinical Trial 
      (ATTR-ACT) demonstrated the effectiveness of tafamidis for the treatment of 
      patients with transthyretin amyloid cardiomyopathy (ATTR-CM). Tafamidis reduced 
      mortality in all subgroups of patients studied. Tafamidis also reduced observed 
      frequency of cardiovascular (CV)-related hospitalizations in all subgroups except 
      those who were New York Heart Association (NYHA) class III at baseline who, 
      paradoxically, had a higher frequency of CV-related hospitalizations than 
      placebo. Given the greater mortality rate with placebo, this analysis assessed 
      the impact of the confounding effect of death on the frequency of CV-related 
      hospitalization in ATTR-ACT. METHODS: In ATTR-ACT, patients with ATTR-CM were 
      randomized to tafamidis (n = 264) or placebo (n = 177) for 30 months. Post hoc 
      analyses first defined and compared the effect of tafamidis treatment in the 
      subset of NYHA class III patients from each treatment arm alive at month 30. The 
      impact of a potential survivor bias was then adjusted for using principal 
      stratification, estimating the frequency of CV-related hospitalization in NYHA 
      class III patients who would have survived regardless of assigned treatment group 
      (defined as the survivor average causal effect [SACE]). RESULTS: In the subset of 
      NYHA class III patients alive at month 30, tafamidis reduced the relative risk of 
      CV-related hospitalization versus placebo (relative risk: 0.95 [95% CI: 
      0.55-1.65]). In the principal stratification analyses of those patients who would 
      survive to 30 months regardless of treatment, tafamidis treatment was associated 
      with a 24% lower risk of CV-related hospitalization (relative risk: 0.76 [95% CI: 
      0.45-1.24]). Similarly, there was a larger reduction in CV-related 
      hospitalization frequency with tafamidis in NYHA class I or II patients in the 
      SACE than was initially observed in ATTR-ACT. CONCLUSIONS: Initial data from 
      ATTR-ACT likely underestimated the effect of tafamidis on CV-related 
      hospitalizations due to the confounding effect of death. When SACE was used to 
      adjust for survivor bias, there was a 24% reduction in the frequency of 
      CV-related hospitalization in NYHA class III patients treated with tafamidis.
CI  - (c) 2022 The Author(s). Published by S. Karger AG, Basel.
FAU - Li, Huihua
AU  - Li H
AD  - Pfizer Inc, Collegeville, Pennsylvania, USA.
FAU - Rozenbaum, Mark
AU  - Rozenbaum M
AD  - Pfizer Inc, Capelle aan den IJssel, The Netherlands.
FAU - Casey, Michelle
AU  - Casey M
AD  - Pfizer Inc, Collegeville, Pennsylvania, USA.
FAU - Sultan, Marla B
AU  - Sultan MB
AD  - Pfizer Inc, New York, New York, USA.
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20220719
PL  - Switzerland
TA  - Cardiology
JT  - Cardiology
JID - 1266406
RN  - 0 (Benzoxazoles)
RN  - 0 (Prealbumin)
RN  - 8FG9H9D31J (tafamidis)
SB  - IM
MH  - *Amyloid Neuropathies, Familial/complications/drug therapy
MH  - Benzoxazoles
MH  - *Cardiomyopathies/complications/drug therapy
MH  - Hospitalization
MH  - Humans
MH  - Prealbumin
OTO - NOTNLM
OT  - Hospitalizations
OT  - Principal stratification
OT  - Survivor average causal effect
OT  - Transthyretin amyloid cardiomyopathy
EDAT- 2022/07/20 06:00
MHDA- 2022/10/20 06:00
CRDT- 2022/07/19 18:28
PHST- 2021/11/29 00:00 [received]
PHST- 2022/06/20 00:00 [accepted]
PHST- 2022/07/20 06:00 [pubmed]
PHST- 2022/10/20 06:00 [medline]
PHST- 2022/07/19 18:28 [entrez]
AID - 000525883 [pii]
AID - 10.1159/000525883 [doi]
PST - ppublish
SO  - Cardiology. 2022;147(4):398-405. doi: 10.1159/000525883. Epub 2022 Jul 19.