PMID- 33770392
OWN - NLM
STAT- MEDLINE
DCOM- 20211222
LR  - 20220218
IS  - 1179-187X (Electronic)
IS  - 1175-3277 (Print)
IS  - 1175-3277 (Linking)
VI  - 21
IP  - 5
DP  - 2021 Sep
TI  - Modeling of Survival and Frequency of Cardiovascular-Related Hospitalization in 
      Patients with Transthyretin Amyloid Cardiomyopathy Treated with Tafamidis.
PG  - 535-543
LID - 10.1007/s40256-021-00464-y [doi]
AB  - INTRODUCTION: ATTR-ACT (Tafamidis in Transthyretin Cardiomyopathy Clinical Trial) 
      demonstrated the efficacy and safety of tafamidis in transthyretin amyloid 
      cardiomyopathy (ATTR-CM). Model-based analyses from ATTR-ACT can examine 
      predictor effects on dose-response/exposure-response relationships. METHODS: 
      Parametric hazard distributions were developed for all-cause mortality and 
      frequency of cardiovascular-related hospitalization. Time-to-event models were 
      fitted to survival data, and repeated time-to-event models were fitted to 
      hospitalization data. Disease-specific characteristics were assessed as baseline 
      predictors of event hazards. RESULTS: There were 441 patients in this analysis. 
      At month 30, 70.5% (tafamidis) and 57.1% (placebo) of patients were alive, with 
      154/441 deaths reported; 495 cardiovascular-related hospitalizations occurred. 
      The cumulative risk of death was 42.1% (95% confidence interval [CI] 24.2-58.0) 
      lower with tafamidis than with placebo, regardless of New York Heart Association 
      (NYHA) class; significant predictors of decreased risk were genotype (wild-type), 
      greater 6-Minute Walk Test (6MWT) distance, higher left ventricular ejection 
      fraction (LVEF), and lower blood urea nitrogen (BUN) and N-terminal pro-B-type 
      natriuretic peptide concentrations. The average cumulative risk of 
      cardiovascular-related hospitalization up to 30 months was 40.8% (95% CI 
      31.0-49.7) lower with tafamidis in NYHA class I/II patients. Significant 
      predictors of reduced risk were greater 6MWT distance, higher LVEF, and lower BUN 
      and troponin I concentrations. CONCLUSIONS: Tafamidis reduced cumulative 
      mortality and hospitalization risk versus placebo in patients with ATTR-CM. 
      Baseline predictors of outcome were consistent with the cardiovascular nature of 
      the disease and suggested that earlier treatment may improve outcomes. CLINICAL 
      TRIALS. GOV IDENTIFIER: NCT01994889 (date of registration: November 26, 2013).
CI  - (c) 2021. The Author(s).
FAU - Vong, Camille
AU  - Vong C
AD  - Clinical Pharmacology, Pharmacometrics, Pfizer Inc, Cambridge, MA, USA.
FAU - Boucher, Martin
AU  - Boucher M
AD  - Clinical Pharmacology, Pharmacometrics, Pfizer Inc, Sandwich, UK.
FAU - Riley, Steve
AU  - Riley S
AD  - Clinical Pharmacology, Pfizer Inc, Groton, CT, USA.
FAU - Harnisch, Lutz O
AU  - Harnisch LO
AUID- ORCID: 0000-0002-4085-1577
AD  - Clinical Pharmacology, Pharmacometrics, Pfizer Inc, Sandwich, UK. 
      Lutz.O.Harnisch@pfizer.com.
LA  - eng
SI  - ClinicalTrials.gov/NCT01994889
PT  - Journal Article
DEP - 20210326
PL  - New Zealand
TA  - Am J Cardiovasc Drugs
JT  - American journal of cardiovascular drugs : drugs, devices, and other 
      interventions
JID - 100967755
RN  - 0 (Benzoxazoles)
RN  - 8FG9H9D31J (tafamidis)
SB  - IM
MH  - *Amyloid Neuropathies, Familial/drug therapy
MH  - *Benzoxazoles/therapeutic use
MH  - *Cardiomyopathies/drug therapy
MH  - Hospitalization/statistics & numerical data
MH  - Humans
MH  - Models, Statistical
MH  - Survival Analysis
PMC - PMC8435516
COIS- S. Riley, M. Boucher, and L.O. Harnisch are full-time employees of, and hold 
      stock and/or stock options with, Pfizer. C. Vong was a full-time employee of 
      Pfizer at the time of the analysis; she is now a full-time employee of Novartis 
      AG and holds stock options with Novartis AG.
EDAT- 2021/03/27 06:00
MHDA- 2021/12/24 06:00
PMCR- 2021/03/26
CRDT- 2021/03/26 17:34
PHST- 2021/01/19 00:00 [accepted]
PHST- 2021/03/27 06:00 [pubmed]
PHST- 2021/12/24 06:00 [medline]
PHST- 2021/03/26 17:34 [entrez]
PHST- 2021/03/26 00:00 [pmc-release]
AID - 10.1007/s40256-021-00464-y [pii]
AID - 464 [pii]
AID - 10.1007/s40256-021-00464-y [doi]
PST - ppublish
SO  - Am J Cardiovasc Drugs. 2021 Sep;21(5):535-543. doi: 10.1007/s40256-021-00464-y. 
      Epub 2021 Mar 26.