Treatment With Tafamidis Slows Disease Progression in Early-Stage Transthyretin Cardiomyopathy

Marla B Sultan, Balarama Gundapaneni, Jennifer Schumacher, Jeffrey H Schwartz, Marla B Sultan, Balarama Gundapaneni, Jennifer Schumacher, Jeffrey H Schwartz

Abstract

Background: Transthyretin cardiomyopathy (TTR-CM) is a progressive, fatal disease caused by the accumulation of misfolded transthyretin (TTR) amyloid fibrils in the heart. Tafamidis is a kinetic stabilizer of TTR that inhibits misfolding and amyloid formation.

Methods: In this post hoc analysis, data from an observational study (Transthyretin Amyloidosis Cardiac Study; n = 29) were compared with an open-label study of tafamidis in patients with TTR-CM (Fx1B-201; n = 35). To ensure comparable baseline disease severity, patients with New York Heart Association (NYHA) functional classification ≥III were excluded in this time-to-mortality analysis.

Results: Patients with either wild-type or Val122Ile genotypes treated with tafamidis have a significantly longer time to death compared with untreated patients (P = .0004). Similar results were obtained when limiting the analysis to wild-type patients only, without restricting NYHA functional classification (P = .0262).

Conclusions: These results support earlier conclusions suggesting that tafamidis slows disease progression compared with no treatment outside of standard of care and warrant further investigation.

Trial registration: ClinicalTrials.gov, NCT00694161.

Keywords: Transthyretin; cardiac amyloidosis; heart failure; tafamidis.

Conflict of interest statement

Declaration of conflicting interests:The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: M.B.S., J.S., and J.H.S. are full-time employees of Pfizer and hold stock and/or stock options. B.G. is a full-time employee of inVentiv Health, a paid contractor to Pfizer for statistical analysis and development of this manuscript.

Figures

Figure 1.
Figure 1.
Time to mortality from diagnosis date for patients with NYHA functional classification I or II. NYHA, New York Heart Association; TRACS, Transthyretin Amyloidosis Cardiac Study.
Figure 2.
Figure 2.
Time to mortality from diagnosis date for patients with wild-type transthyretin. TRACS, Transthyretin Amyloidosis Cardiac Study.

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