The Effect of Tafamidis on Vascular and Arrhythmic Events in Cardiac Amyloidosis: A Post-Hoc Analysis of the Transthyretin Amyloidosis Cardiomyopathy Clinical Trial (ATTR-ACT)
Document Type
Conference Proceeding
Publication Date
4-1-2025
Publication Title
Journal of the American College of Cardiology
Abstract
Background: Transthyretin cardiac amyloidosis (aTTR) is characterized by amyloid deposition in the heart, leading to restrictive cardiomyopathy. In the Transthyretin Amyloidosis Cardiomyopathy Clinical Trial (ATTR-ACT), Tafamidis improved heart failure outcomes and mortality by preventing amyloid formation. The objective of this study was to analyze data from this pivotal trial to assess the impact of the transthyretin stabilizer, Tafamidis, on vascular and arrhythmic events. Methods: The ATTR-ACT trial was a multicenter, double-blind, placebo controlled trial. It was analyzed post-hoc using a cox proportional hazards model adjusting for treatment assignment, age, sex and history of coronary artery disease, myocardial infarction, pacemaker, stroke, transient ischemic attack, and atrial fibrillation. This publication is based on data from Pfizer that has been made available through Vivli, Inc. The study was approved by the Corewell Health IRB. Analyses were conducted using SAS v9.4. Results: 441 participants were randomized to Tafamidis (n=264) or placebo (n=177). Tafamidis treatment resulted in fewer adverse vascular and arrhythmic events (MACE) at 29.5% compared to 37.9% with placebo (p=0.02). The most common subcomponents of the combined outcome were cardioversion, occurring in 11.4% and 16.4% of Tafamidis and placebo treatment participants. Atrial fibrillation, occurring in 8.0% and 10.7%; pacemaker implantation in 7.6% and 9.0%; implantable cardioverter defibrillator in 6.1% and 11.3%; syncope in 2.7% and 7.9% and ventricular tachycardia in 1.5% and 5.1%. On multivariate analysis, only treatment with Tafamidis was significantly associated with fewer events with hazard ratio of 0.67 (0.48-0.93). Atrial thrombosis was the most frequent vascular event and occurred in 0.8% and 2.8% of Tafamidis and placebo participants. Cerebrovascular accident, transient ischemic attack and angioplasty all occurred in less than 2% of participants. Conclusion: Tafamidis significantly reduced the combined outcome of first vascular and arrhythmic event, like atrial fibrillation and heart block requiring to device implantation, supporting its use in managing aTTR comorbidities.
Volume
85
Issue
12 Suppl
First Page
1611
Last Page
1611
Recommended Citation
Steafo L, Skaistis J, George J. The effect of tafamidis on vascular and arrhythmic events in cardiac amyloidosis: a post-hoc analysis of the transthyretin amyloidosis cardiomyopathy clinical trial (ATTR-ACT). 2025 Apr 1;85(12 Suppl):1611. doi:10.1016/S0735-1097(25)02095-9
DOI
10.1016/S0735-1097(25)02095-9
Comments
American College of Cardiology (ACC) Meeting, March 29-31, 2025, Chicago, IL