Publication
Tafamidis treatment for patients with transthyretin amyloid cardiomyopathy
[Aug-2018] ATTR-ACT phase 3 study evaluating tafamidis vs placebo in patients with transthyretin amyloid cardiomyopathy.
What is it about?
Transthyretin amyloid cardiomyopathy (ATTR CM) is a progressive and life threatening condition caused by the deposition of misfolded transthyretin protein in the heart. Prior to disease-modifying therapies, management primarily focused on supportive care, with transplant considered for selected patients.¹
The Transthyretin Amyloidosis Cardiomyopathy Clinical Trial (ATTR ACT; NCT01994889) was a global, randomized, placebo controlled Phase 3 study designed to evaluate whether tafamidis, a transthyretin stabilizer, could improve outcomes in patients with wild type or hereditary ATTR CM.¹
ATTR-ACT evaluated all-cause mortality, cardiovascular-related hospitalizations, functional capacity, and health-related quality of life over 30 months and demonstrated significant reductions in mortality and hospitalization alongside slower decline in function and quality of life with tafamidis versus placebo.¹
Patients who completed ATTR-ACT were eligible to enroll in a long-term extension study (NCT02791230) that enabled assessment of longer-term outcomes and safety.² Subsequent analyses evaluated outcomes according to disease severity, tafamidis dose, cardiac and renal function, atrial fibrillation status, and causes of hospitalization and death.²⁻⁶
Together, these publications provide a comprehensive evidence base describing the efficacy, safety, and long-term clinical outcomes of tafamidis across a broad spectrum of patients with ATTR-CM.
Why is it important?
ATTR-CM is frequently underdiagnosed and is associated with high morbidity and mortality.¹ ATTR-ACT was the first Phase 3 randomized trial to demonstrate that a disease-modifying therapy could significantly improve outcomes in ATTR-CM, including reductions in all-cause mortality and cardiovascular-related hospitalizations versus placebo.¹
The trial used a hierarchical endpoint incorporating all-cause mortality and frequency of cardiovascular-related hospitalizations.¹ Functional capacity and health-related quality-of-life outcomes were assessed alongside survival and hospitalization endpoints.¹
Long-term extension and subgroup analyses demonstrated sustained survival benefit and longer-term preservation of health-related quality of life with tafamidis, while providing additional insight into outcomes across clinically relevant patient subgroups. Across ATTR-ACT and long-term extension analyses, adverse event rates were generally comparable between tafamidis and placebo groups, with no new safety signals identified during longer-term follow-up.²
Key takeaways
- Tafamidis significantly reduced all-cause mortality and cardiovascular-related hospitalisations compared with placebo in patients with ATTR-CM.
- Clinical benefit was observed across both wild-type and hereditary ATTR-CM and across a range of disease severities and patient subtypes.
- Long-term follow-up supported sustained clinical benefit, while analyses across the ATTR-ACT programme demonstrated generally comparable adverse event rates versus placebo and highlighted the potential value of earlier and continuous tafamidis treatment.
References
- Maurer MS, Schwartz JH, Gundapaneni B, Elliott PM, Merlini G, Waddington-Cruz M, et al. Tafamidis Treatment for Patients with Transthyretin Amyloid Cardiomyopathy. N Engl J Med. 2018;379(11):1007-1016. doi:10.1056/NEJMoa1805689.
- Damy T, Garcia-Pavia P, Hanna M, Judge DP, Merlini G, Gundapaneni B, et al. Efficacy and safety of tafamidis doses in the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT) and long-term extension study. Eur J Heart Fail. 2021;23(2):277-285. doi:10.1002/ejhf.2027.
- Shah SJ, Fine N, Garcia-Pavia P, Klein AL, Fernandes F, Weissman NJ, et al. Effect of Tafamidis on Cardiac Function in Patients With Transthyretin Amyloid Cardiomyopathy: A Post Hoc Analysis of the ATTR-ACT Randomized Clinical Trial. JAMA Cardiol. 2024;9(1):25-34. doi:10.1001/jamacardio.2023.4147.
- Sperry BW, Sultan MB, Gundapaneni B, Tai SS, Witteles RM. Effect of Tafamidis on Renal Function in Patients With Transthyretin Amyloid Cardiomyopathy in ATTR-ACT. JACC CardioOncol. 2024;6(2):300-306. doi:10.1016/j.jaccao.2024.02.007.
- Witteles R, Jefferies JL, Kapa S, Cappelli F, Sultan MB, Gundapaneni B, et al. Atrial Fibrillation as a Prognostic Factor for All-Cause Mortality in Patients With Transthyretin Amyloid Cardiomyopathy. JACC CardioOncol. 2024;6(4):592-598. doi:10.1016/j.jaccao.2024.03.007.
- Miller AB, Januzzi JL, O'Neill BJ, Gundapaneni B, Patterson TA, Sultan MB, López-Sendón J. 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;148:146-150. doi:10.1016/j.amjcard.2021.02.035.
EM-GLB-RDT-0191 | July 2026 Page published: 14-Jul-2026
