Tafamidis in ATTR-CM: Study Reports 39 Percent Mortality, Calls for Better Treatment Strategies

New real-world data suggest that two out of every five patients with transthyretin amyloid cardiomyopathy treated with tafamidis (Vyndamax and Vyndaqel; Pfizer) may not survive beyond four years. However, despite the high mortality rate, researchers emphasize that these findings should be viewed positively, considering that tafamidis was the first approved treatment for ATTR-CM and has significantly advanced disease management in recent years.

The ATTR-ACT trial established that tafamidis improves survival and reduces cardiovascular hospitalizations in transthyretin amyloid cardiomyopathy, a progressive and life-threatening condition caused by the deposition of misfolded transthyretin proteins in the heart. This leads to restrictive cardiomyopathy and heart failure. As disease recognition and early diagnosis improve, the epidemiology of ATTR-CM is rapidly evolving. Tafamidis, the only approved disease-modifying therapy, stabilizes transthyretin to slow disease progression and enhance survival. However, real-world long-term data on its effectiveness remain limited, highlighting the need for further research on tafamidis outcomes in clinical practice.

Against the above background, Ahmad Masri, Amyloidosis Center, Knight Cardiovascular Institute, Oregon Health & Science University, Portland, Oregon, USA, and colleagues aimed to assess the long-term clinical outcomes of patients with ATTR-CM receiving tafamidis treatment in a contemporary setting.

For this purpose, the researchers enrolled patients with ATTR-CM who had received at least one dose of tafamidis between 2018 and 2021 at five amyloidosis centers in the United States, assessing all-cause mortality as the primary outcome.

The following were the key findings of the study:

• The study included 624 patients with a mean age of 76.9 ± 8.4 years, of whom 12.5% were female and 17.5% were Black.
• Among the participants, 17.5% had variant ATTR-CM.
• At the time of tafamidis initiation:
  • 52% had New York Heart Association (NYHA) functional class II.
  • 34% had NYHA functional class III.
  • 40% were classified as National Amyloidosis Center (NAC) Stage ≥II.
  • 38% were in Columbia Stage ≥II.
  • The median NT-proBNP level was 1,914 (957-3,914) pg/mL.
• Over a median follow-up of 43.2 months, 38.6% of patients died.
• The probability of survival at 65 months was 54.1%.
• In a subgroup of patients who received tafamidis within six months of their ATTR-CM diagnosis (n = 397, 63.6%), the survival probability at 65 months was 49.6%.

The researchers revealed that in a contemporary cohort of ATTR-CM patients treated with tafamidis, 39% of patients died over a median follow-up of 43 months, with a 54% survival probability at 65 months. They note that continuous evaluation of the evolving disease trajectory and patient outcomes remains crucial for advancing research in this field.

"Further efforts are needed to deepen the understanding of the ATTR-CM burden, its progression, and strategies to enhance patient outcomes beyond existing therapies," the researchers concluded.

Reference:

Masri A, Bhattacharya P, Medoff B, et al. A multicenter study of contemporary long-term tafamidis outcomes in transthyretin amyloid cardiomyopathy. JACC CardioOncol. 2025;Epub ahead of print.