Early tafamidis treatment helps improve survival in patients with transthyretin amyloid cardiomyopathy

Perry Elliott, University College London, London, UK, and colleagues observed reduced mortality from all causes with continuous tafamidis treatment versus delayed tafamidis treatment (placebo then tafamidis) over a median follow-up of 5 years among patients with NYHA (New York Heart Association) class III symptoms at baseline.

The researchers reported, "Individuals with NYHA class III symptoms who received continuous tafamidis treatment in both the ATTR-ACT and long-term extension studies showed a 36% reduced hazard of all-cause mortality versus those receiving tafamidis only in the long-term extension analysis."

The cause for transthyretin amyloid cardiomyopathy is the myocardial deposition of variant or wild-type transthyretin amyloid. It is a progressive condition that results in heart failure. Early diagnosis and treatment can improve the outcomes, but, the median untreated survival is reported to be between 2 and 6 years.

There has been a debate on the value of disease-modifying treatment (such as tafamidis) in patients with ATTR-CM and severe heart failure symptoms. To put a rest to the ongoing debate, Dr Elliott and the team evaluated long-term all-cause survival in patients with NYHA class III symptoms in the ATTR-ACT long-term extension (LTE) study.

At baseline of ATTR-ACT, 31.3% of patients receiving tafamidis 80 mg and 35.6% receiving placebo had NYHA class III symptoms. Following 30 months of treatment, patients could join an ongoing LTE study to receive open-label tafamidis.

The authors reported the following findings:

• In an interim analysis of the LTE study (August 2021), all-cause mortality was lower among patients with NYHA class III symptoms who received continuous tafamidis in ATTR-ACT and the LTE study (hazard ratio: 0.64; median follow-up: 60 months), as compared with those who received placebo in ATTR-ACT and tafamidis in the LTE study (median follow-up: 56 months).
• Similar findings were observed in patients with NYHA class I/II symptoms at baseline ( tafamidis 80 mg n = 121; placebo n = 114; median follow-up of 61 and 60 months, respectively).

"In this study, though not designed or powered to precisely assess time to separation, treatment differences in mortality rate started to emerge during ATTR-ACT in both NYHA class I/II and III patients," the researchers wrote.

In the most recent interim analysis of the LTE study, the researchers observed a lower risk of all-cause mortality across NYHA classes I/II in patients with ATTR-CM receiving continuous tafamidis (80 mg/61 mg) from the start of ATTR-ACT versus those receiving placebo in ATTR-ACT and then tafamidis in the LTE study.

"These findings support tafamidis use in patients with early and advanced ATTR-CM and further emphasize the importance of prompt diagnosis and treatment initiation," they concluded.

Reference:

Elliott, P., Gundapaneni, B., Sultan, M. B., Ines, M., & Garcia-Pavia, P. Improved long-term survival with tafamidis treatment in patients with transthyretin amyloid cardiomyopathy and severe heart failure symptoms. European Journal of Heart Failure. https://doi.org/10.1002/ejhf.2974