Long-term efficacy of tafamidis in patients with transthyretin amyloid cardiomyopathy by National Amyloidosis Centre stage.

Objective: Tafamidis is an approved treatment for patients with transthyretin amyloid cardiomyopathy (ATTR-CM) based on the 30-month Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT). This post-hoc analysis evaluated outcomes in ATTR-ACT and its long-term extension study (LTE) by baseline National Amyloidosis Centre (NAC) stage. Results: Patients received either the approved dose of tafamidis 80 mg or placebo in ATTR-ACT and tafamidis in the LTE. All-cause and cardiovascular (CV)-related mortality, CV-related hospitalizations, and Kansas City Cardiomyopathy Questionnaire overall summary and clinical summary (KCCQ-OS/CS) scores were assessed up to 90 months of follow-up. Of 353 patients, 350 were evaluable for NAC staging. At baseline, 42%, 38%, and 20% were NAC stage I, II, and III, respectively. At the end of study, all-cause mortality was lower in the continuous tafamidis versus placebo to tafamidis groups at NAC stages I (36% vs. 61%; hazard ratio [HR] 0.43, p < 0.001) and II (55% vs. 74%; HR 0.51, p = 0.003); with a numerical trend at stage III (69% vs. 88%; HR 0.75, p = 0.298). Survival curves diverged early in patients at NAC stage I, but later at higher stages. Similar patterns were observed for CV-related mortality. Continuous tafamidis versus placebo to tafamidis groups at NAC stages I/II had lower CV-related hospitalization rates and frequently smaller declines in KCCQ-OS/CS scores over follow-up; with favourable trends at stage III. Conclusions: Tafamidis treatment reduced the risk of mortality and hospitalization in patients with NAC stages I/II ATTR-CM, with favourable trends at stage III. This illustrates the importance of early diagnosis and initiation of disease-modifying therapy.

Background: ClinicalTrials.gov, NCT01994889, NCT02791230.