Abstract
Tafamidis was shown to significantly reduce mortality in the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT) and is approved for the treatment of patients with transthyretin amyloid cardiomyopathy (ATTR-CM). Patients who completed ATTR-ACT were eligible to enroll in an ongoing, long-term extension study (LTE) providing data on the long-term efficacy of tafamidis.
Five-year survival data from ATTR-ACT and the LTE will further characterize the improved survival in patients treated with tafamidis.
Patients with ATTR-CM (both variant [ATTRv] and wild-type [ATTRwt]) who completed ATTR-ACT (patients were randomized to tafamidis meglumine 80 mg, 20 mg, or placebo for 30 months) could enroll in the ongoing LTE and continue to be treated with the same dose of tafamidis or, if previously treated with placebo, be randomized to tafamidis meglumine 80 mg or 20 mg. All patients in the LTE transitioned to tafamidis free acid 61 mg (a new formulation bioequivalent to tafamidis meglumine 80 mg). All-cause mortality was assessed by Cox proportional hazards model (as of March 20, 2020). Patients treated with tafamidis meglumine 80 mg in ATTR-ACT and the LTE who transitioned to tafamidis free acid 61 mg (continuous tafamidis) were compared with patients treated with placebo in ATTR-ACT who transitioned to tafamidis in the LTE (placebo to tafamidis).
There were 176 continuous tafamidis (median follow-up 58.5 months) and 177 placebo to tafamidis (median follow-up 57.1 months) patients. The preliminary 5-year survival rate with continuous tafamidis was 53.2% vs 32.4% with placebo to tafamidis. There was a significant reduction of 41.2% in the risk of all-cause mortality with continuous tafamidis vs placebo to tafamidis (hazard ratio [HR], 0.5878; 95% CI, 0.4385-0.7880; P=0.0004). The preliminary 5-year survival rate was improved with continuous tafamidis vs placebo to tafamidis in both ATTRwt (57.8% vs 36.3%; HR, 0.6105; 95% CI, 0.4298-0.8671; P=0.0058) and ATTRv (39.1% vs 20.9%; HR, 0.5739; 95% CI, 0.3320-0.9922; P=0.0468) patients, and in baseline New York Heart Association (NYHA) class I/II (61.4% vs 40.3%; HR, 0.5562; 95% CI, 0.3765-0.8218; P=0.0032) and NYHA class III (35.0% vs 18.0%; HR, 0.6470; 95% CI, 0.4131-1.0132]; P=0.0571) patients.
Tafamidis significantly improved survival over 5 years in patients with ATTR-CM. Improvements in 5-year survival with tafamidis were also observed in patients regardless of genotype and NYHA class. That survival was comparatively poorer in patients with more severe disease, and in those initially treated with placebo in ATTR-ACT, highlights the importance of early diagnosis and treatment.