Maurer MS, et al. - Researchers designed the Transthyretin Amyloidosis Cardiomyopathy Clinical Trial (ATTR-ACT) to assess the efficacy and safety of tafamidis in patients with hereditary and wild-type transthyretin amyloid cardiomyopathy. Findings suggest reductions in all-cause mortality and cardiovascular-related hospitalizations, as well as a reduction in functional capacity decline and quality of life was seen with with tafamidis vs with placebo among these patients.

Methods

• Researchers conducted a multicenter, international, double-blind, placebo-controlled, phase 3 trial including 441 patients with transthyretin amyloid cardiomyopathy.
• The patients were randomly assigned in a 2:1:2 ratio to receive 80 mg of tafamidis, 20 mg of tafamidis, or placebo for 30 months.
• They hierarchically determined all-cause mortality, followed by frequency of cardiovascular-related hospitalizations according to the Finkelstein–Schoenfeld method in the primary analysis.
• The change from baseline to month 30 for the 6-minute walk test and the score on the Kansas City Cardiomyopathy Questionnaire–Overall Summary (KCCQ-OS), in which higher scores indicate better health status, were the key secondary end points.

Results

• In the primary analysis, the 264 patients who received tafamidis showed lower all-cause mortality and rates of cardiovascular-related hospitalizations than the 177 patients who received placebo (P < 0.001).
• Tafamidis resulted in reduced all-cause mortality than placebo (78 of 264 [29.5%] vs 76 of 177 [42.9%]; hazard ratio, 0.70; 95% confidence interval [CI], 0.51 to 0.96) and a reduced rate of cardiovascular-related hospitalizations, with a relative risk ratio of 0.68 (0.48 per year vs 0.70 per year; 95% CI, 0.56 to 0.81).
• Tafamidis was also noted to be correlated with a lower rate of decline in distance for the 6-minute walk test (P < 0.001) and a lower rate of decline in KCCQ-OS score at month 30 (P < 0.001).
• The groups were similar in terms of the incidence and types of adverse events.