Efficacy of Tafamidis in Patients with Hereditary or Wild-Type Transthyretin Amyloid Cardiomyopathy: Further Results from the ATTR-ACT Trial

Abstract

Purpose Transthyretin amyloid cardiomyopathy (ATTR-CM), an underdiagnosed, fatal disease caused by the deposition of transthyretin amyloid fibrils in the heart leading to heart failure, can be hereditary, due to mutations in the transthyretin gene, or wild-type. Tafamidis, a selective transthyretin stabilizer which prevents tetramer dissociation and amyloidogenesis, was recently shown to be an effective treatment for ATTR-CM patients in the international, multicenter, double-blind, placebo-controlled, randomized, Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT). Methods Pre-specified and post-hoc analyses of data from ATTR-ACT compared all-cause mortality, and the key secondary outcomes of change from baseline to Month 30 in six-minute walk test (6MWT) distance and Kansas City Cardiomyopathy Questionnaire overall score (KCCQ-OS), with tafamidis meglumine (80 mg or 20 mg) and placebo across hereditary and wild-type ATTR-CM patients. Results 106 hereditary (63 tafamidis, 43 placebo) and 335 wild-type patients (201 tafamidis, 134 placebo) were enrolled. The reduction in all-cause mortality with tafamidis compared with placebo was similar in hereditary (31.0%) and wild-type (29.4%) patients. This reduction was more pronounced in NYHA Class I and II patients (41.6% hereditary; 43.4% wild-type) than in NYHA Class III patients (20.5% hereditary; 11.6% wild-type). There was a significant and similar reduction in the decline in 6MWT distance in hereditary (mean [SE] difference from placebo, 79.61 [29.83] m; P=0.008) and wild-type (77.14 [10.78] m; P Conclusion ATTR-ACT, the largest randomized controlled trial in ATTR-CM, demonstrated that tafamidis significantly and clinically meaningfully improved survival, function and quality of life in patients with ATTR-CM. These analyses further support the efficacy of tafamidis in both wild-type and hereditary patients, and highlight the importance of early diagnosis and treatment. Together, these results provide strong evidence that tafamidis is an effective therapy for all patients with ATTR-CM.