Tafamidis in transthyretin amyloid cardiomyopathy

Transthyretin is primarily synthesized in the liver and transports thyroxine vitamin A body. The transthyretin when dissociated into monomers can misfold ultimately form amyloid fibrils. There are two types of ATTR amyloidosis: hereditary (caused by mutations TTR gene) wild-type (also referred to as senile systemic amyloidosis). Amyloid cardiomyopathy develop patients with both amyloidosis, has a later onset characterized progressive heart failure leading death within few years after diagnosis. Tafamidis an oral-administered small molecule that binds inhibits tetramer dissociation, rate-limiting step amyloidosis. Long-term efficacy safety tafamidis were shown familial polyneuropathy. objective phase 3 international, multicenter, double-blind, placebo-controlled, randomized ATTR-ACT study was evaluate efficacy, safety, tolerability (20 or 80 mg orally QD) comparison placebo 441 nonhereditary (median age 75 years, 90% males). At month 30, treatment associated lower risk all-cause mortality (by 30%) rate cardiovascular related hospitalizations 32%) than resulted decline distance for 6-minute walk test KCCQ-OS score. data from extension supports optimal dose (bioequivalent free acid 61 mg).