Transthyretin (ATTR) cardiac amyloidosis is a progressive infiltrative cardiomyopathy caused by the extracellular deposition of misfolded transthyretin protein in the myocardium, occurring either as wild-type or hereditary (variant) forms. (1) The ATTR-ACT trial (Tafamidis in Transthyretin Cardiomyopathy Clinical Trial) demonstrated that tafamidis, a transthyretin stabilizer, significantly reduced all-cause mortality and cardiovascular-related hospitalizations while attenuating the decline in functional status and quality of life in patients with ATTR cardiomyopathy. (2) Based on these findings, tafamidis received regulatory approval in the United States and Europe in 2019 for the treatment of both wild-type and variant ATTR cardiomyopathy. Notably, tafamidis was well tolerated, with adverse event rates similar to those observed with placebo.

Tafamidis is also known to inhibit breast cancer resistance protein (BCRP), an efflux transporter involved in drug metabolism and disposition. Adenosine triphosphate cassette transporter subfamily G, member 2 (ABCG2) gene encodes BCRP. (3) Inhibition of BCRP can increase plasma concentrations of its substrates, including statins such as rosuvastatin, as noted in the prescribing information. Pharmacokinetic studies confirm that BCRP inhibition may enhance systemic exposure to statins – 2-fold for rosuvastatin. (4, 5, 6) Given that risk factors for statin-induced myopathy—such as advanced age, polypharmacy, and multisystem disease (7)—are prevalent in the ATTR-CM population, potential drug-drug interactions in this setting warrant careful consideration.