The Bottom Line: . In a study of diflunisal in ATTR cardiac amyloidosis (both mutant and wt), stable mean left ventricular (LV) mass, LVEF and cardiac biomarkers were seen during the course of therapy. Nephrotoxicity and volume overload was observed as AEs. A RCT of diflunisal for familial amyloid polyneuropathy (FAP; caused by mutant ATTR) reported neurological stability at 2 years in 29.7 % of patients in the diflunisal arm versus 9.4 % of the placebo arm. Tafamidis, a kinetic stabilizer of TTR protein, is active in FAP and leads to a delay in peripheral neurologic impairment, with minimal AEs. A phase 2 study of tafamidis in ATTR amyloid cardiomyopathy showed TTR stabilization in
97 % of wt patients with mild to moderate CHF.
Summary: OLT remains the benchmark for treatment of ATTR amyloidosis; however, progression of cardiac amyloidosis after OLT due to an increase in the wild:mutant TTR ratio is concerning. Development of BTTR stabilizers is a promising arena in hereditary amyloidosis and further studies are needed to ascertain survival benefit in those with cardiac involvement.