Tafamidis in Transthyretin Amyloid Cardiomyopathy

Abstract

Background— Transthyretin (TTR) amyloidosis is a progressive systemic disorder caused by misfolded TTR monomers that cumulatively deposit in the heart and systemically as amyloid. Methods and Results— This phase 2 open-label trial evaluated the stabilization of TTR tetramers using 20 mg of tafamidis daily at week 6 (primary end point), month 6, and month 12, as well as safety of tafamidis treatment and efficacy with respect to progression of TTR amyloid cardiomyopathy. Thirty-one wild-type patients (median age, 76.7 years; 93.5% men) with a median disease duration of 55.6 months and mild to moderate heart failure (96.8%; New York Heart Association, classes I–II) were enrolled. Thirty of 31 patients (96.8%) achieved TTR stabilization after 6 weeks and 25 of 28 patients (89.3%) after 12 months. After 12 months of treatment, 3 patients discontinued prematurely, 2 patients died, 7 patients were hospitalized because of cardiovascular events, 20 of 28 patients demonstrated preserved New York Heart Association classification status, but 15 of 31 (48.4%) patients had clinical progression (eg, admission for cardiac failure, atrial fibrillation, and syncope). N-terminal prohormone brain natriuretic peptide levels did not increase significantly over time, troponin I and troponin T increased moderately, and no consistent clinically relevant changes were seen in echocardiographic cardiac assessments. Tafamidis treatment was generally well tolerated although 7 of 31 patients had bouts of diarrhea. Conclusions— Tafamidis treatment effectively achieved and maintained TTR stabilization and was well tolerated. The absence of significant changes in most biochemical and echocardiographic parameters suggests that further evaluation of tafamidis in TTR amyloid cardiomyopathy is warranted. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00694161.

Diagnostic utility of cardiac troponin T level in patients with cardiac amyloidosis

“…Treatment and prognosis of cardiac amyloidosis vary greatly depending on the amyloid fibril precursor. Therefore, early detection and classification are important for the selection of appropriate therapeutic strategies such as chemotherapy, liver transplantation, and novel transthyretin‐modifying therapeutics 1, 2, 3, 4…”

Clinical Masks of Amyloidosis With the Heart Involvement: Modern Diagnostic Issues

“…Если в терапию AL-ами-лоидоза внедрены активные схемы на основе мелфа-лана, бортезомиба, то для TTR-амилоидоза до послед-него времени таких препаратов не было. В начале 2017г в России будет зарегистрирован препарат тафа-мидис, который относят к классу стабилизаторов TTR; показанием к его назначению пока считают амилоид-ную нейропатию, в отношении сердца эффект можно оценить как частичную стабилизацию [30,31], однако повышение дозы (с 20 до 60-80 мг/сут.) может приве-сти к усилению эффекта [32].…”

Non-Val30met-Transthyretin Amyloid Cardiomyopathy. Literature Review and Clinical Case

“…Французский мар-кетинговый комитет в сентябре 2011г дал разрешение на применение тафамидиса (Vyndaqel, Pfizer, Нью-Йорк, США) для лечения TTR-амилоидоза у взрос-лых пациентов с симптоматической полинейропа-тией стадии I [15][16][17].…”

“…Эффективность препарата пока-зана у больных с Val30Met ТТР-полинейропатией. Тафамидис хорошо переносится у пациентов на 1 стадии, хотя могут быть побочные эффекты (желу-дочно-кишечные расстройства, мочеполовые инфек-ции) [16,17].…”