Natural history and progression of transthyretin amyloid cardiomyopathy: insights from ATTR‐ACT

Abstract

Aims Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive, fatal disorder that remains underdiagnosed. The Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT) was the first large clinical trial to include both wild-type (ATTRwt) and hereditary (ATTRv) patients. A description of the natural history of ATTR-CM, utilizing data from placebo-treated patients in ATTR-ACT, will provide a greater understanding of presentation and progression of ATTR-CM and may aid in disease awareness, earlier diagnosis and treatment monitoring. Methods and results Changes in clinical endpoints (mortality, cardiovascular [CV]-related hospitalizations, 6-min walk test [6MWT] distance and Kansas City Cardiomyopathy Questionnaire Overall Summary [KCCQ-OS] score) from baseline to Month 30 in the 177 patients (134 ATTRwt, 43 ATTRv) who received placebo in ATTR-ACT were assessed. ATTRwt patients tended to have less severe disease at baseline. Over the duration of ATTR-ACT, there were 76 (42.9%) all-cause deaths, and 107 (60.5%) patients had a CV-related hospitalization. There was a lower proportion of all-cause deaths in ATTRwt (49, 36.6%) than ATTRv (27, 62.8%). There was a similar, steady decline in mean (SD) 6MWT distance from baseline to Month 30 in ATTRwt (93.9 [93.7] m) and ATTRv (89.1 [107.2] m) patients. The decline in mean (SD) KCCQ-OS score was less severe in ATTRwt (13.8 [20.7]) than ATTRv (21.0 [26.4]) patients. Conclusions Patients with ATTR-CM experience a severe, progressive disease. In ATTR-ACT, placebo-treated patients with ATTRv, compared with ATTRwt, had more severe disease at baseline, and their disease progressed more rapidly as shown by mortality, hospitalizations and quality of life over time.

Sex-related differences in the clinical characteristics of wild-type transthyretin amyloidosis cardiomyopathy

“…In fact, the cardiac amyloid load tended to be lower in the female patients in our study. In the ATTR-ACT trial, the LVEF decreased by 5% decreased over a 30-month follow-up period in patients with ATTRwt-CM [29] . This result suggests that progression of ATTR-CM decreases the LVEF.…”

Baseline Characteristics and Secondary Medication Adherence Patterns Among Patients Receiving Tafamidis Prescriptions: A Retrospective Analysis Using a National Specialty Pharmacy Dispensing Database

“…Without treatment, patients with ATTR-CM experience severe and progressive disease that correlates to frequent hospitalizations and poor survival. 6 Patients with an accumulation of variant (ATTRv) transthyretin amyloid fibrils also experience a more rapid disease progression and diminished quality of life. 6 Based on its mechanism of stabilization of transthyretin to prevent the formation and the accumulation of amyloid plaques, timely diagnosis and treatment, including with tafamidis, is paramount to limiting disease progression, cardiovascular-related hospitalizations, and mortality.…”

“… 6 Patients with an accumulation of variant (ATTRv) transthyretin amyloid fibrils also experience a more rapid disease progression and diminished quality of life. 6 Based on its mechanism of stabilization of transthyretin to prevent the formation and the accumulation of amyloid plaques, timely diagnosis and treatment, including with tafamidis, is paramount to limiting disease progression, cardiovascular-related hospitalizations, and mortality. 13–15 , 17–20 The current analysis demonstrates high rates of adherence among patients taking tafamidis in the real world (75% to 100% of the patients having adherence ≥80%), especially by real-world standards and within the cardiology setting.…”

“… 4 Ultimately, the disease proves fatal (median survival 2 to 6 years). 6 Prior to 2019, no proven pharmacotherapies were available for patients with ATTR-CM, and the only treatment was heart transplant. 4 , 7–10 The discovery and subsequent regulatory approval of tafamidis was transformative to the treatment paradigm.…”

Real-World Characteristics of Patients with Wild-Type Transthyretin Amyloid Cardiomyopathy: An Analysis of Electronic Healthcare Records in the United States

“…ATTR formation can also be idiopathic and associated with aging, which can cause a condition called wild-type ATTR-CM (ATTRwt-CM) [1,2]. Without appropriate management and treatment, survival for patients with ATTRwt-CM is reported to be approximately 3.6 years; however, this may be increased with earlier diagnosis and treatment [3][4][5][6][7][8][9]. Evidence suggests that ATTRwt-CM is an underdiagnosed cause of heart failure in older adults [7,8,[10][11][12].…”