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Efficacy of Tafamidis in Transthyretin Amyloid Cardiomyopathy
Quick Takes
- A significantly higher proportion of transthyretin amyloid cardiomyopathy (ATTR-CM) patients had improvements in health status and functional status with tafamidis compared with placebo at every time point until 30 months of follow-up compared with baseline.
- The differences in health status and functional status in ATTR-CM patients receiving tafamidis compared with placebo increased with increasing follow-up duration.
Study Questions:
What proportion of patients with transthyretin amyloid cardiomyopathy (ATTR-CM) demonstrated improved functional and health status after 30 months of treatment with tafamidis or placebo?
Methods:
This was a post hoc analysis of ATTR-ACT (Tafamidis in Transthyretin Cardiomyopathy Clinical Trial), which randomized patients aged 18-90 years with ATTR-CM (hereditary or wild type) to either placebo or 20 mg or 80 mg tafamidis. Endpoints for this study included 6-minute walk test (6MWT), Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS) score, N-terminal pro–B-type natriuretic peptide (NT-proBNP) score, patient global assessment of health, and New York Heart Association (NYHA) class. NT-proBNP was assessed at baseline, months 12 and 30, and all other endpoints were assessed every 6 months. Overall follow-up duration was 30 months.
Results:
Overall, 441 patients were enrolled across 48 sites and 176 received tafamidis 80 mg, 88 received tafamidis 20 mg, and 177 received placebo. Median age was 75 years in tafamidis recipients and 74 years in the placebo cohort. The majority were male and White. Temporal trends comparing changes from baseline to every follow-up assessment made every 6 months showed a mean decline in both tafamidis- and placebo-treated patients for all endpoints. However, across all endpoints, a significantly higher proportion had improvements on tafamidis compared with placebo at every time point until 30 months of follow-up compared with baseline. These differences grew as the follow-up time increased. These proportions for tafamidis vs. placebo at 30 months for 6MWT were 19% vs. 5%, for KCCQ-OS were 26% vs. 10%, NT-proBNP were 24% vs. 6%, patient global assessment were 27% vs. 11%, and improvement in NYHA class were 9% vs. 5%. These translated to statistically significant odds ratio (OR) in favor of tafamidis compared with placebo by month 30: for 6MWT OR 4.9, KCCQ-overall summary OR 3.3, NT-proBNP OR 5.3, patient global assessment of health OR 2.9, and NYHA class improvement OR 2.0.
Conclusions:
In a post hoc analysis of a randomized trial comparing tafamidis with placebo in ATTR-CM, tafamidis was associated with a higher proportion of patients experiencing an improvement in functional and health status at every 6-month follow-up until 30 months of follow-up. The differences in health status and functional status between tafamidis and placebo recipients grew progressively with increasing follow-up duration.
Perspective:
ATTR-CM is associated with a dismal prognosis with an untreated median survival of 2-5 years following diagnosis. More recently, newer treatment options including tafamidis have emerged. Tafamidis stabilizes the TTR protein and prevents further deposition into the myocardium. This study shows that ATTR is a progressive disease and the overall trends over the entire duration of follow-up demonstrated a mean decline in measures of functional status and health status. However, these data also demonstrate that use of tafamidis correlated with a significantly larger proportion of patients experiencing improvements in their functional status and health status compared with placebo. More importantly, these differences grew over the duration of follow-up. While these are big improvements for a condition previously considered terminal, there is a substantial proportion of patients who experienced no improvement in health status or functional status with tafamidis.
Clinical Topics: Geriatric Cardiology, Heart Failure and Cardiomyopathies, Acute Heart Failure, Heart Failure and Cardiac Biomarkers
Keywords: Amyloidosis, Cardiomyopathies, Functional Status, Geriatrics, Health Status, Heart Failure, Myocardium, Natriuretic Peptide, Brain, Prealbumin, Treatment Outcome
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