Systematic Review of Prognostic Factors and Treatment Effect Modifiers for Transthyretin Amyloid Cardiomyopathy
Author(s)
Chris G. Cameron, BSc, MSc, PhD1, Jaydeep Das, BSc, MSc2, Sidsel Høier Gamborg Møller, MD, PhD3, Mary Chappell, BSc, MSc, PhD4, Erin Barker, BSc, MSc5.
1EVERSANA, Sydney, NS, Canada, 2Novo Nordisk A/S, Bangalore, India, 3Novo Nordisk A/S, Bagsvaerd, Denmark, 4York Health Economic Consortium, York, United Kingdom, 5York Health Economics Consortium, York, United Kingdom.
1EVERSANA, Sydney, NS, Canada, 2Novo Nordisk A/S, Bangalore, India, 3Novo Nordisk A/S, Bagsvaerd, Denmark, 4York Health Economic Consortium, York, United Kingdom, 5York Health Economics Consortium, York, United Kingdom.
OBJECTIVES: To identify prognostic factors and treatment effect modifiers relevant to health outcomes, such as mortality, in patients with transthyretin amyloid cardiomyopathy (ATTR-CM).
METHODS: A systematic review of studies in patients with ATTR-CM was conducted to identify factors predictive of outcomes, either independently (prognostic) or in response to treatment (effect modifiers). Longitudinal studies (excluding case reports) were eligible where reporting adjusted analyses of the impact of factors on long-term outcomes. Six journal databases, two trial registries and four HTA websites were searched. Studies reporting multivariate models adjusting for at least age, a measure of cardiovascular health and a measure of kidney function were included.
RESULTS: 28 observational studies, including 12,364 participants, were included. Since all reported the impact of factors in the presence of treatment, it was unclear whether factors were prognostic, effect modifiers or both. Pooled estimates for five factors demonstrated statistically significant associations with all-cause mortality: age (hazard ratio (HR) per year increase 1.06; 95% CI 1.04 to 1.08), LVEF (HR per % increase 0.98; 95% CI 0.95 to 0.99), ATTR genotype (variant-type vs wild-type, HR 1.64; 95% CI 1.33 to 2.00), NAC stage (stage II vs I, HR 1.81; 95% CI 1.09 to 3.03 and stage III vs I, HR 4.42; 95% CI 1.46 to 13.36) and NYHA class (class III/IV vs class I/II, HR 1.85; 95% CI 1.14 to 2.99). Decreased eGFR, increased NT-proBNP and male sex were associated with all-cause mortality, but findings were not statistically significant. Troponin-T and Columbia stage demonstrated statistically significant associations with mortality across studies without meta-analysis.
CONCLUSIONS: This review identified key predictive factors for all-cause mortality in ATTR-CM: age, LVEF, ATTR type, NAC stage, and NYHA class. Potentially predictive factors, including eGFR, NT-proBNP, and sex, require further validation. These findings inform risk stratification, clinical decision-making, and future comparative effectiveness research.
METHODS: A systematic review of studies in patients with ATTR-CM was conducted to identify factors predictive of outcomes, either independently (prognostic) or in response to treatment (effect modifiers). Longitudinal studies (excluding case reports) were eligible where reporting adjusted analyses of the impact of factors on long-term outcomes. Six journal databases, two trial registries and four HTA websites were searched. Studies reporting multivariate models adjusting for at least age, a measure of cardiovascular health and a measure of kidney function were included.
RESULTS: 28 observational studies, including 12,364 participants, were included. Since all reported the impact of factors in the presence of treatment, it was unclear whether factors were prognostic, effect modifiers or both. Pooled estimates for five factors demonstrated statistically significant associations with all-cause mortality: age (hazard ratio (HR) per year increase 1.06; 95% CI 1.04 to 1.08), LVEF (HR per % increase 0.98; 95% CI 0.95 to 0.99), ATTR genotype (variant-type vs wild-type, HR 1.64; 95% CI 1.33 to 2.00), NAC stage (stage II vs I, HR 1.81; 95% CI 1.09 to 3.03 and stage III vs I, HR 4.42; 95% CI 1.46 to 13.36) and NYHA class (class III/IV vs class I/II, HR 1.85; 95% CI 1.14 to 2.99). Decreased eGFR, increased NT-proBNP and male sex were associated with all-cause mortality, but findings were not statistically significant. Troponin-T and Columbia stage demonstrated statistically significant associations with mortality across studies without meta-analysis.
CONCLUSIONS: This review identified key predictive factors for all-cause mortality in ATTR-CM: age, LVEF, ATTR type, NAC stage, and NYHA class. Potentially predictive factors, including eGFR, NT-proBNP, and sex, require further validation. These findings inform risk stratification, clinical decision-making, and future comparative effectiveness research.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
CO230
Topic
Clinical Outcomes, Epidemiology & Public Health
Topic Subcategory
Relating Intermediate to Long-term Outcomes
Disease
Cardiovascular Disorders (including MI, Stroke, Circulatory), No Additional Disease & Conditions/Specialized Treatment Areas