Tafamidis in women with wild-type transthyretin cardiac amyloidosis: an international cohort study

AIMS: The natural history and response to tafamidis treatment in women with wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) remain insufficiently characterised. Current study aimed to explore sex-differences in clinical presentation, natural course and tafamidis treatment efficacy, focusing on women with ATTRwt-CM. METHODS AND RESULTS: An international, multicentric cohort of ATTRwt-CM subjects was evaluated, including for all-cause mortality. In total 1454 patients were studied (mean age 81±7y), including 307 (21.1%) females. At presentation, females were ∼3 years older than males with slightly worse phenotype, including higher indexed left ventricular wall thickness and National Amyloidosis Centre (NAC) disease stage (p<0.050). Heart failure with preserved ejection fraction and hypertension coincided more often in women (p=0.001). Natural disease course was poor without sex-difference, even when age-corrected (p=0.210). Tafamidis was initiated in 1055 patients, 12% less in females (p<0.001), although reasons for non-initiation and discontinuation did not show heterogeneity by sex (p=0.116 and p=0.304, respectively), indicating structural undertreatment. After 1.9 (0.9-3.3) years of median follow-up, 409 (28.1%) patients died. Tafamidis related to lower mortality in the overall and propensity score-matched cohort (n=742, HR 0.44, 95%CI 0.32-0.61, p<0.001), without sex-difference (female HR 0.76, 95%CI 0.52-1.11, p=0.150) nor sex-based treatment efficacy interaction (p=0.381). NAC disease stages strongly related to mortality under tafamidis treatment (HR 2.13%, 95%, 1.81-2.50, p<0.001), but female sex did not (HR 0.82, 95%CI 0.53-1.27, p=0.365). CONCLUSIONS: Women with ATTRwt-CM are prone to underdiagnosis and undertreatment, despite similar poor natural course and tafamidis treatment efficacy. Initiatives to increase diagnostic awareness and disease modifying treatment initiation in women are urgently needed.

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Journal
European Heart Journal - Quality of Care and Clinical Outcomes
Published
2026-04-22
DOI
https://doi.org/10.1093/ehjqcco/qcag074
Primary Topic
Amyloidosis: Diagnosis, Treatment, Outcomes
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article
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article

Tafamidis in women with wild-type transthyretin cardiac amyloidosis: an international cohort study

Sander Trenson, Emma Christiaen, Philippe Debonnaire, Nils de Marneffe et al.
European Heart Journal - Quality of Care and Clinical Outcomes
Amyloidosis: Diagnosis, Treatment, Outcomes
article

Tafamidis in women with wild-type transthyretin cardiac amyloidosis: an international cohort study

Sander Trenson, Emma Christiaen, Philippe Debonnaire, Nils de Marneffe, Alexandre Bohyn, Kris Bogaerts, Anne–Catherine Pouleur, René Tavernier, Mélanie Bézard, Steven Droogmans, Johan De Sutter, Ian Buysschaert, Robert Adam, Robbe Knapen, Philippe Timmermans, Ruxandra Jurcuţ, Nicolas Verheyen, Nora Schwegel, Matthias Dupont, Victor Sarli Issa, L Buytaert, Karl Dujardin, Nicolas Wyseure, N Ajmone Marsan, W L'hoyes, R Dulgheru, E Donal, M V Regeer, David Zach, Antoine Bondue
article en

Abstract

AIMS: The natural history and response to tafamidis treatment in women with wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) remain insufficiently characterised. Current study aimed to explore sex-differences in clinical presentation, natural course and tafamidis treatment efficacy, focusing on women with ATTRwt-CM. METHODS AND RESULTS: An international, multicentric cohort of ATTRwt-CM subjects was evaluated, including for all-cause mortality. In total 1454 patients were studied (mean age 81±7y), including 307 (21.1%) females. At presentation, females were ∼3 years older than males with slightly worse phenotype, including higher indexed left ventricular wall thickness and National Amyloidosis Centre (NAC) disease stage (p<0.050). Heart failure with preserved ejection fraction and hypertension coincided more often in women (p=0.001). Natural disease course was poor without sex-difference, even when age-corrected (p=0.210). Tafamidis was initiated in 1055 patients, 12% less in females (p<0.001), although reasons for non-initiation and discontinuation did not show heterogeneity by sex (p=0.116 and p=0.304, respectively), indicating structural undertreatment. After 1.9 (0.9-3.3) years of median follow-up, 409 (28.1%) patients died. Tafamidis related to lower mortality in the overall and propensity score-matched cohort (n=742, HR 0.44, 95%CI 0.32-0.61, p<0.001), without sex-difference (female HR 0.76, 95%CI 0.52-1.11, p=0.150) nor sex-based treatment efficacy interaction (p=0.381). NAC disease stages strongly related to mortality under tafamidis treatment (HR 2.13%, 95%, 1.81-2.50, p<0.001), but female sex did not (HR 0.82, 95%CI 0.53-1.27, p=0.365). CONCLUSIONS: Women with ATTRwt-CM are prone to underdiagnosis and undertreatment, despite similar poor natural course and tafamidis treatment efficacy. Initiatives to increase diagnostic awareness and disease modifying treatment initiation in women are urgently needed.

European Heart Journal - Quality of Care and Clinical Outcomes
Cliniques Universitaires Saint-Luc (BE), Université Libre de Bruxelles (BE), University of Liège (BE), Carol Davila University of Medicine and Pharmacy (RO), Medical University of Graz (AT), Leiden University Medical Center (NL), Universitair Ziekenhuis Leuven (BE), Statistics Belgium (BE), Jessa Hospital (BE), AZ Sint-Jan (BE), Universitair Ziekenhuis Brussel (BE), Centre Hospitalier Universitaire de Liège (BE), AZ Maria Middelares (BE), AZ Delta (BE), Ziekenhuis Oost-Limburg (BE), Centre Hospitalier Universitaire de Rennes (FR), Hasselt University (BE)
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Openalex Percentile: Top 10%
Amyloidosis: Diagnosis, Treatment, Outcomes
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