Tafamidis in women with wild-type transthyretin cardiac amyloidosis: an international cohort study
P Debonnaire, K Dujardin, E Donal, N Verheyen, M Dupont, J De Sutter, P J R Timmermans, A C Pouleur, S Droogmans, V Sarli Issa, R Dulgheru, M Regeer, R Jurcut, A Bondue, S TrensonAbstract
Background
Female natural and tafamidis treated course in wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) remains largely elusive.
Purpose
Current study aimed to explore sex-differences in clinical presentation, natural course and tafamidis treatment efficacy, focusing on women with ATTRwt-CM.
Methods
An international, multicentric cohort of ATTRwt-CM subjects was evaluated, including for all-cause mortality.
Results
In total 1454 patients were studied (mean age 81±7 years), 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 rate were equal between sexes (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.Graphical abstractFor image description, please refer to the figure legend and surrounding text.Mortality overall and PSM populationFor image description, please refer to the figure legend and surrounding text.