Tafamidis in women with wild-type transthyretin cardiac amyloidosis: an international cohort study.
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.
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).
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.
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).
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.
Authors
Debonnaire Debonnaire, L'Hoyes L'Hoyes, Dujardin Dujardin, Donal Donal, Verheyen Verheyen, Dupont Dupont, De Sutter De Sutter, Timmermans Timmermans, Pouleur Pouleur, Droogmans Droogmans, Issa Issa, Dulgheru Dulgheru, Regeer Regeer, Jurcut Jurcut, Bondue Bondue, Bohyn Bohyn, Bogaerts Bogaerts, Christiaen Christiaen, Wyseure Wyseure, Bezard Bezard, Zach Zach, Schwegel Schwegel, Knapen Knapen, Buytaert Buytaert, de Marneffe de Marneffe, Ajmone Marsan Ajmone Marsan, Adam Adam, Tavernier Tavernier, Buysschaert Buysschaert, Trenson Trenson
View on Pubmed