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

Abstract

Aims The natural history and response to tafamidis treatment in women with wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) remain insufficiently characterized. 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 similar to 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). Conclusion 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.