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

• Published in: European heart journal Vol. 46; no. 11; pp. 1057 - 1070
• Main Authors: Debonnaire, Philippe, Dujardin, Karl, Verheyen, Nicolas, Pouleur, Anne-Catherine, Droogmans, Steven, Claeys, Mathias, Bohyn, Alexandre, Bogaerts, Kris, El Haddad, Milad, Christiaen, Emma, Wyseure, Nicolas, Zach, David K, Buytaert, Lars, Jacobs, Annemie, Buysschaert, Ian, Trenson, Sander, Van Hoeyweghen, Raf, Tavernier, René
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 13.03.2025
• Subjects: Aged, 80 and over; Amyloid Neuropathies, Familial - drug therapy; Amyloid Neuropathies, Familial - mortality; Benzoxazoles - therapeutic use; Cardiomyopathies - drug therapy; Cardiomyopathies - mortality; Clinical Research; Cohort Studies; Female; Humans; Male; Treatment Outcome; Octogenarian; Tafamidis; Cardiac amyloidosis; Cardiomyopathy; Mortality; Transthyretin
• ISSN: 0195-668X; 1522-9645; 1522-9645
• DOI: 10.1093/eurheartj/ehae923

In real-world, wild-type transthyretin cardiomyopathy is increasingly diagnosed in patients ≥ 80 years old (octogenarians), although being underrepresented in randomized clinical trials. Specific data on natural course and outcome under tafamidis treatment in octogenarians are therefore scarce. The impact of tafamidis treatment on mortality in real-world wild-type transthyretin cardiomyopathy octogenarians was studied. An international, multicentre cohort study of 710 consecutive wild-type transthyretin cardiomyopathy patients with mean follow-up of 2.2 ± 1.8 years for all-cause mortality endpoint was performed. The cohort consisted of 58.5% (415/710) octogenarians (85 ± 4 years, 74.2% male). Before tafamidis availability, natural course in octogenarians (148/257) vs. non-octogenarians (109/257) was poor, with 16% 1-year and 71% 5-year mortality vs. 8% and 47%, respectively (P < .001). Since tafamidis availability, 70.1% (253/361) octogenarians were initiated on tafamidis vs. 83.7% (231/276) non-octogenarians (P < .001). Tafamidis discontinuation was similar (octogenarians 10.3% and non-octogenarians 7.4%; P = .260). Overall tafamidis treated vs. untreated octogenarians had better unadjusted survival (P < .001), with 5% 1-year and 24% 3-year mortality. Tafamidis treatment associated with lower mortality after propensity score matching on baseline variables, including age, National Amyloidosis Centre stage, and New York Heart Association class in on average 394 subjects [hazard ratio (HR) = 0.53, 95% confidence interval (CI) 0.34-0.84, P = .007], also in octogenarians (HR = 0.57, 95% CI 0.33-1.01, P = .053). Neither age at diagnosis (P = .217) nor at treatment initiation (P = .154) interacted with tafamidis mortality benefit. Octogenarians had poorer survival despite tafamidis, when initiated at ≥90 years (HR = 3.3, 95% CI 1.10-9.53, P = .033) and National Amyloidosis Centre Stage ≥3 (HR = 2.4, 95% CI 0.87-6.46, P = .090). Real-world tafamidis treatment improves survival without age affecting treatment efficacy, although mortality remains considerable in octogenarians.