Survival analysis of tafamidis use in patients with ATTR cardiac amyloidosis

Abstract

Abstract Introduction Transthyretin cardiac amyloidosis (ATTR-CM) is a condition in which amyloid fibrils are deposited within the myocardium causing a restrictive cardiomyopathy & resulting heart failure condition. With increasing recognition, a challenge posed, surrounds decisions on optimal treatment strategies. For patients with predominant cardiac amyloidosis, without peripheral/autonomic nervous system involvement, targeted treatments are limited, although the medication tafamidis – a TTR stabiliser, is available since approval by the FDA in 2019 & the European commission in 2020. Aim This study aims to analyse the real-world benefit of tafamidis use in patients with ATTR-CM attending the National Amyloidosis Centre (NAC), UK with regards overall survival from diagnosis when compared to those not on targeted treatment. Methods This was a retrospective study using data taken from a database at the NAC, as all patients included attend the NAC, UK. Patients on tafamidis were matched to control patients (not on targeted treatment) for age, ATTR NAC stage at diagnosis and type of ATTR (i.e. variant or wild-type). Outcome and survival analysis were determined using cox regression analysis and Kaplan-Meier curve using SPSS (V9.0). Results The demographics of patients in both groups are detailed in figure 1. There were 75 patients in both the treatment & control groups. The median follow-up time from diagnosis to data acquisition in the control group was 3.7 years [IQR1.8-5.8] compared to 4.3 years [IQR 3.6-5.4] in the treatment group (p = 0.03). Of note the median duration from diagnosis to starting tafamidis was 2.1 years [1.2-3.2]. Using cox regression analysis, tafamidis use was predictive of a reduced likelihood of death (R = -1.4, p<0.001) [OR 0.24 95%CI 0.12-0.47]. Increasing NAC stage at diagnosis (R = 0.42, P = 0.03), [OR1.5, 95%CI 1.04-2.22] was predictive of increased likelihood of death. Increasing age (R = 0.03, p = 0.07) [OR 1.03, 95%CI 0.98-1.07] was non-significantly associated with increased likelihood of death. There was similarly a significant increase in mortality within the control/non-treatment group of patients (P<0.001) which was reflected in the Kaplan-Meier survival curve (p<0.001). Conclusions In this retrospective analysis, tafamidis use in 75 patients with ATTR-CM, initiated after a median of 2.2 year [IQR1.2-3.2] following diagnosis, was associated with significantly reduced mortality when compared to an untreated matched control group. Survival from diagnosis was similarly improved in the tafamidis group as depicted by the Kaplan-Meier curve. This real-world data suggests support for the use of tafamidis in treating those with ATTR-CM.