Natural history and impact of treatment with tafamidis on major cardiovascular outcome-free survival time in a cohort of patients with transthyretin amyloidosis

Abstract

Hereditary (ATTRv) and senile (ATTRwt) transthyretin amyloidosis are severe and fatal systemic diseases, characterised by amyloid fibrillar accumulation principally in the heart or peripheral nerves (or both). Since 2012, tafamidis is used in France to treat patients with ATTRv with neuropathy (alone or with cardiomyopathy). Recently, the Phase III ATTRACT trial showed that tafamidis decreased the relative risk of mortality in ATTR amyloidosis with cardiomyopathy. The aims of this study were to assess the clinical characteristics of ATTR amyloidosis in a real-life population in comparison to the population included in the ATTRACT trial and to assess the impact of tafamidis on major cardiovascular outcome-free (MCO-free) survival time without cardiac decompensation, heart transplant, or death. From June 2008 to November 2018, 648 patients with ATTR amyloidosis (423 ATTRwt and 225 ATTRv) consecutively referred to the French Referral Center for cardiac amyloidosis were included. 467 (72%) patients matched the inclusion criteria of the ATTRACT study. For the 631 patients with cardiomyopathy, median MCO-free survival time increased with tafamidis treatment ( N = 98): 1565 (1010–2400) days vs. 771 (686–895) days without treatment (log-rank P < 0.001). This beneficial effect was confirmed after considering confounding factors (age at inclusion, Nt-proBNP and amyloidosis type) with a propensity score based on (hazard ratio: 0.546, P = 0.0132). In a large cohort of ATTRwt and ATTRv patients, representative of the inclusion criteria of the ATTRACT trial, the present results confirm the positive impact of tafamidis treatment on preventing the occurrence of cardiovascular outcome in a real-life population.