Transthyretin (TTR) protein, synthesised by the liver, exists in a tetrameric structure. If the TTR tetramer is unstable, it can dissociate into monomers that misfold and aggregate into amyloid fibrils. Transthyretin-mediated amyloidosis with cardiomyopathy (ATTR-CM) is a life-threatening disease characterised by the accumulation of these TTR amyloid fibrils in the myocardium.1
The discovery that an amino acid substitution in TTR from thyroxine to methionine can inhibit dissociation of the tetramer led to the development of tafamidis, a non-steroidal anti-inflammatory drug that stabilises TTR by selectively binding to thyroxine-binding sites.1
Studies have since shown that tafamidis is an efficacious treatment for ATTR-CM, associated with a reduction in mortality and cardiovascular-related hospitalisations compared with placebo.1 In a poster presented at this year’s American College of Cardiology Scientific Sessions, Dr Abdullah Sarkar looked to answer whether this benefit extends to patients ≥80 years.
Two subgroups (patients aged ≥85 years and patients aged <85 years) were identified within the multicentre, prospectively collected Cleveland Clinic Amyloid Registry and each split into ‘on-tafamidis’ and ‘no-tafamidis’ subgroups. The study excluded those patients with NYHA class IV symptoms at diagnosis, patients who had received cardiac transplant or left ventricular assist devices and patients taking other disease-modifying agents.
As expected, patients receiving tafamidis had a significantly higher survival probability than the patients not receiving tafamidis in the overall population (median follow-up 18.7 months and 16.4 months, respectively). Interestingly, this benefit was also observed in the ≥80 years subgroup (median follow-up 16.2 months with tafamidis and 15.0 months without tafamidis).
|HR: 0.21; 95% CI: 0.13-0.34, p<0.001|
|≥80 years subgroup||55.2%
|HR: 0.13; 95% CI: 0.07-0.28|
Patients were then further stratified by their Gillmore stage, a prognostic staging system based on patients NT-proBNP levels and eGFR, where higher stage indicates worse prognosis:2
This analysis found that the probability of survival in patients aged ≥80 years treated with tafamidis is higher in those with Gillmore stage I and II than those with Gillmore stage III, suggesting that tafamidis may be most beneficial in this age group when given to those with less severe disease.
CI: confidence interval; eGFR: estimated glomerular filtration rate; HR: hazard ratio; NT-proBNP: N-terminal pro B-type natriuretic peptide; NYHA: New York Heart Association
Based on: Sarkar A, Miranda D et al. Vutrisiran efficacy and safety at 18 months: results from the HELIOS-A phase III trial Analysis of the Cleveland Clinic Amyloid Registry. Presented at ACC.22, 2-4 April 2022, Washington, DC, US
The benefits of tafamidis: is there an age limit?
Top image: Design Cells
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