This summary is based on the publication of Shah SJ et al. - Effect of Tafamidis on Cardiac Function in Patients With Transthyretin Amyloid Cardiomyopathy: A Post Hoc Analysis of the ATTR-ACT Randomized Clinical Trial. JAMA Cardiol. 2023 Nov 15:e234147. doi: 10.1001/jamacardio.2023.4147
Background
Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive and fatal disease caused by the deposition of amyloid fibrils, which consists of misfolded TTR aggregates, in the myocardium. The ATTR-ACT (Tafamidis in Transthyretin Cardiomyopathy Clinical Trial) study showed that tafamidis—a TTR kinetic stabilizer—reduced mortality, CV-related hospitalization and the decline in functional capacity and quality of life in these patients compared with placebo [1]. The next year, the FDA approved tafamidis meglumine 80 mg for ATTR-CM [2]. However, the effect of tafamidis on cardiac function has not been fully characterized.
Aim of the study
In an exploratory, post-hoc analysis of the ATTR-ACT trial, the authors assessed the effect of tafamidis on prognostic echocardiographic measures of cardiac function in patients with ATTR-CM.
Methods
The ATTR-ACT trial was an international, multicenter, double-blind, placebo-controlled phase 3 RCT in which 441 ATTR-CM patients (aged 18–90 years) with a medical history of HF and end-diastolic interventricular septal wall thickness ≥12 mm were included. Participants were randomized to tafamidis meglumine (80 or 20 mg) or placebo for 30 months.
For this pos-hoc analysis, echocardiographic data were available for 436 patients. Based on LVEF at enrollment, patients were categorized into: HFpEF (LVEF ≥50%) (n=220; 50.5%), HFmrEF (LVEF 41%–49%) (n=119; 27.3%), and HFrEF (LVEF ≤40%) (n=97; 22.2%).
Outcomes
Study outcomes were changes from baseline to 30 months in LVEF, LV stroke volume (LVSV), LV global longitudinal strain (LV GLS), ratio of early mitral inflow velocity to septal/early diastolic mitral annular velocity (E/e’), and lateral E/e′ in patients receiving tafamidis 80 mg versus placebo.
In this exploratory, post-hoc analysis of the ATTR-ACT trial, treatment with tafamidis 80 mg attenuated the decline in several LV systolic and diastolic functions over 30 months in ATTR-CM patients compared with placebo. There was no significant difference in the decline in LVEF between the 2 groups.
The authors observed that approximately half of the patients had HFmrEF or HFrEF at enrollment, suggesting that “ATTR-CM should be considered as a possible diagnosis in all patients with HF, regardless of LVEF.” Furthermore, as the 5 echocardiographic parameters studied “have been identified as independent prognostic factors for mortality in patients with ATTR-CM [3,4], [...] the effect of tafamidis on cardiac function in patients with ATTR-CM may underlie improved survival.”
1. Maurer MS, Schwartz JH, Gundapaneni B, et al; ATTR-ACT Study Investigators. Tafamidis treatment for patients with transthyretin amyloid cardiomyopathy. N Engl J Med. 2018;379(11):1007-1016. doi:10.1056/NEJMoa1805689
2. Pfizer. Vyndaqel (tafamidis meglumine) and Vyndamax (tafamidis) prescribing information. Accessed December 4, 2022. https://www.fda.gov/media/126283/download
3. Chacko L, Martone R, Bandera F, et al. Echocardiographic phenotype and prognosis in transthyretin cardiac amyloidosis. Eur Heart J. 2020;41(14):1439-1447. doi:10.1093/eurheartj/ehz905
4. Bukhari S, Bashir Z, Shpilsky D, Eisele YS, Soman P. Abstract 16145: reduced ejection fraction at diagnosis is an independent predictor of mortality in transthyretin amyloid cardiomyopathy. Circulation. 2020;142(suppl 3):A16145-A16145. doi:10.1161/circ.142.suppl_3.16145
Facebook Comments