Clinical characteristics, outcome, and therapeutic effect of tafamidis in wild‐type transthyretin amyloid cardiomyopathy

Abstract

Aims Tafamidis improves prognosis in patients with transthyretin amyloid cardiomyopathy (ATTR‐CM). However, real‐world data on the therapeutic effect of tafamidis are lacking. This study aimed to evaluate the clinical course, outcomes, and effectivity monitoring of the therapeutic effect of tafamidis in patients with ATTR‐CM. Methods and results This is a single‐centre, retrospective observational study. We evaluated the clinical characteristics and outcomes in 125 consecutive patients with wild‐type ATTR‐CM (ATTRwt‐CM) treated with tafamidis (treatment group) and 55 untreated patients (treatment‐naïve group). We monitored the therapeutic effect of tafamidis for 12 months by evaluating serial cardiac biomarker and imaging findings. The treatment group had significantly more favourable outcome in all‐cause mortality and hospitalization due to heart failure than the treatment‐naïve group in both the entire cohort (P < 0.01) and the propensity score‐matched cohort (P < 0.05). Kaplan–Meier survival curves showed that tafamidis treatment significantly reduced all‐cause mortality (P = 0.03, log‐rank test), with the curves diverging after approximately 18 months of treatment in the propensity score‐matched cohort. On inverse probability of treatment weighting analysis, tafamidis treatment showed a reduced all‐cause mortality [hazard ratio (HR), 0.31; 95% confidence interval (CI), 0.11–0.93; P = 0.04]. High‐sensitivity cardiac troponin T (hs‐cTnT) > 0.05 ng/mL, B‐type natriuretic peptide (BNP) > 250 pg/mL, and estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m2 scored 1 point each. Multivariate logistic regression analysis revealed that a high score (2–3 points) was a significantly poor prognostic factor of composite clinical outcomes, including all‐cause death and hospitalization for heart failure (HR, 1.55; 95% CI, 1.22–1.98; P < 0.01) for patients in the treatment group. After 12 months of tafamidis treatment, hs‐cTnT levels decreased significantly [0.054 (0.036–0.082) vs. 0.044 (0.033–0.076); P = 0.002], with no significant changes in BNP levels, echocardiographic parameters, native T1 value, and extracellular volume fraction on cardiac magnetic resonance imaging. Conclusions The prognosis of patients with ATTRwt‐CM treated with tafamidis was more favourable than that of untreated patients. Patient stratification combined with biomarkers (hs‐cTnT, BNP, and eGFR) predicted clinical outcomes. hs‐cTnT may be a useful biomarker for evaluating the therapeutic effect of tafamidis.

Tafamidis treatment in patients with transthyretin amyloid cardiomyopathy: a systematic review and meta-analysis

“…Ten conference abstracts, 8 articles 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 with overlapping data from the ATTR-ACT study, 6 and 4 studies 33 , 34 , 35 , 36 without available data for analysis were excluded. Finally, fifteen articles, 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 19 , 20 , 21 , 22 involving a total of 2765 patients, were included in the meta-analysis. The study and patient characteristics are summarized in Table 1 and Table 2 .…”

“…678 (28.0%) patients died or received heart transplantation in nine studies. 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 In addition, a total of 1060 patients with wild-type ATTR (wtATTR) in 4 articles 7 , 10 , 11 , 13 and 78 patients with hereditary ATTR (hATTR) in 1 article 12 were included for subgroup analysis. A flowchart of the study is shown in Fig.…”

“… 13 2023 Retrospective 842 d 12 Tafamidis Cardiomyopathic All-cause death, heart failure exacerbations Takashio et al. 7 2023 Retrospective 66 d 37.5 ± 18.1 Tafamidis 80 mg/d Cardiomyopathic All-cause death, heart failure hospitalization Rettl et al. 15 2023 Prospective 137 9.5 ± 5.1 b Tafamidis 61 mg/d or 20 mg/d Cardiomyopathic Only include for the analysis of changes in LVEF, IVS, and GLS Chamling et al.…”

“…For the study from Bezard et al., 14 the numbers of endpoints were extracted by survival curves using IPDfromKM. 18 In addition, we conducted propensity score matching (PSM) in two studies 7 , 13 that underwent PSM for inclusion to control baseline differences. Furthermore, four studies, 19 , 20 , 21 , 22 provided as median (range), were converted into mean ± SD for pooled SMDs calculation.…”

“… 5 In the ATTR-ACT trial, tafamidis was reported to be associated with improved survival in patients with ATTR-CM, 6 similar to other observational studies. 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 Moreover, other studies have reported that tafamidis delays structural and functional changes in the left ventricle. 15 , 16 Nevertheless, changes in the left ventricle, following tafamidis treatment, vary within these studies and its efficacy is limited by small sample sizes, low number of events, and short follow-up periods.…”