Early Experience of Tafamidis Treatment in Japanese Patients With Wild-Type Transthyretin Cardiac Amyloidosis From the Kochi Amyloidosis Cohort

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.

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“…Ochi et al 17 . reported the early experience of tafamidis in patients with ATTRwt‐CM in Kochi University ( n = 38).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2023

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“…Tafamidis showed a decrease in CV mortality due to heart failure in the study by Ochi et al ., while in the ATTR-ACT trial, it did not exhibit any reduction 6 , 8 . However, according to the fixed effect model, the comprehensive results from the forest plot appeared to give a remarkable reduction in CV mortality with an overall effect estimate (OR 0.72; 95% CI: [0.56–0.92], P =0.009, I 2 =88%; Fig.…”

Section: Resultsmentioning

confidence: 74%

“…1 . 1 ) 6 , 8 . To better characterize this outcome, a subgroup analysis was conducted for CV mortality due to heart failure (OR 0.89; 95% CI: [0.63–1.25], P =0.50, I 2 =93%; Fig.…”

Section: Resultsmentioning

confidence: 99%

Efficacy of tafamidis in transthyretin amyloid cardiomyopathy: a systematic review and meta-analysis

Sukaina,

Rehman,

Waheed

et al. 2023

Annals of Medicine &Amp; Surgery

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In May 2019, FDA-approved Tafamidis as the first conservative management of ATTR-CM. Our aim in conducting this systematic review and meta-analysis was to assess the efficacy of Tafamidis on patients with ATTR-CM. For that purpose, we thoroughly searched PubMed, Science Direct, and Clinical trails.gov by using appropriate search strategy and following predefined inclusion and exclusion criteria which retrieved 235 articles initially. Of which 2 randomized controlled trials (RCTs) and 1 observational study matched our inclusion criteria. A total of 876 patients are included in this analysis. Based on results, Tafamidis significantly reduced cardiovascular (CV) mortality in the ATTR-ACT trial and Ochi et al., (OR 0.58; 95% CI: [0.41, 0.83], P = 0.003, I² = 87%. A subgroup analysis was conducted for CV mortality due to heart failure (OR 0.89; 95% CI: [0.63, 1.25], P = 0.50, I² = 93%. The results exhibits that Tafamidis reduced all-causes of mortality (OR 0.45; 95% CI: [0.32, 0.64], P = < 0.00001, I²= 22%). Furthermore, mortality remained statistically insignificant in patients with heart transplants (OR 1.18; 95% CI: [0.52, 2.70], P = 0.70, I²= 0%) and patients with cardiac mechanical assist devices (OR 4.15; 95% CI: [0.48, 35.66], P = 0.20, I²= 0%). This meta-analysis suggests that Tafamidis is a safe and efficient drug to use in patients with ATTR-CM and can possess the potential to be a milestone in enhancing the conservative management of the patients.

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“…Further, we consider patient selection before treatment initiation to be an important point for treatment efficacy. Regarding the administration of tafamidis, Ochi, et al 19) emphasized the importance of patient selection and confirmed that the disease should not be advanced in patients. Our patients may have been in the advanced stages of ATTR-CM and frailty, which may have diminished the effect of tafamidis.…”

Section: Discussionmentioning

confidence: 99%

Changes in Exercise Tolerance over Time in Patients with Transthyretin Amyloidosis Cardiomyopathy Treated with Tafamidis

2023

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Tafamidis improves the prognosis of patients with transthyretin amyloidosis cardiomyopathy (ATTR-CM). Additionally, it delays the decline in exercise tolerance, as observed in the six-minute walking test. However, the changes in cardiopulmonary function over time based on cardiopulmonary exercise tests are unclear. Thus, this preliminary study investigated the changes in exercise tolerance after one year of tafamidis treatment using cardiopulmonary exercise testing. Eight patients with ATTR-CM (average age: 77 years; male: n = 7) underwent cardiopulmonary exercise testing at baseline and after one year of tafamidis treatment. All eight patients completed a one-year follow-up. At baseline, the anaerobic threshold oxygen uptake (AT !O2: 10.9 ± 1.5) and peak !O2 (14.3 ± 3.0 mL/kg/minute) indicated relatively favorable exercise capacity; however, the minute ventilation/ carbon dioxide production ( !E/!CO2 slope), which indicates effective ventilation, showed poor performance (33.7 ± 12.8). One year after tafamidis treatment, frailty, as assessed by the Clinical Frailty Scale, had progressed in seven of eight patients (88%) (P < 0.01), and AT !O2 and peak !O2 were significantly reduced (19.2% and 22.3%, respectively; P < 0.05). The !E/!CO2 slope and peak O2 pulse decreased nonsignificantly by approximately 20% (P = 0.47, and P = 0.16, respectively). Further, the structure of the ventricles and atrium and the left ventricle ejection fraction on echocardiography did not change. Thus, exercise tolerance in patients with ATTR-CM was reduced after one year despite tafamidis administration. Not only ATTR-CM progression, but also frailty progression may influence this decrease in exercise tolerance. A comprehensive approach, including tafamidis administration and cardiac rehabilitation, is required for further improvement in the exercise capacity of patients with ATTR-CM.

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Early Experience of Tafamidis Treatment in Japanese Patients With Wild-Type Transthyretin Cardiac Amyloidosis From the Kochi Amyloidosis Cohort

Cited by 20 publications

References 19 publications

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

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

Efficacy of tafamidis in transthyretin amyloid cardiomyopathy: a systematic review and meta-analysis

Changes in Exercise Tolerance over Time in Patients with Transthyretin Amyloidosis Cardiomyopathy Treated with Tafamidis

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