Tafamidis 61mg capsules

Tafamidis was FDA-approved for Transthyretin cardiomyopathy (ATTR-CM) due to its demonstrated reduction in mortality and hospitalizations. 976 studies from PubMed and Embase were screened. Seven studies were included that compared tafamidis treatment with no tafamidis for ATTR-CM. The mantel-Haenszel method was used for binary outcomes, and Hedges’ g was used for continuous outcomes. Tafamidis was associated with decreased odds of mortality (OR 0.55, 95 % CI 0.42-0.73, I 2 =41 %, p<0.0001) and reduced CHF exacerbations (OR 0.71, 95 % CI 0.51-0.99, I 2 = 0 %, p= 0.04). While, CHF related hospitalizations (OR 0.35, 95 % CI 0.07-1.67, I2= 87 %, p= 0.19), atrial arrhythmias (OR 0.98, 95 % CI 0.67-1.42, I 2 = 0 %, p= 0.9), change in left ventricular ejection fraction (SMD 0.87, 95 % CI -0.37-2.11, I 2 =98 %, p= 0.17), left ventricular end-diastolic diameter from baseline (SMD -0.12, 95 % CI -0.41-0.18, I 2 = 0 %, p= 0.4), interventricular septal thickness from baseline (SMD -0.7, 95 % CI -1.57-0.17, I 2 = 96 %, p= 0.11) were not statistically different for tafamidis compared to no tafamidis for ATTR-CM. Tafamidis treatment in ATTR-CM is associated with reduced all-cause mortality and a lower incidence of CHF exacerbations. These observations are consistent with the ATTRACT trial, which supports the efficacy of tafamidis in treating ATTR-CM.

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BACKGROUND AND AIMS: In real-world, wild-type transthyretin cardiomyopathy is increasingly diagnosed in patients ≥ 80 years old (octogenarians), although being underrepresented in randomized clinical trials. Specific data on natural course and outcome under tafamidis treatment in octogenarians are therefore scarce. The impact of tafamidis treatment on mortality in real-world wild-type transthyretin cardiomyopathy octogenarians was studied. METHODS: An international, multicentre cohort study of 710 consecutive wild-type transthyretin cardiomyopathy patients with mean follow-up of 2.2 ± 1.8 years for all-cause mortality endpoint was performed. RESULTS: The cohort consisted of 58.5% (415/710) octogenarians (85 ± 4 years, 74.2% male). Before tafamidis availability, natural course in octogenarians (148/257) vs. non-octogenarians (109/257) was poor, with 16% 1-year and 71% 5-year mortality vs. 8% and 47%, respectively (P < .001). Since tafamidis availability, 70.1% (253/361) octogenarians were initiated on tafamidis vs. 83.7% (231/276) non-octogenarians (P < .001). Tafamidis discontinuation was similar (octogenarians 10.3% and non-octogenarians 7.4%; P = .260). Overall tafamidis treated vs. untreated octogenarians had better unadjusted survival (P < .001), with 5% 1-year and 24% 3-year mortality. Tafamidis treatment associated with lower mortality after propensity score matching on baseline variables, including age, National Amyloidosis Centre stage, and New York Heart Association class in on average 394 subjects [hazard ratio (HR) = 0.53, 95% confidence interval (CI) 0.34-0.84, P = .007], also in octogenarians (HR = 0.57, 95% CI 0.33-1.01, P = .053). Neither age at diagnosis (P = .217) nor at treatment initiation (P = .154) interacted with tafamidis mortality benefit. Octogenarians had poorer survival despite tafamidis, when initiated at ≥90 years (HR = 3.3, 95% CI 1.10-9.53, P = .033) and National Amyloidosis Centre Stage ≥3 (HR = 2.4, 95% CI 0.87-6.46, P = .090). CONCLUSIONS: Real-world tafamidis treatment improves survival without age affecting treatment efficacy, although mortality remains considerable in octogenarians.

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AIMS: Tafamidis reshaped the treatment paradigm in transthyretin amyloid cardiomyopathy (ATTR-CM) based on a phase-3 randomized controlled trial, but real-world data on its use remain limited. This study aimed to assess in a large, contemporary, real-world cohort of patients with wild-type ATTR-CM (ATTRwt-CM) (i) the clinical phenotype of patients receiving tafamidis, and (ii) the association of tafamidis with survival using propensity-matched observational data. METHODS AND RESULTS: Data of patients diagnosed with ATTRwt-CM (January 2017 to June 2023) from 19 Italian centres were analysed. A propensity score (PS) reflecting the likelihood of being treated with tafamidis for each patient was determined using four variables that were significantly different among the two groups: age, New York Heart Association (NYHA) class, National Amyloidosis Centre (NAC) stage and mineralocorticoid receptor antagonists (MRAs). The primary outcome was all-cause mortality. The study comprised 1556 ATTRwt-CM patients: 965 (62%) patients initiated on tafamidis by June 2023 and 591 (38%) patients never treated with disease-modifying therapy. Tafamidis-treated patients were older, exhibited a lower NYHA class and NAC stage, and were more often treated with MRAs compared to untreated patients. The PS-matched cohort comprised 426 patients treated with tafamidis and 426 PS-matched untreated patients (mean age 78.9 ± 5.0 years, 88.3% men, 12.9% in NYHA class III). Adequacy of matching was verified (standardized differences: <0.20 between groups). Over 25 months (interquartile range: 15-40), treatment with tafamidis was associated with lower rates of all-cause mortality (hazard ratio 0.55, 95% confidence interval 0.39-0.77, p = 0.001) across the spectrum of NAC disease stages (p-interaction = 0.94). CONCLUSIONS: In this large, contemporary, real-world cohort of patients with ATTRwt-CM, predominantly in NYHA class I or II, treatment with tafamidis was consistently associated with a significantly lower risk of all-cause mortality.

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Transthyretin amyloid cardiomyopathy (ATTR-CM) is increasingly recognized as a cause of heart failure with preserved ejection fraction in older adults. Tafamidis, a transthyretin stabilizer, is the first disease-modifying therapy approved for ATTR-CM. Although its efficacy was demonstrated in the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT) trial, real-world data are essential to evaluate its effectiveness across broader and more diverse patient populations. This review synthesizes real-world evidence on tafamidis, including patient characteristics, diagnostic and therapeutic delays, and clinical outcomes such as mortality, hospitalization, cardiac biomarker trends, imaging findings, and functional capacity. Compared with clinical trial participants, real-world patients are generally older, often present with more advanced disease, and initiate treatment later in the disease course. Nevertheless, observational studies from Japan and other countries consistently show that tafamidis is associated with improved survival, reduced heart failure hospitalizations, stabilization of cardiac structure and biomarkers, and preservation of physical function - especially when therapy is started early. Accumulating such data will be crucial for optimizing patient care, particularly in the context of future treatment strategies involving emerging agents such as a next-generation oral transthyretin stabilizer and a subcutaneously administered RNA interference therapeutic. This review aims to bridge the gap between clinical trial findings and routine practice, supporting informed decision-making in the management of this progressive and underdiagnosed condition.

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BACKGROUND: Tafamidis improved survival and decreased cardiovascular hospitalizations in the ATTR-ACT trial. Due to improved recognition and earlier diagnosis, the epidemiology of transthyretin amyloid cardiomyopathy (ATTR-CM) is rapidly evolving. OBJECTIVES: The authors sought to evaluate the contemporary long-term outcomes of patients with ATTR-CM treated with tafamidis. METHODS: Patients with ATTR-CM who received at least 1 dose of tafamidis between 2018 and 2021 at 5 amyloidosis centers in the United States were enrolled. Primary outcome was all-cause mortality. RESULTS: Among 624 patients, mean age was 76.9 ± 8.4 years, 12.5% were female, 17.5% were Black, and 17.5% had variant ATTR-CM. At the time of tafamidis start, 52% had NYHA functional class II, 34% had NYHA functional class III, 40% were in National Amyloidosis Center (NAC) Stage ≥II, 38% were in Columbia Stage ≥II, and the median NT-proBNP level was 1,914 (Q1-Q3: 957-3914) pg/mL. Over a median follow-up of 43.2 months (Q1-Q3: 25.2-52.8 months), 241 patients (38.6%) died. The probability of freedom from death at 65 months was 54.1% (95% CI: 47.4%-60.4%). Similarly, restricting the cohort to patients who received tafamidis within 6 months of their ATTR-CM diagnosis (n = 397, 63.6%) showed similar results, with a survival probability of 49.6% (95% CI: 37.6%-60.5%) at 65 months. CONCLUSIONS: In a contemporary cohort of tafamidis-treated patients with ATTR-CM, 39% of patients died over a median of 43 months. Further work is needed to improve our understanding of ATTR-CM, its natural history, and how to further improve survival and prevent progression of heart failure.

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