Tafamidis meglumine 20mg capsules

BackgroundTransthyretin amyloid cardiomyopathy (ATTR-CM) predominantly affects older adults, and tafamidis has proven efficacy in reducing mortality and hospitalizations in this population. However, its clinical benefit in octogenarians remains uncertain due to limited life expectancy, frailty, and other age-related factors. This meta-analysis evaluates the effect of tafamidis in patients aged ≥ 80 years, aiming to address the gap in evidence regarding the therapy's impact in this population.MethodsA systematic review and meta-analysis were conducted by searching PubMed, Embase, and Cochrane databases for studies comparing tafamidis versus control in patients aged ≥ 80 years with transthyretin amyloidosis. The primary outcome was all-cause mortality. Hazard ratios (HRs) were pooled using a random-effects model, and heterogeneity was assessed using I² statistics.ResultsThree studies with a total of 1,866 participants were included (1 randomized controlled trial, 1 prospective cohort, and 1 retrospective study). The majority (77.3%) of patients received tafamidis, and the mean age was 84 years. Tafamidis was associated with a significant reduction in all-cause mortality (HR: 0.51; 95% CI 0.40-0.67; p ConclusionTafamidis significantly reduces all-cause mortality in octogenarian patients with ATTR-CM, supporting its use as a cornerstone therapy in this population. Further randomized controlled trials are needed to validate these findings and optimize treatment strategies in very elderly patients with advanced disease or comorbidities.

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BackgroundWe used network meta-analyses to evaluate the pharmacological interventions for Hereditary Transthyretin-related Amyloidosis with Polyneuropathy (ATTRv-PN).MethodsWe searched Medline, Embase, and Cochrane (June 2025) for randomized trials assessing pharmacological interventions in ATTRv-PN adults. Two reviewers independently screened, extracted data, and assessed risk of bias. Primary efficacy outcomes were mNIS+7 and Norfolk-QoL-DN. Primary safety outcome was serious adverse events (SAE). We used Bayesian hierarchical models. Evidence certainty was assessed using GRADE.ResultsSix trials (n = 989) were included (3 at high-risk of bias). Participant ages and disease duration ranged from 52.8 to 62.0 and 1.4 to 3.9 years, respectively. For mNIS+7, data were available for all interventions except tafamidis. All demonstrated statistically significant improvements versus placebo. Vutrisiran (standardized mean difference [SMD] vs. placebo: -1.66; 95% credible interval [CrI]: -2.13 to -1.17) and patisiran (SMD vs. placebo: -1.56; 95% CrI: -1.88 to -1.25) demonstrated improvements compared with diflunisal, eplontersen, and inotersen. For Norfolk-QoL-DN, data were available for all interventions except diflunisal. All except tafamidis demonstrated statistically significant improvements versus placebo. Patisiran (MD vs. placebo: -17.39; 95% CrI: -23.22 to -11.57), vutrisiran (MD vs. placebo: -16.99; 95% CrI: -25.24 to -8.72), and eplontersen (MD vs. placebo: -15.56; 95% CrI: -21.97 to -9.15) demonstrated improvements compared with tafamidis. For SAE, there were no differences between active interventions versus placebo. Confidence in the evidence varied from very low to moderate.ConclusionGene-silencing therapies were more efficacious, although these findings should be regarded as hypothesis-generating given the scarcity of data, lack of head-to-head trials, and clinical heterogeneity across trials.

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Background Transthyretin amyloid cardiomyopathy (ATTR-CM) has recently gained recognition as a rare and fatal disease. Tafamidis, a first-in-class transthyretin stabilizer, has emerged as a promising agent for attenuating disease progression. Nevertheless, how tafamidis alters clinical and imaging parameters remains unclear. Objectives This systemic review and meta-analysis aimed to investigate how tafamidis remodels the myocardium and influences the disease trajectory of ATTR-CM. Methods PubMed, EMBASE, and the Cochrane Library were searched for literature from inception to February 2024 which reported either the effects of tafamidis treatment or natural course of ATTR-CM. Outcomes of interests were all clinical and imaging parameters available from at least 2 independent studies. Results We identified 30 studies comprising 2,973 participants with ATTR-CM. Pooling all studies with outcomes of both tafamidis and placebo, tafamidis significantly reduced all-cause mortality (OR: 0.19; 95% CI: 0.07 to 0.56) and cardiovascular death (OR: 0.08; 95% CI: 0.02-0.30). Tafamidis also ameliorated the deterioration of 6-minute walk distance (standardized mean difference [SMD] 0.04 vs. −0.29, P = 0.002) and serum N-terminal pro-B-type natriuretic peptide level (SMD: -0.03 vs 0.41, P < 0.001). Regarding imaging parameters, better global longitudinal strain on echocardiography (SMD: 0.06 vs 0.50, P = 0.003), heart to contralateral ratio (SMD: −0.23 vs. −1.17, P = 0.037) on technetium-99m pyrophosphate scintigraphy, extracellular volume (P = 0.003), left (P < 0.001) and right (P = 0.001) ventricular ejection fraction, and right atrium area (P = 0.033) on cardiac magnetic resonance imaging were observed after tafamidis treatment. Conclusions Tafamidis improves clinical outcomes and limits the progression of cardiac remodeling in ATTR-CM.

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Abstract Aims Transthyretin cardiac amyloidosis (ATTR-CA) is an important cause of heart failure (HF). Several therapies demonstrated an efficacy in reducing hard and surrogate endpoints. We compared the relative efficacy of therapies evaluated in completed phase III trials. Methods and results We conducted a network meta-analysis using data from ATTR-ACT, ATTRIBUTE-CM, APOLLO-B, and HELIOS-B. The primary endpoint was a composite of all-cause mortality and cardiovascular hospitalizations. Secondary endpoints were changes in the 6-minute walk distance (6MWD) and Kansas City Cardiomyopathy Questionnaire-Overall Summary (KCCQ-OS) scores. For the primary endpoint, tafamidis and vutrisiran demonstrated a significant survival benefit over placebo; acoramidis approached significance. In indirect comparisons, there was no clear evidence of a larger absolute risk reduction for any drug. Tafamidis was associated with the lowest risk for the primary endpoint (surface under the cumulative ranking, SUCRA 82%), followed by vutrisiran monotherapy (70%). Regarding changes in 6MWD, tafamidis and acoramidis had the highest SUCRA curve values (97% and 69%, respectively). For KCCQ-OS changes, tafamidis also had the highest SUCRA (87%), followed by acoramidis (79%) and vutrisiran monotherapy (67%). When the ATTR-ACT trial was excluded from the analysis, vutrisiran monotherapy consistently showed the highest probability of being ranked better than other treatments in terms of primary end-point. Conclusion Although differences in trial design and study populations complicate direct efficacy comparisons, tafamidis demonstrated the highest efficacy in improving survival, reducing cardiovascular hospitalizations, and enhancing functional capacity and quality of life in patients with ATTR-CA, but also vutrisiran and acoramidis emerged as viable options.

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