966 results on '"tafamidis"'
Search Results
2. Disease‐modifying therapies for amyloid transthyretin cardiomyopathy: Current and emerging medications.
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Hellenbart, Erika L., Ipema, Heather J., Rodriguez‐Ziccardi, Mary C., Krishna, Hema, and DiDomenico, Robert J.
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AMYLOID beta-protein , *RANDOMIZED controlled trials , *GENOME editing , *ANTISENSE RNA , *TRANSTHYRETIN - Abstract
Transthyretin amyloidosis (ATTR) is a rare disease that results in amyloid fibril misfolding and deposition in multiple organs, including the heart, leading to the development of ATTR cardiomyopathy (ATTR‐CM), which is associated with poor outcomes. In the last decade, several disease‐modifying medications are in advanced stages of clinical development or have been approved to treat ATTR‐CM. The purpose of this review is to critically evaluate clinical trial data investigating the use of approved and investigational medications for the treatment of ATTR‐CM. We performed a comprehensive literature search via PubMed and EMBASE to identify randomized controlled trials evaluating medications for the treatment of ATTR‐CM published through August 2024. This narrative review describes the pathophysiology of ATTR‐CM, highlights important screening and diagnostic work‐up, and summarizes the existing clinical evidence resulting from our literature search. Several classes of disease‐modifying medications are in development for ATTR‐CM. The tetramer stabilizers and transthyretin silencers have proven to be the most effective therapies to date. Tafamidis and acoramidis are currently approved for ATTR‐CM while vutrisiran approval for ATTR‐CM may be forthcoming. Other disease‐modifying medication classes in development include antisense oligonucleotides, gene editing therapies, and monoclonal antibodies. However, several unmet needs exist including the lack of cost‐effectiveness due to the extremely high acquisition costs of these medications. Disease‐modifying medications approved and in development to treat ATTR‐CM offer hope for patients with this disease, but their lack of affordability is the biggest barrier to their use. [ABSTRACT FROM AUTHOR] more...
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- 2024
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Catalog
3. From transthyretin cardiac amyloidosis diagnosis to tafamidis treatment: Association of drop-off with patient sociodemographic characteristics.
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Walenczyk, Kristie M, Singh, Avinainder, Tong, Kimhouy, Burg, Matthew M, and Miller, Edward J
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HETEROCYCLIC compounds , *CARDIAC amyloidosis , *RESEARCH funding , *SEX distribution , *AGE distribution , *RACE , *SOCIODEMOGRAPHIC factors , *SERUM albumin , *RADIONUCLIDE imaging , *SOCIAL isolation - Abstract
Purpose Compared to estimated population prevalence rates, relatively few patients at risk are diagnosed with and treated for transthyretin cardiac amyloidosis (ATTR-CA). Where along the clinical pathway patient drop-off occurs, as well as the association of drop-off with patient sociodemographic characteristics, remains unknown. Methods Using data from a healthcare system–wide cardiovascular imaging repository and specialty pharmacy, we characterized the clinical pathway from diagnosis with pyrophosphate scintigraphy (PYP) to tafamidis prescription, initiation, and adherence. Standardized differences (d values of ≥0.20, indicating at least a small effect size) were used to compare sociodemographics (age, sex, race, Area Deprivation Index) among patients with PYP-identified ATTR-CA by tafamidis prescription status and among patients prescribed tafamidis by initiation status. Tafamidis adherence was measured with the proportion of days covered (PDC). Results Of 97 patients with ATTR-CA, 58.8% were prescribed tafamidis, with 80.7% of those initiating therapy. Patients with ATTR-CA prescribed tafamidis were younger than those not prescribed tafamidis (d = –0.30). Utilization of a specialty pharmacy resulted in enrichment of treatment in subgroups traditionally undertreated in cardiovascular medicine, with higher rates of tafamidis initiation among women (100% initiation), patients of Black/African American race (d = 0.40), and those living in more economically disadvantaged areas (d ≥ 0.30). Adherence was high (PDC of >80%) in 88.4% of those initiating tafamidis. Conclusion These findings highlight the tremendous opportunity for more robust ATTR-CA clinical programs, identifying potential patient subgroups that should be targeted to reduce disparities. For patients diagnosed with ATTR-CA, utilization of a specialty pharmacy process appears to ensure equitable provision of tafamidis therapy. [ABSTRACT FROM AUTHOR] more...
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- 2024
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4. RESHAPING TREATMENT PARADIGMS: Despite uncertainty around who will sit in The White House in January and what ramifications they may bring, the industry's pipeline remains flush with many late-stage therapies showing promising data and transformative potential
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Fernando, Surani
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Merck & Company Inc. ,Johnson & Johnson ,Credit Suisse Group AG ,Novo Nordisk A/S ,Eli Lilly and Co. ,Sanofi S.A. ,Hemlibra (Medication) ,Tremfya (Medication) ,Financial services industry ,Ezetimibe ,Sitagliptin ,Guselkumab ,Brand equity ,Type 2 diabetes ,Patient compliance ,Tafamidis ,Financial services ,Pharmaceutical industry ,Biological products industry ,Semaglutide - Abstract
* As another U.S. election approaches and uncertainty looms over the biopharma world, the horizon remains bright with late-stage therapies showing promising results and transformative potential. Amid the evolving landscape, [...] more...
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- 2024
5. Tafamidis medication adherence and persistence in patients with transthyretin amyloid cardiomyopathy in Japan
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Takao Kato, Monica Ines, Masatoshi Minamisawa, Darrin Benjumea, Denis Keohane, Jose Alvir, Ruth Kim, Yong Chen, Telma Peixoto, Matthew Kent, Jenifer Wogen, Tomonori Ishii, Aaron Crowley, Toshiya Sugino, and Yasuhiro Izumiya more...
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ATTR‐CM ,Cardiomyopathy ,Tafamidis ,Adherence ,Persistence ,Japan ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Abstract Aims This study aimed to describe baseline characteristics and adherence among patients with transthyretin amyloid cardiomyopathy (ATTR‐CM) treated with tafamidis (VYNDAQEL®) in Japan using the Japanese Medical Data Vision (MDV) database. Methods and results This study was a non‐interventional, retrospective cohort study of adult (≥18 years old) patients in the Japanese MDV claims database diagnosed with ATTR‐CM and with at least two tafamidis prescriptions of dose strength 4 × 20 mg/day between 1 March 2019 and 31 August 2021. The date of the first prescription was defined as the index date, with follow‐up time defined as the time between the first and last prescription plus the days' supply from the last refill. Baseline characteristics were assessed during a 12 month pre‐index period. Adherence was measured using two metrics: (i) the modified medication possession ratio (mMPR), calculated by taking the sum of days supplied for all fills within the follow‐up period, divided by the number of days of follow‐up, and reported as a percentage, with patients classified as adherent with an mMPR of ≥80%, and (ii) the proportion of days covered (PDC), calculated by taking the total number of days' supply dispensed during the follow‐up period divided by the number of days of follow‐up, adjusting for any days' supply overlap. A total of 210 patients were identified; the mean (standard deviation) age of the cohort was 77 (5.9) years, and the majority (89%) were male. The most common baseline cardiovascular comorbidities were heart failure (85%), ischaemic heart disease (66%), hypertensive diseases (49%), and diabetes (35%); 75% of patients received heart failure medications in the 12 months prior to index, with the most common being beta‐blockers (49%), diuretics (48%), angiotensin receptor blockers (30%), angiotensin‐converting enzyme inhibitors (22%), and sodium–glucose cotransporter‐2 inhibitors (8.1%). Over an average 14 month follow‐up, mean mMPR was 96% with a median of 100% [inter‐quartile range (IQR): 97–101%]; 93% of patients were adherent (defined as an mMPR ≥ 80%). In the same follow‐up period, mean PDC was 93.6% with a median of 99% (IQR: 93–100%). Persistence was high with 78% of patients having a 0 day gap between prescription refills. Conclusions This study found high adherence rates to tafamidis in this real‐world Japanese patient population. Adherence rates in this study were similar to those reported by the tafamidis clinical trial and a previously published US commercial claims adherence analysis. Further studies should be conducted to assess the impact of real‐world adherence on real‐world outcomes. more...
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- 2024
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6. Impact of tafamidis on myocardial function and CMR tissue characteristics in transthyretin amyloid cardiomyopathy
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Stephan Dobner, Benedikt Bernhard, Lorenz Ninck, Monika Wieser, Adam Bakula, Andreas Wahl, Valentin Köchli, Giancarlo Spano, Martina Boscolo Berto, Elena Elchinova, Yasaman Safarkhanlo, Stefan Stortecky, Jonathan Schütze, Isaac Shiri, Lukas Hunziker, and Christoph Gräni more...
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Cardiac amyloidosis ,Cardiac magnetic resonance imaging ,ECV ,Feature tracking ,GLS ,Tafamidis ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Abstract Aims Tafamidis improves clinical outcomes in transthyretin amyloid cardiomyopathy (ATTR‐CM), yet how tafamidis affects cardiac structure and function remains poorly described. This study prospectively analysed the effect of tafamidis on 12‐month longitudinal changes in cardiac structure and function by cardiac magnetic resonance (CMR) compared with the natural course of disease in an untreated historic control cohort. Methods and results ATTR‐CM patients underwent CMR at tafamidis initiation and at 12 months. Untreated patients with serial CMRs served as reference to compare biventricular function, global longitudinal strain (GLS), LV mass and extracellular volume fraction (ECV). Thirty‐six tafamidis‐treated (n = 35; 97.1% male) and 15 untreated patients (n = 14; 93.3% male) with a mean age of 78.3 ± 6.5 and 76.9 ± 6.5, respectively, and comparable baseline characteristics were included. Tafamidis was associated with preserving biventricular function (LVEF (%): 50.5 ± 12 to 50.7 ± 11.5, P = 0.87; RVEF (%): 48.2 ± 10.4 to 48.2 ± 9.4, P = 0.99) and LV‐GLS (−9.6 ± 3.2 to −9.9 ± 2.4%; P = 0.595) at 12 months, while a significantly reduced RV‐function (50.8 ± 7.3 to 44.2 ± 11.6%, P = 0.028; P (change over time between groups) = 0.032) and numerically worsening LVGLS (−10.9 ± 3.3 to −9.1 ± 2.9%, P = 0.097; P (change over time between groups) = 0.048) was observed without treatment. LV mass significantly declined with tafamidis (184.7 ± 47.7 to 176.5 ± 44.3 g; P = 0.011), yet remained unchanged in untreated patients (163.8 ± 47.5 to 171.2 ± 39.7 g P = 0.356, P (change over time between groups) = 0.027). Irrespective of tafamidis, ECV and native T1‐mapping did not change significantly from baseline to 12‐month follow‐up (P > 0.05). Conclusions Compared with untreated ATTR‐CM patients, initiation of tafamidis preserved CMR‐measured biventricular function and reduced LV mass at 12 months. ECV and native T1‐mapping did not change significantly comparable to baseline in both groups. more...
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- 2024
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7. Right ventricular myocardial biopsy with a guiding catheter for conduction system pacing during pacemaker implantation revealed transthyretin cardiac amyloidosis
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Kei Morishita, MD, Katsuhito Fujiu, MD, PhD, Kenichiro Yamagata, MD, PhD, Eisuke Amiya, MD, PhD, and Norihiko Takeda, MD, PhD
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Transthyretin cardiac amyloidosis ,Myocardial biopsy ,Preshaped guiding catheter ,Pacemaker implantation ,Tafamidis ,Left ventricular hypertrophy ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Published
- 2024
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8. Monitoring the Efficacy of Tafamidis in ATTR Cardiac Amyloidosis by MRI-ECV: A Systematic Review and Meta-Analysis
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Shingo Kato, Mai Azuma, Nobuyuki Horita, and Daisuke Utsunomiya
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cardiac amyloidosis ,cardiac MRI ,extracellular volume fraction ,tafamidis ,meta-analysis ,Computer applications to medicine. Medical informatics ,R858-859.7 - Abstract
Background: The usefulness of monitoring treatment effect of tafamidis using magnetic resonance imaging (MRI) extracellular volume fraction (ECV) has been reported. Objective: we conducted a meta-analysis to evaluate the usefulness of this method. Methods: Data from 246 ATTR-CMs from six studies were extracted and included in the analysis. An inverse variance meta-analysis using a random effects model was performed to evaluate the change in MRI-ECV before and after tafamidis treatment. The analysis was also performed by classifying the patients into ATTR-CM types (wild-type or hereditary). Results: ECV change before and after tafamidis treatment was 0.33% (95% CI: −1.83–2.49, I2 = 0%, p = 0.76 for heterogeneity) in the treatment group and 4.23% (95% CI: 0.44–8.02, I2 = 0%, p = 0.18 for heterogeneity) in the non-treatment group. The change in ECV before and after treatment was not significant in the treated group (p = 0.76), but there was a significant increase in the non-treated group (p = 0.03). There was no difference in the change in ECV between wild-type (95% CI: −2.65–3.40) and hereditary-type (95% CI: −9.28–4.28) (p = 0.45). Conclusions: The results of this meta-analysis suggest that MRI-ECV measurement is a useful imaging method for noninvasively evaluating the efficacy of tafamidis treatment for ATTR-CM. more...
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- 2024
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9. Impact of tafamidis on myocardial function and CMR tissue characteristics in transthyretin amyloid cardiomyopathy.
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Dobner, Stephan, Bernhard, Benedikt, Ninck, Lorenz, Wieser, Monika, Bakula, Adam, Wahl, Andreas, Köchli, Valentin, Spano, Giancarlo, Boscolo Berto, Martina, Elchinova, Elena, Safarkhanlo, Yasaman, Stortecky, Stefan, Schütze, Jonathan, Shiri, Isaac, Hunziker, Lukas, and Gräni, Christoph more...
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CARDIAC magnetic resonance imaging ,GLOBAL longitudinal strain ,CARDIAC amyloidosis ,TRANSTHYRETIN ,AMYLOID - Abstract
Aims: Tafamidis improves clinical outcomes in transthyretin amyloid cardiomyopathy (ATTR‐CM), yet how tafamidis affects cardiac structure and function remains poorly described. This study prospectively analysed the effect of tafamidis on 12‐month longitudinal changes in cardiac structure and function by cardiac magnetic resonance (CMR) compared with the natural course of disease in an untreated historic control cohort. Methods and results: ATTR‐CM patients underwent CMR at tafamidis initiation and at 12 months. Untreated patients with serial CMRs served as reference to compare biventricular function, global longitudinal strain (GLS), LV mass and extracellular volume fraction (ECV). Thirty‐six tafamidis‐treated (n = 35; 97.1% male) and 15 untreated patients (n = 14; 93.3% male) with a mean age of 78.3 ± 6.5 and 76.9 ± 6.5, respectively, and comparable baseline characteristics were included. Tafamidis was associated with preserving biventricular function (LVEF (%): 50.5 ± 12 to 50.7 ± 11.5, P = 0.87; RVEF (%): 48.2 ± 10.4 to 48.2 ± 9.4, P = 0.99) and LV‐GLS (−9.6 ± 3.2 to −9.9 ± 2.4%; P = 0.595) at 12 months, while a significantly reduced RV‐function (50.8 ± 7.3 to 44.2 ± 11.6%, P = 0.028; P (change over time between groups) = 0.032) and numerically worsening LVGLS (−10.9 ± 3.3 to −9.1 ± 2.9%, P = 0.097; P (change over time between groups) = 0.048) was observed without treatment. LV mass significantly declined with tafamidis (184.7 ± 47.7 to 176.5 ± 44.3 g; P = 0.011), yet remained unchanged in untreated patients (163.8 ± 47.5 to 171.2 ± 39.7 g P = 0.356, P (change over time between groups) = 0.027). Irrespective of tafamidis, ECV and native T1‐mapping did not change significantly from baseline to 12‐month follow‐up (P > 0.05). Conclusions: Compared with untreated ATTR‐CM patients, initiation of tafamidis preserved CMR‐measured biventricular function and reduced LV mass at 12 months. ECV and native T1‐mapping did not change significantly comparable to baseline in both groups. [ABSTRACT FROM AUTHOR] more...
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- 2024
- Full Text
- View/download PDF
10. Tafamidis medication adherence and persistence in patients with transthyretin amyloid cardiomyopathy in Japan.
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Kato, Takao, Ines, Monica, Minamisawa, Masatoshi, Benjumea, Darrin, Keohane, Denis, Alvir, Jose, Kim, Ruth, Chen, Yong, Peixoto, Telma, Kent, Matthew, Wogen, Jenifer, Ishii, Tomonori, Crowley, Aaron, Sugino, Toshiya, and Izumiya, Yasuhiro more...
- Subjects
PATIENT compliance ,ANGIOTENSIN-receptor blockers ,HEART failure patients ,HEART diseases ,DATABASES ,HEART failure - Abstract
Aims: This study aimed to describe baseline characteristics and adherence among patients with transthyretin amyloid cardiomyopathy (ATTR‐CM) treated with tafamidis (VYNDAQEL®) in Japan using the Japanese Medical Data Vision (MDV) database. Methods and results: This study was a non‐interventional, retrospective cohort study of adult (≥18 years old) patients in the Japanese MDV claims database diagnosed with ATTR‐CM and with at least two tafamidis prescriptions of dose strength 4 × 20 mg/day between 1 March 2019 and 31 August 2021. The date of the first prescription was defined as the index date, with follow‐up time defined as the time between the first and last prescription plus the days' supply from the last refill. Baseline characteristics were assessed during a 12 month pre‐index period. Adherence was measured using two metrics: (i) the modified medication possession ratio (mMPR), calculated by taking the sum of days supplied for all fills within the follow‐up period, divided by the number of days of follow‐up, and reported as a percentage, with patients classified as adherent with an mMPR of ≥80%, and (ii) the proportion of days covered (PDC), calculated by taking the total number of days' supply dispensed during the follow‐up period divided by the number of days of follow‐up, adjusting for any days' supply overlap. A total of 210 patients were identified; the mean (standard deviation) age of the cohort was 77 (5.9) years, and the majority (89%) were male. The most common baseline cardiovascular comorbidities were heart failure (85%), ischaemic heart disease (66%), hypertensive diseases (49%), and diabetes (35%); 75% of patients received heart failure medications in the 12 months prior to index, with the most common being beta‐blockers (49%), diuretics (48%), angiotensin receptor blockers (30%), angiotensin‐converting enzyme inhibitors (22%), and sodium–glucose cotransporter‐2 inhibitors (8.1%). Over an average 14 month follow‐up, mean mMPR was 96% with a median of 100% [inter‐quartile range (IQR): 97–101%]; 93% of patients were adherent (defined as an mMPR ≥ 80%). In the same follow‐up period, mean PDC was 93.6% with a median of 99% (IQR: 93–100%). Persistence was high with 78% of patients having a 0 day gap between prescription refills. Conclusions: This study found high adherence rates to tafamidis in this real‐world Japanese patient population. Adherence rates in this study were similar to those reported by the tafamidis clinical trial and a previously published US commercial claims adherence analysis. Further studies should be conducted to assess the impact of real‐world adherence on real‐world outcomes. [ABSTRACT FROM AUTHOR] more...
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- 2024
- Full Text
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11. Safety assessment of Tafamidis: a real-world pharmacovigilance study of FDA adverse event reporting system (FAERS) events.
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Li, Yidan, Sun, Shengzhu, Wu, Hongyun, Zhao, Leiyong, and Peng, Wei
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ESSENTIAL hypertension ,DATABASES ,DATA mining ,ODDS ratio ,PATIENT monitoring - Abstract
Objective: Tafamidis-associated adverse events (AEs) were investigated retrospectively by data mining the US Food and Drug Administration Adverse Event Reporting System (FAERS) to inform clinical safety. Methods: Data were gathered from the FAERS database, which spans the second quarter of 2019 to the fourth quarter of 2023. A total number of 8532 reports of Tafamidis-related adverse events were detected after evaluating 8,432,351 data. Disproportionality analyses were used to quantify the signal and assess the significance of Tafamidis-associated AEs using four algorithms, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the multi-item gamma Poisson shrinker (MGPS) and the Bayesian confidence propagation neural network (BCPNN). Results: Among the 8532 reports of AEs with Tafamidis as the primary suspected drug, Tafamidis-induced AEs were identified as occurring in 27 system organ classes (SOC). A total of 207 Tafamidis-induced AEs were detected which simultaneously complied with the four algorithms. Our analysis also identified new adverse reactions including Hypoacusis, Deafness, and Essential hypertension. The median onset of adverse reactions associated with Tafamidis was 180 days (interquartile range [IQR] 51–419 days). Conclusion: Tafamidis is a drug that has shown favorable safety and tolerability results in clinical trials. However, a number of adverse reactions associated with Tafamidis have been identified through analysis of the FAERS database. In clinical applications, it is recommended to closely monitor patients' hearing while using Tafamidis. In addition, it is hoped that further experimental and clinical studies will be conducted in the future to understand the mechanism of occurrence between Tafamidis and adverse reactions such as primary hypertension, hyperlipidemia, and height reduction. [ABSTRACT FROM AUTHOR] more...
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- 2024
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12. Baseline Predictors of Adverse Outcomes for Transthyretin Amyloidosis Cardiomyopathy Patients Treated and Untreated with Tafamidis: A Canadian Referral Center Experience.
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Shahi, Karan, Miller, Robert J. H., Dykstra, Steven, Feng, Yuanchao, Howlett, Jonathan G., Jimenez-Zepeda, Victor, Veenhuyzen, Jan, White, James A., and Fine, Nowell M.
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SYSTOLIC blood pressure , *KIDNEY physiology , *TRANSTHYRETIN , *MORTALITY , *COMPETING risks , *CARDIAC amyloidosis - Abstract
Background: Tafamidis is a costly therapy that improves outcomes for patients with transthyretin amyloidosis cardiomyopathy (ATTR-CM), although significant knowledge gaps exist for predicting longer-term response to treatment. The purpose of this study was to examine baseline predictors of adverse outcomes and their association with tafamidis treatment in comparison with those untreated in a clinical cohort from a Canadian ATTR-CM referral center. Methods: Patients with a confirmed diagnosis of ATTR-CM were included. Multivariable modeling was used to identify baseline variables associated with the primary outcome of all-cause mortality and secondary outcomes of cardiovascular mortality or hospitalization. Cox proportional hazard and competing risk analyses were used, with tafamidis modeled as a time-varying covariate. Results: In total, 139 ATTR-CM patients were included, with a median age of 80.9 years [74.3–86.6 years], from 2011 to 2022. The mean follow-up was 2.9 ± 1.8 years. Eighty (55%) patients were treated with tafamidis. All-cause mortality and cardiovascular mortality alone were associated with the following baseline variables: age, clinical frailty scale, systolic blood pressure, renal function, and right ventricular size and function (all p < 0.05), with no identified interactions with tafamidis treatment. Only baseline renal function was associated with cardiovascular hospitalization (p < 0.05). Conclusion: Important baseline variables associated with adverse ATTR-CM disease outcomes included renal function, systolic blood pressure, frailty, and right ventricular size and function. The risk factors were independent of treatment with tafamidis. These findings may help improve risk stratification for determining eligibility for ATTR-CM therapies. [ABSTRACT FROM AUTHOR] more...
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- 2024
- Full Text
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13. Effect of Timely Availability of TTR-Stabilizing Therapy on Diagnosis, Therapy, and Clinical Outcomes in ATTR-CM.
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Dobner, Stephan, Zarro, Sara, Wieser, Fabian, Kassar, Mohammad, Alaour, Bashir, Wiedemann, Sebastian, Bakula, Adam, Caobelli, Federico, Stortecky, Stefan, Gräni, Christoph, Hunziker, Lukas, and Bernhard, Benedikt more...
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CARDIAC amyloidosis , *REGULATORY approval , *TRANSTHYRETIN , *MORTALITY , *DISEASE progression , *HEART failure - Abstract
Highlights: What is known? Tafamidis, a transthyretin stabilizer, reduces cardiovascular morbidity and mortality in patients with transthyretin amyloid cardiomyopathy (ATTR-CM). What is new? Availability of tafamidis increases diagnostic efficacy reducing time-to-diagnosis and time-to-therapy initiation. Timely diagnosis and availability of therapy allow therapy initiation and optimization of supportive therapies at earlier disease stages and translate into improved clinical outcomes by reducing heart failure hospitalizations and all-cause mortality. What is next? Future studies are needed to examine whether faster initiation of TTR-targeting therapies improves long-term morbidity and mortality and to identify which patients benefit most from early therapy. Background: Tafamidis reduces cardiovascular morbidity and mortality in transthyretin amyloid cardiomyopathy (ATTR-CM), yet availability and access to therapy vary. Objective: To determine how availability and access to tafamidis impact time-to-diagnosis, time-to-therapy, and cardiovascular outcomes in ATTR-CM. Methods: Ninety-one consecutive ATTR-CM (~97% wt-TTR) patients diagnosed between June 2019 and June 2021 were evaluated for tafamidis. Access to therapy was regulated by compassionate use [n(CU) = 42] prior to, and insurance [n(IA) = 49] after regulatory approval. Results: Tafamidis was started in 37/42 (88.1%), and 39/49 (79.6%) patients, respectively. At diagnosis, ATTR-CM disease stage (≤stage 2: 88.2% vs. 90.9%, p = 0.92) was similar between groups. Timely access (after tafamidis approval) reduced the median time from first presentation to diagnosis from 6.2 (IQR: 1.3–28.9) to 2.4 (0.7–21.7) months, and from first presentation to therapy from 24.4 (10.7–46.8) to 11.8 (6.4–32.4) months. While RV function significantly worsened between diagnosis and therapy initiation in CU patients diagnosed before tafamidis approval (S'-velocity 10.0 ± 2.2 to 9.2 ± 2.2 cm/s; p = 0.018; TAPSE 17.3 ± 4.7 to 15.7 ± 3.9 mm, p = 0.008), it remained unchanged in IA patients (S'-velocity 9.6 ± 2.6 to 9.4 ± 2.3 cm/s; p = 0.83; TAPSE 15.6 ± 4.2 to 16.3 ± 3.1 mm, p = 0.45). After a median follow-up of 42.3 and 24.9 months in CU and IA patients, respectively, timely availability was associated with a reduction in annual heart failure hospitalizations (0.40 vs. 0.16 per patient, p < 0.001) and improved MACE-free survival (HR = 0.51; 95%CI: 0.26–1.00; p = 0.051). Timely diagnosis (<12-months) prolonged MACE-free survival (HR = 0.424; 95%CI: 0.22–0.81; p = 0.004), and reduced HFH (HR = 0.40; 95%CI: 0.19–0.81); p = 0.011) and all-cause mortality (HR = 0.29; 95%CI: 0.11–0.74); p = 0.009). Conclusions: Availability of tafamidis improves diagnostic efficacy in ATTR-CM patients. Timely diagnosis and initiation of therapy reduces adverse cardiovascular events. [ABSTRACT FROM AUTHOR] more...
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- 2024
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14. Effect of tafamidis on left atrial function of patients with transthyretin amyloid cardiomyopathy.
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Uemura, Koya, Ichikawa, Yasushi, Nagai, Shun, Nishihara, Yu, Todo, Saki, Oota, Eri, Odajima, Susumu, Takeuchi, Kimikazu, Kintsu, Masayuki, Fukuda, Terunobu, Hisamatsu, Eriko, Hirata, Ken-ichi, and Tanaka, Hidekazu more...
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GLOBAL longitudinal strain , *LEFT heart atrium , *LOGISTIC regression analysis , *AMYLOID ,CARDIOVASCULAR disease related mortality - Abstract
Transthyretin amyloid cardiomyopathy (ATTR-CM) is characterized by the functional and structural effects of amyloid infiltration, predominantly within the ventricles, causing biventricular wall thickening. Amyloid infiltration can be observed in the left atrium in ATTR-CM patients, but the association of left atrial (LA) myocardial function with cardiovascular events and of changes in LA myocardial function with tafamidis administration have not yet been clarified. Our aim was, therefore, to use speckle-tracking strain for investigating LA myocardial function in patients with ATTR-CM treated with tafamidis. We studied 55 patients with biopsy-proven ATTR-CM who had been treated with tafamidis (age: 76 ± 2 years, male: 93%). For speckle-tracking analysis of LA myocardial function, the systolic LA strain (LA reservoir function) was defined for this study as LA myocardial function from the apical 4-chamber view. The primary endpoint was defined as a composite comprising cardiovascular death and/or heart failure hospitalization after tafamidis administration over a median follow-up period of 28 ± 4 months. Patients with baseline LA strain < 8.6% (median value) experienced significantly more cardiovascular events than those without (log-rank P = 0.002). Moreover, LA strain in 26 patients worsened after tafamidis administration, and multivariate logistic regression analysis showed age, global longitudinal strain and relative apical longitudinal strain index were identified as independent determinants of deterioration of LA strain after tafamidis administration. In conclusion, baseline LA reservoir function is closely associated with cardiovascular events after tafamidis administration, and could be an additional parameter for the management of patients with ATTR-CM. [ABSTRACT FROM AUTHOR] more...
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- 2024
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15. Effectiveness of patisiran after switching from tafamidis for the treatment of hereditary transthyretin‐mediated amyloidosis with polyneuropathy.
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Labeyrie, Celine, Merkel, Madeline, Sethi, Sakshi, Popadic, Lyuba, Yang, Hongbo, Sweetser, Marianne T., Lin, Hollis, and Adams, David
- Abstract
Background and purpose: Hereditary transthyretin‐mediated amyloidosis with polyneuropathy (ATTRv‐PN [v for variant]) is a rare, progressive disease associated with multisystemic impairments. This study assessed the real‐world outcomes of patients with ATTRv‐PN who switched from tafamidis to patisiran, as well as the reasons for the treatment switch. Methods: This was a retrospective chart review study at a large expert referral center. Data were extracted from medical charts of patients with ATTRv‐PN who switched from tafamidis to patisiran on or before 30 August 2019. Data elements included demographic and clinical characteristics, rationale for switch, and disease measures evaluated from tafamidis initiation through the 12‐month patisiran treatment period. Results: Among the 24 patients with ATTRv‐PN included in the study, 50.0% had a V30M variant, and the mean (SD) age was 67.3 (8.0) years. During tafamidis treatment (mean [SD] = 30.1 [17.5] months) before switching to patisiran, patients worsened across multiple polyneuropathy measures, including walking ability, Neuropathy Impairment Score, and autonomic function. Neuropathic disease progression on tafamidis was the principal reason for switching to patisiran. After 12 months on patisiran (mean [SD] = 11.7 [1.4] months), patients experienced attenuated disease progression or improvement in the aforementioned measures of polyneuropathy. Conclusions: Switching from tafamidis to patisiran attenuated the rate of functional decline, and most patients experienced stabilization or improvement of at least one polyneuropathy measure within 12 months of patisiran treatment. Timely switch from tafamidis to patisiran can be beneficial to avoid rapid disease progression in patients with ATTRv‐PN. [ABSTRACT FROM AUTHOR] more...
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- 2024
- Full Text
- View/download PDF
16. Response to therapy with tafamidis 61 mg in patients with cardiac transthyretin amyloidosis: real-world experience since approval.
- Author
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aus dem Siepen, Fabian, Meissner, Christopher, Hofmann, Eva, Hein, Selina, Nagel, Christian, Hegenbart, Ute, Schönland, Stefan O., Andre, Florian, Frey, Norbert, and Kristen, Arnt V.
- Subjects
- *
BRAIN natriuretic factor , *SURVIVAL rate , *KARNOFSKY Performance Status , *VENTRICULAR ejection fraction , *GLOMERULAR filtration rate , *CARDIAC amyloidosis , *HEART failure - Abstract
Aims: Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive disease that causes heart failure due to amyloid fibril deposition. Tafamidis was approved as the first causal treatment in 2020. We here report on real-world data in patients treated with tafamidis for at least 12 months according to the recently defined European Society for Cardiology (ESC) consensus criteria for disease progression. Methods and results: Three hundred and eight wildtype and 31 hereditary ATTR-CM patients were prospectively enrolled after first diagnosis of ATTR-CM and initiation of tafamidis 61 mg once daily treatment. After 12 months, significant deterioration in Karnofsky Index, estimated glomerular filtration rate (eGFR), N-terminal brain natriuretic peptide (NT-proBNP), septum thickness and left ventricular ejection fraction (LVEF) could be observed, significant disease progression was only detected in 25 patients (9%) using ESC consensus criteria. Mean survival time was 37 months with no differences between responders and non-responders. NT-proBNP was the only independent predictor for poor therapy response (p =.008). Conclusions: The majority of patients showed no significant disease progression according to the ESC consensus criteria after 12 months of therapy with tafamidis. However, at 12 months, treatment response based on the ESC consensus criteria was not associated with improved survival. Moreover, higher levels of NT-proBNP at diagnosis of ATTR-CM appears to predict poorer treatment response, confirming that timely initiation of therapy is advantageous. [ABSTRACT FROM AUTHOR] more...
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- 2024
- Full Text
- View/download PDF
17. Safety, Tolerability, and Outcomes of Tafamidis for the Treatment of Acquired Amyloid Neuropathy in Domino Liver Transplant Recipients.
- Author
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Nedkova-Hristova, Velina, Donadeu, Laura, Baliellas, Carmen, González-Costello, José, Lladó, Laura, González-Vilatarsana, Emma, Vélez-Santamaría, Valentina, de la Prida, Miosés Morales, Bestard, Oriol, and Casasnovas, Carlos more...
- Subjects
- *
LIVER transplantation , *AMYLOID , *NEUROPATHY , *AUDITORY neuropathy , *GRAFT rejection , *IATROGENIC diseases , *CEREBRAL amyloid angiopathy - Abstract
Introduction: Acquired amyloid neuropathy is an iatrogenic disease that appears years after a domino liver transplant. The objectives of our study are to analyze the efficacy and tolerability of tafamidis for the treatment of acquired amyloid neuropathy in domino liver transplant recipients. This post-authorization, prospective, longitudinal study included seven domino liver transplant recipients with acquired amyloid neuropathy who received treatment with tafamidis for 18 months. Methods: The primary endpoints were the response rate, defined as those patients with an increase of < 2 points on the Neurological Impairment Score (NIS) from baseline, and the change in the NIS score from baseline. Secondary endpoints included the Quantitative Sensory Test, 10-m walk test, quality of life (Norfolk), and disability (Rasch-built Overall Disability Scale). As safety parameters, the evidence of graft rejection, changes in immunosuppressive trough levels and changes in antiviral and allogeneic cellular immunity before and 12 months after tafamidis treatment were also assessed. Results: Six patients (85.7%) had responded at 18-months. Compared to baseline, we observed non-statistically significant improvement in mean NIS score at 6 months (− 2.54 points, CI − 5.92 to 0.84), 12 months (− 3.25 points; CI − 6.63 to 0.13), and 18 months (− 2.35 points; CI − 5.74 to 1.02). Changes in the Quantitative Sensory Test, 10-m walk tests and the quality of life and disability questionnaires were not statistically significant. The use of tafamidis did not induce relevant side effects or drug interactions. Also, no acute rejections events nor changes in functional adaptive immunity were observed. Conclusion: Our study supports the safety and tolerability of tafamidis for the treatment of acquired amyloid neuropathy in domino liver transplant recipients. Tafamidis shows promise as a useful treatment in the clinical management of these patients. Future randomized placebo-controlled clinical trials with longer follow-up durations are needed. [ABSTRACT FROM AUTHOR] more...
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- 2024
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18. Current Therapies and Future Horizons in Cardiac Amyloidosis Treatment.
- Author
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Vogel, Julia, Carpinteiro, Alexander, Luedike, Peter, Buehning, Florian, Wernhart, Simon, Rassaf, Tienush, and Michel, Lars
- Abstract
Purpose of Review: Cardiac amyloidosis (CA) is a condition characterized by misfolding and extracellular deposition of proteins, leading to organ dysfunction. While numerous forms of CA exist, two subtypes dominate clinical prevalence: Transthyretin amyloid (ATTR) and immunoglobulin light chain amyloid. Recent Findings: The current scientific landscape reflects the urgency to advance therapeutic interventions with over 100 ongoing clinical trials. Heart failure treatment is affected by CA phenotype with poor tolerance of otherwise frequently used medications. Treating comorbidities including atrial fibrillation and valvular disease remains a challenge in CA, driven by technical difficulties and uncertain outcomes. Tafamidis is the first ATTR-stabilizer approved with a rapidly growing rate of clinical use. In parallel, various new therapeutic classes are in late-stage clinical trials including silencers, antibodies and genetic therapy. Summary: Managing CA is a critical challenge for future heart failure care. This review delineates the current standard-of-care and scientific landscape of CA therapy. [ABSTRACT FROM AUTHOR] more...
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- 2024
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19. Monitoring the Efficacy of Tafamidis in ATTR Cardiac Amyloidosis by MRI-ECV: A Systematic Review and Meta-Analysis.
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Kato, Shingo, Azuma, Mai, Horita, Nobuyuki, and Utsunomiya, Daisuke
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CARDIAC magnetic resonance imaging ,MAGNETIC resonance imaging ,CARDIAC amyloidosis ,TREATMENT effectiveness ,HETEROGENEITY - Abstract
Background: The usefulness of monitoring treatment effect of tafamidis using magnetic resonance imaging (MRI) extracellular volume fraction (ECV) has been reported. Objective: we conducted a meta-analysis to evaluate the usefulness of this method. Methods: Data from 246 ATTR-CMs from six studies were extracted and included in the analysis. An inverse variance meta-analysis using a random effects model was performed to evaluate the change in MRI-ECV before and after tafamidis treatment. The analysis was also performed by classifying the patients into ATTR-CM types (wild-type or hereditary). Results: ECV change before and after tafamidis treatment was 0.33% (95% CI: −1.83–2.49, I
2 = 0%, p = 0.76 for heterogeneity) in the treatment group and 4.23% (95% CI: 0.44–8.02, I2 = 0%, p = 0.18 for heterogeneity) in the non-treatment group. The change in ECV before and after treatment was not significant in the treated group (p = 0.76), but there was a significant increase in the non-treated group (p = 0.03). There was no difference in the change in ECV between wild-type (95% CI: −2.65–3.40) and hereditary-type (95% CI: −9.28–4.28) (p = 0.45). Conclusions: The results of this meta-analysis suggest that MRI-ECV measurement is a useful imaging method for noninvasively evaluating the efficacy of tafamidis treatment for ATTR-CM. [ABSTRACT FROM AUTHOR] more...- Published
- 2024
- Full Text
- View/download PDF
20. Myocardial work assessment to improve baseline risk stratification in patients with transthyretin amyloidosis
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Ana Moya, Elayne Kelen de Oliveira, Monika Beles, Dimitri Buytaert, Marc Goethals, Riet Dierckx, Jeroen Dauw, Jozef Bartunek, Ward A. Heggermont, and Marc Vanderheyden
- Subjects
Myocardial Work ,Cardiac Transthyretin amyloidosis ,Tafamidis ,Non-invasive imaging ,Strain ,NT-proBNP ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background: Cardiac transthyretin (ATTR) amyloidosis is an often underdiagnosed and potentially fatal disorder associated with poor survival. The National Amyloidosis Centre (NAC) staging system, based on NT-proBNP level and eGFR value, discriminates patients according to survival rates. However, NAC stage II involves a heterogenous group of patients with variable prognosis. This retrospective single-center study was set up to explore the potential role of myocardial work (MW) analysis to enhance risk stratification of ATTR patients prior to therapy. Methods and Results: 37 patients diagnosed with ATTR between March 2021 and August 2023 were included. Baseline NT-proBNP and eGFR values were collected and LVEF, GLS and MW parameters were obtained from stored echocardiographic images. Patients were categorized per NAC stage (16 NAC I, 13 NAC II and 8 NAC III). Whereas the survival rate in NAC II and NAC III was significantly worse than in NAC I (p = 0.031 and p = 0.045 respectively), no significant difference was found between NAC II and III. In the ROC analysis, GCW proved to be the best survival predictor (AUC: 0.7) with optimal cut-off value 1294 mmHg%. Patients from NAC stage II were re-stratified according to GCW cut-off into HIGH RISK together with patients from NAC III or LOW RISK together with patients from NAC I. Patients in the HIGH RISK group exhibited a significantly worse prognosis with only 40 % survival at 2 years follow-up. Conclusion: Our results demonstrate the advantages of incorporating MW analysis, particularly the use of a GCW cut-off, in the baseline risk stratification of ATTR patients. more...
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- 2024
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21. No body fits in the test tube – the case of transthyretin.
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Ulaszek, Seweryn, Wiśniowska, Barbara, and Lisowski, Bartek
- Subjects
- *
REVERSIBLE phase transitions , *HEPATOCYTE nuclear factors , *SURFACE plasmon resonance , *CONSERVATION of mass , *CARRIER proteins - Abstract
The document discusses the dynamics of transthyretin (TTR) tetramer stabilization in clinical studies using drugs like tafamidis and acoramidis. It explores the dissociation of TTR tetramers into monomers and their re-association, both in vitro and in vivo, shedding light on the impact of tetramer stabilizers on TTR concentration in blood plasma. The model proposed in the document suggests that the increase in serum TTR levels observed in response to stabilizers is not solely due to the drugs' stabilizing effect but also involves changes in TTR production and elimination rates. The study aims to enhance understanding of transthyretin-related pathologies and amyloidoses, emphasizing the importance of considering multiple factors beyond tetramer stabilization in pharmacotherapy. [Extracted from the article] more...
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- 2024
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22. Impact of Tafamidis on [99mTc]Tc-pyrophosphate Scintigraphy in Ala97Ser Hereditary Transthyretin amyloid cardiomyopathy: significant initial reduction with stable Long-Term effects
- Author
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Yu, An-Li, Chen, Yi-Chieh, Tsai, Cheng-Hsuan, Chao, Chi-Chao, Su, Mao-Yuan, Shun, Chia-Tung, Hsueh, Hsueh-Wen, Juang, Jyh-Ming Jimmy, Lee, Ming-Jen, Tseng, Ping-Huei, Hsieh, Sung-Tsang, Cheng, Mei-Fang, and Lin, Yen-Hung more...
- Published
- 2025
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- View/download PDF
23. Recovery of right ventricular function in patients with transthyretin cardiac amyloidosis after one-year tafamidis administration
- Author
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Nagai, Tomoo, Horinouchi, Hitomi, Hashimoto, Kaho, Ijichi, Takeshi, Yoshioka, Koichiro, and Ikari, Yuji
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- 2024
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24. Tafamidis therapy in transthyretin amyloid cardiomyopathy: a narrative review from clinical trials and real-world evidence
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Ikponmwosa Jude Ogieuhi, Oshomoh Mark-Anthony Ugiomoh, Kudzaishe Muzofa, Kristen Callender, Johnson David Ayodeji, Nnokam Prayer Nnekachi, Barkavi Thiyagarajan, Emmanuel Obokhai Uduigwome, Abhay Kapoor, Moses Chukwuebuka Odoeke, Reem Gamaleldin Hassan Mohamed, and Courage Idahor more...
- Subjects
Amyloidosis ,Cardiomyopathy ,ATTR-CM ,Tafamidis ,Therapeutic intervention ,Heart failure ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Abstract Background Amyloidosis is a heterogeneous group of disorders caused by the extracellular deposition of insoluble misfolded proteins, leading to end-organ damage. Transthyretin amyloid cardiomyopathy (ATTR-CM) is a subtype in which a protein known as transthyretin accumulates within the heart tissue, progressively resulting in restrictive cardiomyopathy and heart failure. Due to the progressive nature of ATTR-CM, clinical management requires efficacious regimens to manage the debilitating condition and Tafamidis shows promising results in this regard. Main body ATTR-CM poses a significant challenge due to its nature and limited therapeutic options. Tafamidis is a novel therapy designed to stabilize the transthyretin tetramers, inhibiting the formation of amyloid fibrils. It has emerged as a promising treatment and the only FDA-approved drug for ATTR-CM. Tafamidis' role in slowing disease progression and improving outcomes in patients with ATTR-CM has been demonstrated in the major randomized control trial ATTR-ACT with promising open-label extension studies, some still ongoing. Additionally, real-world evidence supports its use in clinical practice, showing its role in reducing morbidity and mortality associated with this condition. Clinical evidence shows its efficacy in improving symptoms and cardiac function in patients. Case studies also reveal significant benefits to patients like reducing myocardial damage, reversal of atrial fibrillation, and resolution of heart failure symptoms. Real-world outcomes and clinical trials show a consistent reduction in amyloid deposition, cardiovascular-related hospitalizations, and all-cause mortality with Tafamidis therapy. Conclusion Tafamidis is an essential component of the treatment of ATTR-CM and this narrative review synthesizes the current evidence regarding safety, efficacy, and utilization in real practice. While it shows promising effects, its effectiveness may also vary and high cost precludes real-world large-scale studies. Overall, Tafamidis emerges as a valuable therapeutic option for managing ATTR-CM. more...
- Published
- 2024
- Full Text
- View/download PDF
25. Analysis of post-market adverse events of tafamidis base on the FDA adverse event reporting system
- Author
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Fan Wu, He Zhu, and Yue Zhang
- Subjects
Tafamidis ,Amyloid cardiomyopathy ,Adverse event ,Real-world data-mining ,Pharmacovigilance ,Medicine ,Science - Abstract
Abstract Tafamidis is the world's first and only oral drug approved to treat the rare disease transthyretin amyloid cardiomyopathy (ATTR-CM). Medicines are known to have different adverse reactions during the course of treatment. However, the current limited clinical studies did not identify significant adverse drug reactions to tafamidis. Tafamidis has been on the market for 5 years now, a large number of adverse drug event (ADE) reports with tafamidis as the primary suspected drug have been reported in the United Food and Drug Administration's adverse event reporting system (FAERS). We retrieved 8170 adverse event reports in FAERS with tafamidis as the first suspected drug, and mined these reports for positive signals to perform risk warnings for potentially possible adverse events with tafamidis. We found that a large number of adverse events associated with the primary disease were reported due to insufficient awareness of ATTR among the reporters, leading to a large number of positive signals reported in the cardiac disorders system. We also found that tafamidis has the potential to cause an adverse event risks of ear and labyrinth disorders system and urinary tract infection bacterial, which deserve continued clinical attention. more...
- Published
- 2024
- Full Text
- View/download PDF
26. Treatment characteristics of patients with hereditary transthyretin amyloidosis: a cohort study
- Author
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Taha N. Qarni, Felipe J. S. Jones, Brian Drachman, Sami Khella, Janice Pieretti, Nicolas Sarmiento Bustamante, and Chafic Karam
- Subjects
Transthyretin amyloidosis ,Tafamidis ,Inotersen ,Diflunisal ,Patisiran ,Vutrisiran ,Medicine - Abstract
Abstract Background There are novel medications approved for the treatment of hereditary transthyretin amyloidosis (ATTRv), classified as transthyretin (TTR) stabilizers or gene silencers. While many patients may be on both classes of medications, there is no data available on the safety and efficacy of combination therapy. Objectives To describe ATTRv patient and TTR-targeted therapy characteristics in a US cohort, and compare outcomes with combination therapy versus monotherapy. Methods We performed a retrospective cohort study with electronic health record data of patients with ATTRv seen at a single institution between January 2018 and December 2022. We collected data on symptomatology, gene mutation, disease severity, ATTRv treatment, hospitalizations, and mortality. Results One hundred sixty-two patients with ATTRv were identified. The average age at diagnosis was 65 years. 86 patients (53%) had the V122I variant. 119 patients were symptomatic, of whom 103 were started on ATTRv-specific treatment. 41 patients (40%) had cardiomyopathy only, and 53 (51%) had a mixed phenotype of cardiomyopathy and neuropathy. 38 patients (37%) received therapy with both a gene silencer and protein stabilizer. 9 patients (15%) in the monotherapy group had two or more cardiac hospitalizations after starting treatment, compared to 3 patients (9%) on combination therapy (p=0.26). The adjusted hazard ratio of all-cause mortality for the patients on combination therapy compared to monotherapy was 0.37 (0.08-1.8, p=0.21). Conclusions While the efficacy is unproven, over one-third of patients with ATTRv are on both a stabilizer and a silencer. There were no safety issues for combination therapy. There was a trend towards improved hospitalizations and survival in patients in the combination group but this was not statistically significant. Larger studies with longer follow-up are necessary to determine benefit of combination therapy. more...
- Published
- 2024
- Full Text
- View/download PDF
27. Safety, Tolerability, and Outcomes of Tafamidis for the Treatment of Acquired Amyloid Neuropathy in Domino Liver Transplant Recipients
- Author
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Velina Nedkova-Hristova, Laura Donadeu, Carmen Baliellas, José González-Costello, Laura Lladó, Emma González-Vilatarsana, Valentina Vélez-Santamaría, Miosés Morales de la Prida, Oriol Bestard, and Carlos Casasnovas more...
- Subjects
Tafamidis ,Transthyretin ,Amyloidosis ,Domino liver transplant ,Neuropathy ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract Introduction Acquired amyloid neuropathy is an iatrogenic disease that appears years after a domino liver transplant. The objectives of our study are to analyze the efficacy and tolerability of tafamidis for the treatment of acquired amyloid neuropathy in domino liver transplant recipients. This post-authorization, prospective, longitudinal study included seven domino liver transplant recipients with acquired amyloid neuropathy who received treatment with tafamidis for 18 months. Methods The primary endpoints were the response rate, defined as those patients with an increase of more...
- Published
- 2024
- Full Text
- View/download PDF
28. Tafamidis therapy in transthyretin amyloid cardiomyopathy: a narrative review from clinical trials and real-world evidence.
- Author
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Ogieuhi, Ikponmwosa Jude, Ugiomoh, Oshomoh Mark-Anthony, Muzofa, Kudzaishe, Callender, Kristen, Ayodeji, Johnson David, Nnekachi, Nnokam Prayer, Thiyagarajan, Barkavi, Uduigwome, Emmanuel Obokhai, Kapoor, Abhay, Odoeke, Moses Chukwuebuka, Mohamed, Reem Gamaleldin Hassan, and Idahor, Courage more...
- Abstract
Background: Amyloidosis is a heterogeneous group of disorders caused by the extracellular deposition of insoluble misfolded proteins, leading to end-organ damage. Transthyretin amyloid cardiomyopathy (ATTR-CM) is a subtype in which a protein known as transthyretin accumulates within the heart tissue, progressively resulting in restrictive cardiomyopathy and heart failure. Due to the progressive nature of ATTR-CM, clinical management requires efficacious regimens to manage the debilitating condition and Tafamidis shows promising results in this regard. Main body: ATTR-CM poses a significant challenge due to its nature and limited therapeutic options. Tafamidis is a novel therapy designed to stabilize the transthyretin tetramers, inhibiting the formation of amyloid fibrils. It has emerged as a promising treatment and the only FDA-approved drug for ATTR-CM. Tafamidis' role in slowing disease progression and improving outcomes in patients with ATTR-CM has been demonstrated in the major randomized control trial ATTR-ACT with promising open-label extension studies, some still ongoing. Additionally, real-world evidence supports its use in clinical practice, showing its role in reducing morbidity and mortality associated with this condition. Clinical evidence shows its efficacy in improving symptoms and cardiac function in patients. Case studies also reveal significant benefits to patients like reducing myocardial damage, reversal of atrial fibrillation, and resolution of heart failure symptoms. Real-world outcomes and clinical trials show a consistent reduction in amyloid deposition, cardiovascular-related hospitalizations, and all-cause mortality with Tafamidis therapy. Conclusion: Tafamidis is an essential component of the treatment of ATTR-CM and this narrative review synthesizes the current evidence regarding safety, efficacy, and utilization in real practice. While it shows promising effects, its effectiveness may also vary and high cost precludes real-world large-scale studies. Overall, Tafamidis emerges as a valuable therapeutic option for managing ATTR-CM. [ABSTRACT FROM AUTHOR] more...
- Published
- 2024
- Full Text
- View/download PDF
29. Analysis of post-market adverse events of tafamidis base on the FDA adverse event reporting system.
- Author
-
Wu, Fan, Zhu, He, and Zhang, Yue
- Abstract
Tafamidis is the world's first and only oral drug approved to treat the rare disease transthyretin amyloid cardiomyopathy (ATTR-CM). Medicines are known to have different adverse reactions during the course of treatment. However, the current limited clinical studies did not identify significant adverse drug reactions to tafamidis. Tafamidis has been on the market for 5 years now, a large number of adverse drug event (ADE) reports with tafamidis as the primary suspected drug have been reported in the United Food and Drug Administration's adverse event reporting system (FAERS). We retrieved 8170 adverse event reports in FAERS with tafamidis as the first suspected drug, and mined these reports for positive signals to perform risk warnings for potentially possible adverse events with tafamidis. We found that a large number of adverse events associated with the primary disease were reported due to insufficient awareness of ATTR among the reporters, leading to a large number of positive signals reported in the cardiac disorders system. We also found that tafamidis has the potential to cause an adverse event risks of ear and labyrinth disorders system and urinary tract infection bacterial, which deserve continued clinical attention. [ABSTRACT FROM AUTHOR] more...
- Published
- 2024
- Full Text
- View/download PDF
30. Tafamidis 61 mg Patient Characteristics and Persistency? A Retrospective Analysis of German Statutory Health Insurance Data (IQVIA™ LRx).
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Attal, Sepideh, Kemner, Jason, Alvir, Jose, Barth, Sebastian, and Schuessler, Sofia
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- *
HEALTH insurance , *PATIENT compliance , *PHARMACY databases , *RETROSPECTIVE studies , *DATABASES - Abstract
Introduction: Tafamidis is the first drug approved by the European Commission for the treatment of wild-type or hereditary transthyretin amyloid cardiomyopathy (ATTR-CM) in adults to reduce cardiovascular mortality and cardiovascular-related hospitalization. Real-world treatment patterns of tafamidis 61 mg in Germany are not well studied in patients with ATTR-CM. Methods: This was a non-interventional, retrospective, observational cohort study of adult patients in Germany based on the IQVIA pharmacy claims database (IQVIA™ LRx). Patients included in the analysis were statutory insured and received at least one prescription of tafamidis 61 mg between March 1, 2020 and August 31, 2022. Treatment adherence was analyzed using the modified medical possession ratio (mMPR) and proportion of days covered (PDC). Results: Overall, 1565 adult patients received at least one tafamidis prescription in the study period. Their mean age was 78.3 years, 82.4% were male, and 23.2% were treated by a cardiologist. Persistency rates for patients treated with tafamidis 61 mg were high: 78.0% for 12 months and 65.1% for 24 months after treatment initiation. Patients also had high adherence rate on filling their prescriptions on time: 94.6% and 90.5% of patients had adherence rates of at least 80%, measured by mMPR and PDC, respectively. Conclusions: In the IQVIA™ LRx database, patients prescribed tafamidis 61 mg in Germany displayed high adherence and persistency rates, which suggest good drug tolerability and ease of use. [ABSTRACT FROM AUTHOR] more...
- Published
- 2024
- Full Text
- View/download PDF
31. Real-World Effectiveness of High-Dose Tafamidis on Neurologic Disease Progression in Mixed-Phenotype Variant Transthyretin Amyloid Cardiomyopathy.
- Author
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Streicher, Nicholas, Amass, Leslie, Wang, Rong, Stephens, Jennifer M., LeMasters, Traci, Raina, Rutika, Merrill, Emma, and Sheikh, Farooq H.
- Subjects
- *
NEUROLOGICAL disorders , *TRANSTHYRETIN , *DISEASE progression , *AMYLOID , *MUSCLE weakness , *CARDIAC amyloidosis , *CEREBRAL amyloid angiopathy - Abstract
Introduction: Transthyretin amyloidosis (ATTR) is a progressive, heterogeneous rare disease manifesting as ATTR polyneuropathy (ATTR-PN), ATTR cardiomyopathy (ATTR-CM), or a mixed phenotype. Tafamidis meglumine (20 mg po qd) is approved in some markets to delay neurologic progression in ATTR-PN, while high-dose tafamidis (80/61 mg po qd) is approved worldwide to reduce cardiovascular mortality and cardiovascular-related hospitalization in ATTR-CM. The objective of this study was to assess the real-world benefit of high-dose tafamidis for delaying neurologic progression in patients with mixed-phenotype variant ATTR-CM (ATTRv-CM). Methods: This exploratory, retrospective, observational cohort study evaluated anonymized electronic medical records and included adult patients with mixed-phenotype ATTRv-CM treated with high-dose tafamidis for at least 6 months. Neurologic assessments included the Medical Research Council (MRC) Scale for Muscle Strength, Neuropathy Impairment Score (NIS) muscle weakness subscale, and Polyneuropathy Disability (PND) instrument. Modified body mass index (mBMI) was also assessed. Results: Patients (N = 10) started tafamidis treatment an average of 3.8 months after diagnosis, with an average treatment duration of 20.8 months. Seven of 10 patients demonstrated normal muscle strength on the MRC scale throughout the study, and 9 of 10 patients had no decline in muscle strength during the post-treatment period. The NIS muscle weakness subscale score was ≤ 60 for all patients in the study at all time points, suggesting normal function to mild impairment. Six of 10 patients had no change in walking capacity as measured by the PND instrument at pre- and post-assessments, while one-third of patients had a decrease in PND stage (signaling improvement) from pre- to post-assessment. mBMI remained relatively stable throughout the study. Conclusion: This is the first real-world study to demonstrate the potential value of high-dose tafamidis for delaying neurologic disease progression in patients with mixed-phenotype ATTRv-CM. The findings underscore the importance of multidisciplinary assessment for patients with ATTR amyloidosis. Trial registration: ClinicalTrials.gov: NCT05139680. [ABSTRACT FROM AUTHOR] more...
- Published
- 2024
- Full Text
- View/download PDF
32. Treatment characteristics of patients with hereditary transthyretin amyloidosis: a cohort study.
- Author
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Qarni, Taha N., Jones, Felipe J. S., Drachman, Brian, Khella, Sami, Pieretti, Janice, Bustamante, Nicolas Sarmiento, and Karam, Chafic
- Subjects
- *
TRANSTHYRETIN , *ELECTRONIC health records , *AMYLOIDOSIS , *COHORT analysis , *GENE therapy - Abstract
Background: There are novel medications approved for the treatment of hereditary transthyretin amyloidosis (ATTRv), classified as transthyretin (TTR) stabilizers or gene silencers. While many patients may be on both classes of medications, there is no data available on the safety and efficacy of combination therapy. Objectives: To describe ATTRv patient and TTR-targeted therapy characteristics in a US cohort, and compare outcomes with combination therapy versus monotherapy. Methods: We performed a retrospective cohort study with electronic health record data of patients with ATTRv seen at a single institution between January 2018 and December 2022. We collected data on symptomatology, gene mutation, disease severity, ATTRv treatment, hospitalizations, and mortality. Results: One hundred sixty-two patients with ATTRv were identified. The average age at diagnosis was 65 years. 86 patients (53%) had the V122I variant. 119 patients were symptomatic, of whom 103 were started on ATTRv-specific treatment. 41 patients (40%) had cardiomyopathy only, and 53 (51%) had a mixed phenotype of cardiomyopathy and neuropathy. 38 patients (37%) received therapy with both a gene silencer and protein stabilizer. 9 patients (15%) in the monotherapy group had two or more cardiac hospitalizations after starting treatment, compared to 3 patients (9%) on combination therapy (p=0.26). The adjusted hazard ratio of all-cause mortality for the patients on combination therapy compared to monotherapy was 0.37 (0.08-1.8, p=0.21). Conclusions: While the efficacy is unproven, over one-third of patients with ATTRv are on both a stabilizer and a silencer. There were no safety issues for combination therapy. There was a trend towards improved hospitalizations and survival in patients in the combination group but this was not statistically significant. Larger studies with longer follow-up are necessary to determine benefit of combination therapy. Key summary points: • A large proportion of patients with ATTRv are on both a silencer and stabilizer despite the lack of evidence of benefit. • In our patients' population, the combination therapy was found to be safe. • No clear benefit was found between patients on monotherapy versus combination therapy. However, a trend of less hospitalization and mortality was observed in those patients on combination therapy. [ABSTRACT FROM AUTHOR] more...
- Published
- 2024
- Full Text
- View/download PDF
33. Amyloidose hereditaire a transthyretine accompagnee d'un syndrome du canal carpien
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Zaki, Nicole, Miller, Nicholas J., Frosk, Patrick, and Sharma, Aditya
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Pantoprazole ,Inotersen ,Tafamidis - Abstract
Nous avons hospitalise en medecine interne generale un homme droitier de 65 ans qui presentait une insuffisance cardiaque decompensee et des saignements gastro-intestinaux. Il avait d'abord consulte son medecin de [...] more...
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- 2024
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34. Tafamidis 61 mg Patient Characteristics and Persistency? A Retrospective Analysis of German Statutory Health Insurance Data (IQVIA™ LRx)
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Sepideh Attal, Jason Kemner, Jose Alvir, Sebastian Barth, and Sofia Schuessler
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ATTR-CM ,Adherence ,Persistence ,Tafamidis ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Abstract Introduction Tafamidis is the first drug approved by the European Commission for the treatment of wild-type or hereditary transthyretin amyloid cardiomyopathy (ATTR-CM) in adults to reduce cardiovascular mortality and cardiovascular-related hospitalization. Real-world treatment patterns of tafamidis 61 mg in Germany are not well studied in patients with ATTR-CM. Methods This was a non-interventional, retrospective, observational cohort study of adult patients in Germany based on the IQVIA pharmacy claims database (IQVIA™ LRx). Patients included in the analysis were statutory insured and received at least one prescription of tafamidis 61 mg between March 1, 2020 and August 31, 2022. Treatment adherence was analyzed using the modified medical possession ratio (mMPR) and proportion of days covered (PDC). Results Overall, 1565 adult patients received at least one tafamidis prescription in the study period. Their mean age was 78.3 years, 82.4% were male, and 23.2% were treated by a cardiologist. Persistency rates for patients treated with tafamidis 61 mg were high: 78.0% for 12 months and 65.1% for 24 months after treatment initiation. Patients also had high adherence rate on filling their prescriptions on time: 94.6% and 90.5% of patients had adherence rates of at least 80%, measured by mMPR and PDC, respectively. Conclusions In the IQVIA™ LRx database, patients prescribed tafamidis 61 mg in Germany displayed high adherence and persistency rates, which suggest good drug tolerability and ease of use. more...
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- 2024
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35. Real-World Effectiveness of High-Dose Tafamidis on Neurologic Disease Progression in Mixed-Phenotype Variant Transthyretin Amyloid Cardiomyopathy
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Nicholas Streicher, Leslie Amass, Rong Wang, Jennifer M. Stephens, Traci LeMasters, Rutika Raina, Emma Merrill, and Farooq H. Sheikh
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ATTR amyloidosis ,ATTR cardiomyopathy ,ATTR polyneuropathy ,Real-world ,Tafamidis ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Abstract Introduction Transthyretin amyloidosis (ATTR) is a progressive, heterogeneous rare disease manifesting as ATTR polyneuropathy (ATTR-PN), ATTR cardiomyopathy (ATTR-CM), or a mixed phenotype. Tafamidis meglumine (20 mg po qd) is approved in some markets to delay neurologic progression in ATTR-PN, while high-dose tafamidis (80/61 mg po qd) is approved worldwide to reduce cardiovascular mortality and cardiovascular-related hospitalization in ATTR-CM. The objective of this study was to assess the real-world benefit of high-dose tafamidis for delaying neurologic progression in patients with mixed-phenotype variant ATTR-CM (ATTRv-CM). Methods This exploratory, retrospective, observational cohort study evaluated anonymized electronic medical records and included adult patients with mixed-phenotype ATTRv-CM treated with high-dose tafamidis for at least 6 months. Neurologic assessments included the Medical Research Council (MRC) Scale for Muscle Strength, Neuropathy Impairment Score (NIS) muscle weakness subscale, and Polyneuropathy Disability (PND) instrument. Modified body mass index (mBMI) was also assessed. Results Patients (N = 10) started tafamidis treatment an average of 3.8 months after diagnosis, with an average treatment duration of 20.8 months. Seven of 10 patients demonstrated normal muscle strength on the MRC scale throughout the study, and 9 of 10 patients had no decline in muscle strength during the post-treatment period. The NIS muscle weakness subscale score was ≤ 60 for all patients in the study at all time points, suggesting normal function to mild impairment. Six of 10 patients had no change in walking capacity as measured by the PND instrument at pre- and post-assessments, while one-third of patients had a decrease in PND stage (signaling improvement) from pre- to post-assessment. mBMI remained relatively stable throughout the study. Conclusion This is the first real-world study to demonstrate the potential value of high-dose tafamidis for delaying neurologic disease progression in patients with mixed-phenotype ATTRv-CM. The findings underscore the importance of multidisciplinary assessment for patients with ATTR amyloidosis. Trial registration ClinicalTrials.gov: NCT05139680. more...
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- 2024
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36. A clinical case of transthyretin amyloidosis with manifestations of seronegative arthritis
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V. A. Mareeva, A. A. Klimenko, E. R. Moskalets, P. A. Glazunov, N. A. Shostak, and E. V. Zhilyaev
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amyloidosis ,amyloid neuropathies ,transthyretin amyloidosis ,transthyretin ,carpal tunnel syndrome ,senile systemic amyloidosis ,radiopharmaceutical ,tafamidis ,radionuclide imaging ,quality of life ,Medicine - Abstract
Introduction. A clinical case of an 80-year-old patient with clinical and instrumental manifestations of amyloidosis caused by the deposition of non-mutant (“wild type”) transthyretin (Amyloidosis “wild type” TransThyRetin, ATTRwt) is described. A special feature of this case was the diagnosis of amyloidosis at the same time as the identification of symmetrical polyarthritis.Aim. To present an example of successful diagnosis and timely treatment of ATTRwt amyloidosis.Materials and methods. Male patient (80 years old) consulted a rheumatologist in an outpatient clinic with complaints of weakness and pain in the muscles of the upper and lower extremities, swelling and soreness of both wrist joints; with manifestations of multiple tunnel syndromes (ulnar canal, Guyon canals, bilateral carpal tunnel syndrome). In addition, the patient had a heart involvement which appeared as left ventricle hypertrophy, paroxysmal form of atrial fibrillation, chronic heart failure with preserved ejection fraction, intraventricular conduction defect and low QRS voltage. Due to the presence of cardiac manifestations along with neuropathy, transthyretinic amyloidosis was suspected.Results. Polyneuropathy was confirmed by the results of electroneuromyography. AL-amyloidosis (immunoglobulin Light chain Amyloidosis) is excluded due to the absence of monoclonal proteins in the blood. The diagnosis was confirmed by the results of scintigraphy with with labeled technetium-99m pyrophosphate. Intensive accumulation of radiopharmaceutical was detected in the myocardium of the left ventricle. The study also confirmed the presence of polyarthritis, manifested by increased accumulation, in the area of the I metatarsophalangeal joint on the left, both wrist, shoulder and knee joints. The hereditary nature of ATTR amyloidosis was excluded by the results of genetic analysis, which did not reveal mutations in the transthyretin gene. The singularity of this case was in development of a symmetrical polyarthritis during amyloidosis manifestation. Pathogenetic therapy with tafamidis was initiated. Arthritis regressed after starting treatment with methotrexate.Conclusion. Transthyretin amyloidosis is a chronic progressive life-threatening disease caused by the formation and deposition of transthyretin-derived amyloid fibrils. The variety of amyloid tropicity to various organs and tissues leads to it phenotypic heterogeneity, which makes it difficult to make a diagnosis on early stages. However, the detection of «red flags» symptoms signaling the presence of transthyretin amyloidosis can shorten the time before initiation of targeted treatment, contributing to the improvement of the patient’s quality of life. more...
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- 2024
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37. Experience with tafamidis in peritoneal dialysis for a patient diagnosed with transthyretin cardiac amyloidosis.
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Fazlic, Diego López, García, Samuel Abrante, Gerard, Micaela, Izquierdo, Edduin Martín, Bethencourt, Alejandro Alonso, Vannini, Luca, García, Celestino Hernández, and Heras, Manuel Macía
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PERITONEAL dialysis , *CHRONIC kidney failure , *KIDNEY failure , *HEMODIALYSIS , *TRANSTHYRETIN , *CARDIAC amyloidosis - Abstract
Cardiac amyloidosis is a cardiomyopathy resulting from the extracellular deposition of proteins such as transthyretin (TTR). We present the case of a 72-year-old male with hereditary cardiac amyloidosis. After confirming the diagnosis, tafamidis, a TTR stabilizer, was administered. Remarkably, tafamidis, when coupled with peritoneal dialysis for chronic kidney disease, maintained stability in both cardiac and renal functions. Previous studies have demonstrated the efficacy of tafamidis in reducing all-cause mortality and cardiovascular hospitalizations, although its use in severe renal failure lacks specific evaluation. This case suggests a potential application of tafamidis in moderate–severe kidney disease, emphasizing the need for further research in this population. [ABSTRACT FROM AUTHOR] more...
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- 2024
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38. Chest pain in a patient with transthyretin cardiac amyloidosis: A case report.
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Xie, Linfeng, Luo, Suxin, and Huang, Bi
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CARDIAC amyloidosis , *CHEST pain , *CARDIAC patients , *FATIGUE (Physiology) , *ANGINA pectoris , *TRANSTHYRETIN - Abstract
Key Clinical Message: Patients with transthyretin cardiac amyloidosis (ATTR‐CM) commonly present with dyspnea, fatigue, and edema. In our case, the main presentation was exertional angina, which was atypical in patients with ATTR‐CM and should be paid more attention to. A 54‐year‐old woman was admitted with a complaint of exertional chest pain, and she had a history of hypertension. The results of the electrocardiogram and echocardiography revealed the clues of cardiac amyloidosis, and the patient was finally diagnosed with transthyretin cardiac amyloidosis, then she received tafamidis, and the symptoms improved significantly. [ABSTRACT FROM AUTHOR] more...
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- 2024
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39. Effect of long‐term tafamidis treatment on health‐related quality of life in patients with transthyretin amyloid cardiomyopathy.
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Grogan, Martha, Davis, Margot K., Crespo‐Leiro, Maria G., Sultan, Marla B., Gundapaneni, Balarama, Stedile Angeli, Franca, and Hanna, Mazen
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QUALITY of life , *TRANSTHYRETIN , *AMYLOID , *CARDIOMYOPATHIES - Abstract
Aims: To evaluate the effect of long‐term tafamidis treatment on health‐related quality of life (HRQoL) in patients with transthyretin amyloid cardiomyopathy (ATTR‐CM) enrolled in the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR‐ACT) and long‐term extension (LTE) study. Methods and results: We examined change from baseline in Kansas City Cardiomyopathy Questionnaire overall summary (KCCQ‐OS) and clinical summary (KCCQ‐CS) scores in patients who received tafamidis meglumine 80 mg for 30 months in ATTR‐ACT and tafamidis (meglumine 80 mg or bioequivalent free acid 61 mg) for 30 months in the LTE study, and in patients who received placebo for 30 months in ATTR‐ACT and tafamidis for 30 months in the LTE study. In ATTR‐ACT, 176 and 177 patients were randomized to tafamidis 80 mg and placebo, respectively. Patients who continuously received tafamidis had a 6‐ to 7‐point reduction in least squares (LS) mean (standard error) KCCQ‐OS and KCCQ‐CS scores at month 30 (−6.25 [1.53] and −7.48 [1.39]), with little or no further decline over the next 30 months (−5.92 [1.77] and −9.21 [1.88] at month 60). Patients who received placebo in ATTR‐ACT had a 20‐point reduction in LS mean KCCQ‐OS and KCCQ‐CS scores at month 30 (−19.60 [1.94] and −19.90 [2.01]), but the decline slowed after initiating tafamidis (−24.70 [3.04] and −25.30 [3.36] at month 60). Conclusion: Tafamidis reduced HRQoL decline in patients with ATTR‐CM. Patients continuously treated with tafamidis for 60 months demonstrated stabilized HRQoL. In patients who initially received placebo in ATTR‐ACT, tafamidis reduced the decline in HRQoL during the LTE study. [ABSTRACT FROM AUTHOR] more...
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- 2024
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40. Reduction in 99mTc-DPD myocardial uptake with therapy of ATTR cardiomyopathy.
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Rettl, René, Calabretta, Raffaella, Duca, Franz, Binder, Christina, Kronberger, Christina, Willixhofer, Robin, Poledniczek, Michael, Donà, Carolina, Nitsche, Christian, Beitzke, Dietrich, Loewe, Christian, Auer-Grumbach, Michaela, Bonderman, Diana, Kastl, Stefan, Hengstenberg, Christian, Badr Eslam, Roza, Kastner, Johannes, Bergler-Klein, Jutta, Hacker, Marcus, and Kammerlander, Andreas more...
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SINGLE-photon emission computed tomography , *COMPUTED tomography - Abstract
Aims: Novel ribonucleic acid interference (RNAi) therapeutics such as patisiran and inotersen have been shown to benefit neurologic disease course and quality of life in patients with hereditary transthyretin amyloidosis (ATTRv). We aimed to determine the impact of RNAi therapeutics on myocardial amyloid load using quantitative single photon emission computed tomography/computed tomography (SPECT/CT) imaging in patients with ATTRv-related cardiomyopathy (ATTRv-CM). We furthermore compared them with wild-type ATTR-CM (ATTRwt-CM) patients treated with tafamidis. Methods and results: ATTRv-CM patients underwent [99mTc]-radiolabeled diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) scintigraphy and quantitative SPECT/CT imaging before and after 12 months (IQR: 11.0–12.0) of treatment with RNAi therapeutics (patisiran: n = 5, inotersen: n = 4). RNAi treatment significantly reduced quantitative myocardial uptake as measured by standardised uptake value (SUV) retention index (baseline: 5.09 g/mL vs. follow-up: 3.19 g/mL, p =.028) in ATTRv-CM patients without significant improvement in cardiac function. Tafamidis treatment resulted in a significant reduction in SUV retention index (4.96 g/mL vs. 3.27 g/mL, p <.001) in ATTRwt-CM patients (historical control cohort: n = 40) at follow-up [9.0 months (IQR: 7.0–10.0)] without beneficial impact on cardiac function. Conclusions: RNAi therapeutics significantly reduce quantitative myocardial uptake in ATTRv-CM patients, comparable to tafamidis treatment in ATTRwt-CM patients, without impact on cardiac function. Serial 99mTc-DPD SPECT/CT imaging may be a valuable tool to quantify and monitor response to disease-specific therapies in both ATTRv-CM and ATTRwt-CM. [ABSTRACT FROM AUTHOR] more...
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- 2024
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41. Outcomes in Cardiac Transthyretin Amyloidosis and Association With New York Heart Association Class: Real‐World Data
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Maximilian Leo Müller, Ekaterina Latinova, Anna Brand, Isabel Mattig, Sebastian Spethmann, Daniel Messroghli, Katrin Hahn, Ulf Landmesser, and Bettina Heidecker
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cardiac transthyretin amyloidosis ,NYHA ,tafamidis ,transthyretin amyloid cardiomyopathy ,transthyretin amyloidosis ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background Results from ATTR‐ACT (Safety and Efficacy of Tafamidis in Patients With Transthyretin Cardiomyopathy) indicate that tafamidis prolongs survival and reduces cardiovascular hospitalizations in cardiac transthyretin amyloidosis (ATTR‐CA). However, real‐world data supporting these findings are scarce. Thus, we sought to characterize the clinical outcome of patients with ATTR‐CA treated with tafamidis in a real‐world setting and assess the prognostic role of the New York Heart Association (NYHA) classification. Methods and Results We conducted a retrospective observational study, enrolling a consecutive sample of patients with ATTR‐CA (wild‐type or variant) treated with tafamidis. Clinical outcome was tracked through follow‐up visits or phone calls. Primary outcomes were death and major adverse cardiac events (MACE), a composite end point of death and hospitalizations for acute cardiac decompensation, myocardial infarction, severe arrythmias, or stroke. Kaplan‐Meier analysis estimated overall and MACE‐free survival including NYHA subgroups (NYHA I/II versus NYHA III). One hundred sixty‐seven patients with ATTR‐CA (94.6% wild‐type) were enrolled and followed for a median of 539 [323–869] days. Median overall survival was not reached. Estimated 1‐year, 2‐year, and 5‐year overall survival among the whole cohort was 93.5%, 85.9%, and 70.2%, respectively. Overall survival was higher in the NYHA I/II subgroup (P=0.002). Median MACE‐free survival time was 1082 (95% CI, 962–1202) days. MACE‐free survival was higher in the NYHA I/II subgroup (P more...
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- 2024
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42. Cardiac Biomarker Change at 1 Year After Tafamidis Treatment and Clinical Outcomes in Patients With Transthyretin Amyloid Cardiomyopathy
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Naoto Kuyama, Seiji Takashio, Tetsuya Oguni, Masahiro Yamamoto, Kyoko Hirakawa, Masanobu Ishii, Shinsuke Hanatani, Seitaro Oda, Yasushi Matsuzawa, Hiroki Usuku, Eiichiro Yamamoto, Toshinori Hirai, Mitsuharu Ueda, and Kenichi Tsujita more...
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B‐type natriuretic peptide ,high‐sensitivity cardiac troponin T ,tafamidis ,wild‐type transthyretin amyloid cardiomyopathy ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background Although tafamidis treatment improves prognosis in patients with wild‐type transthyretin amyloid cardiomyopathy, an optimal surrogate marker monitoring its therapeutic effect remains unclear. This study investigated the association between changes in cardiac biomarkers, high‐sensitivity cardiac troponin T (hs‐cTnT) and B‐type natriuretic peptide (BNP) during the first year after tafamidis treatment and clinical outcomes. Methods and Results In 101 patients with wild‐type transthyretin amyloid cardiomyopathy receiving tafamidis at our institution, change in cardiac biomarkers from baseline to 1 year after tafamidis administration and its association with composite outcomes (composite of all‐cause death and hospitalization attributable to heart failure) was assessed. During the follow‐up period (median, 17 months), 16 (16%) patients experienced composite outcomes. The hs‐cTnT level significantly decreased at 1 year after tafamidis treatment, unlike the BNP level. The frequencies of increased hs‐cTnT and BNP levels were significantly higher in those with composite outcomes than in those without (44% versus 15%; P=0.01). Kaplan‐Meier survival analysis showed that patients in whom both hs‐cTnT and BNP levels increased at 1 year after tafamidis had a higher probability of composite outcomes compared with those with decreased hs‐cTnT and BNP levels (log‐rank P more...
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- 2024
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43. Tafamidis decreased cardiac amyloidosis deposition in patients with Ala97Ser hereditary transthyretin cardiomyopathy: a 12-month follow-up cohort study
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Cheng-Hsuan Tsai, Chi-Chao Chao, Sung-Tsang Hsieh, An-Li Yu, Yuan-Kun (Aden) Wu, Mei-Fang Cheng, Ming-Jen Lee, Chia-Hung Chou, Chia-Tung Shun, Hsueh-Wen Hsueh, Jimmy Jyh-Ming Juang, Ping-Huei Tseng, Mao-Yuan Su, and Yen-Hung Lin more...
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Cardiac magnetic resonance ,Extracellular volume ,Hereditary transthyretin amyloidosis ,Tafamidis ,Medicine - Abstract
Abstract Background Transthyretin cardiac cardiomyopathy (ATTR-CM) is a rare but life-threatening disease. Tafamidis is an effective treatment for patients with ATTR-CM, however its long-term effects on cardiac remodeling and cardiac amyloid deposition are unknown. This study aimed to used cardiac magnetic resonance (CMR) to investigate the effects of tafamidis on patients with hereditary A97S ATTR-CM. Methods We retrospectively analyzed a prospective cohort of ATTR-CM patients, including 14 with hereditary A97S ATTR-CM and 17 healthy controls with baseline CMR data. All ATTR-CM patients received tafamidis treatment and received CMR with extracellular volume (ECV) at baseline and after 1 year of follow-up. Results Baseline N-terminal pro-B-type natriuretic peptide, left ventricular (LV) mass, LV ejection fraction, global radial, circumferential and longitudinal strain, T1 mapping and ECV were significantly worse in the patients with ATTR-CM compared with the healthy controls. After 1 year of tafamidis treatment, ECV decreased from 51.5 ± 8.9% to 49.0 ± 9.4% (P = 0.041), however there were no significant changes in LV mass, LV ejection fraction, global radial strain, global circumferential strain, global longitudinal strain and T1 mapping. Conclusions After a one-year treatment period, tafamidis exhibited subtle but statistically significant reductions in ECV, potentially indicating a decrease in amyloid deposition among patients diagnosed with hereditary A97S ATTR-CM. more...
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- 2023
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44. Clinical characteristics, outcome, and therapeutic effect of tafamidis in wild‐type transthyretin amyloid cardiomyopathy
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Seiji Takashio, Mami Morioka, Masanobu Ishii, Kei Morikawa, Kyoko Hirakawa, Shinsuke Hanatani, Fumi Oike, Hiroki Usuku, Masafumi Kidoh, Seitaro Oda, Eiichiro Yamamoto, Kenichi Matsushita, Mitsuharu Ueda, and Kenichi Tsujita more...
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Transthyretin amyloid cardiomyopathy ,Tafamidis ,Prognosis ,Biomarkers ,Imaging ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
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 0.05 ng/mL, B‐type natriuretic peptide (BNP) > 250 pg/mL, and estimated glomerular filtration rate (eGFR) more...
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- 2023
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45. Chest pain in a patient with transthyretin cardiac amyloidosis: A case report
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Linfeng Xie, Suxin Luo, and Bi Huang
- Subjects
chest pain ,Tafamidis ,Technetium‐99m pyrophosphate ,transthyretin cardiac amyloidosis ,Medicine ,Medicine (General) ,R5-920 - Abstract
Key Clinical Message Patients with transthyretin cardiac amyloidosis (ATTR‐CM) commonly present with dyspnea, fatigue, and edema. In our case, the main presentation was exertional angina, which was atypical in patients with ATTR‐CM and should be paid more attention to. Abstract A 54‐year‐old woman was admitted with a complaint of exertional chest pain, and she had a history of hypertension. The results of the electrocardiogram and echocardiography revealed the clues of cardiac amyloidosis, and the patient was finally diagnosed with transthyretin cardiac amyloidosis, then she received tafamidis, and the symptoms improved significantly. more...
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- 2024
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46. Multiparametric Monitoring of Disease Progression in Contemporary Patients with Wild-Type Transthyretin Amyloid Cardiomyopathy Initiating Tafamidis Treatment.
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Ney, Svenja, Gertz, Roman Johannes, Pennig, Lenhard, Nies, Richard J., Holtick, Udo, Völker, Linus A., Wunderlich, Gilbert, Seuthe, Katharina, Hohmann, Christopher, Metze, Clemens, Nähle, Claas Philip, von Stein, Jennifer, Brüwer, Monique, ten Freyhaus, Henrik, and Pfister, Roman more...
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GLOBAL longitudinal strain , *CEREBRAL amyloid angiopathy , *DISEASE progression , *CARDIAC magnetic resonance imaging , *TRANSTHYRETIN , *AMYLOID - Abstract
Background: Recently, a disease modifying therapy has become available for transthyretin amyloid cardiomyopathy (ATTR-CM). A validated monitoring concept of treatment is lacking, but a current expert consensus recommends three clinical domains (clinical, biomarker and ECG/imaging) assessed by several measurable features to define disease progression. Methods: We retrospectively analyzed data of wild-type ATTR-CM patients initiating tafamidis therapy assessed within our local routine protocol at baseline and 6-months follow-up with respect to the frequency of values beyond the proposed thresholds defining disease progression. Additionally, associations of cardiac magnetic resonance (CMR) tomography with clinical domains were examined within a subgroup. Results: Sixty-two ATTR-CM patients were included (88.7% male, mean age 79 years). In total, 16.1% of patients had progress in the clinical and functional domain, 33.9% in the biomarker domain and 43.5% in the imaging/electrocardiography (ECG) domain, with the latter driven by deterioration of the diastolic dysfunction grade and global longitudinal strain. In total, 35.5% of patients showed progress in none, 35.5% in one, 29.0% in two and no patient in three domains, the latter indicating overall disease progression. A subgroup analysis of twenty-two patients with available baseline and follow-up CMR data revealed an increase in CMR-based extracellular volume by more than 5% in 18.2% of patients, with no significant correlation with progress in one of the clinical domains. Conclusions: We provide first frequency estimates of the markers of disease progression according to a recent expert consensus statement, which might help refine the multiparametric monitoring concept in patients with ATTR-CM. [ABSTRACT FROM AUTHOR] more...
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- 2024
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47. Tafamidis Drug Delivery Systems Based on Chitosan/Polyvinyl Alcohol Matrix †.
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Snetkov, Petr, Generalova, Yuliya, Vu, Thi Hong Nhung, Morozkina, Svetlana, and Uspenskaya, Mayya
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CARDIOVASCULAR agents ,DRUG delivery systems ,POLYVINYL alcohol ,CHITOSAN ,CARDIAC amyloidosis - Abstract
Cardiovascular diseases retain their position as the leading cause of death globally, and according to the World Health Organization, there are 17.9 million cases of these diseases each year. Cardiac amyloidosis caused by the formation and deposition of a specific protein–polysaccharide complex–amyloid in the myocardium represents the main cause of death. The pharmaceutical molecules clinically used against amyloidosis are very limited; currently, there are only two non-selective hydrophobic agents—diflunisal and tafamidis. In addition to the non-selective mode of action of both drugs, tafamidis, with greater therapeutic efficacy, is the most expensive: the yearly course costs appr. USD 225,000. One of the possible ways of enhancing its solubility and bioavailability, decreasing the dosage with the simultaneous targeted effect, is the encapsulation of the drug into polymer (biopolymer) matrixes. In contrast to the known diflunisal delivery systems, there are no available data on the development of tafamidis delivery systems. In this study, we report, for the first time, a method for the encapsulation of tafamidis into a polymeric matrix based on the mixture of chitosan and polyvinyl alcohol (PVA). The release profile of the polymer matrix was analyzed, and no burst characteristic was demonstrated. The obtained tafamidis-loaded polymer matrixes based on biosafe and biocompatible polymers require further investigations in vitro and in vivo to evaluate their potential for clinical application. [ABSTRACT FROM AUTHOR] more...
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- 2023
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48. Variation of tafamidis plasma levels during the treatment of TTR amyloidosis patients with Glu89Gln mutation.
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Smerikarova, M., Bozhanov, S., Tournev, I., and Maslarska, V.
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GLUTAMIC acid , *RESEARCH , *AMYLOIDOSIS , *GENETIC mutation , *HIGH performance liquid chromatography , *SCIENTIFIC observation , *HETEROCYCLIC compounds , *AGE distribution , *TREATMENT duration , *SERUM albumin , *INTER-observer reliability , *SEX distribution , *DESCRIPTIVE statistics , *DRUG monitoring , *GLUTAMINE , *STATISTICAL correlation , *LONGITUDINAL method ,RESEARCH evaluation - Abstract
Purpose: The transthyretin kinetic stabilizer tafamidis, used as a first-line therapy of amyloidosis patients, binds selectively to the transthyretin protein structure and thus prevents its dissociation. The limited information regarding tafamidis application in Glu89Gln amyloidosis patients imposed our research team to determine and evaluate its individual mean plasma levels and their biological variation. Methods: The present cohort study investigated Bulgarian amyloidosis patients, grouped by gender, age, and therapy duration. A total of sixty patients aged 40–75 years and therapy duration up to 9 years were included. A precise and accurate high-performance liquid chromatography method with ultraviolet detection was used for plasma concentration measurement. Results: Mean plasma concentrations were 5.13 ± 2.64 µmol/L and showed low intra-individual (18.50%) and high inter-individual variability (51.43%). No significant difference was observed between tafamidis plasma levels and therapy duration with p = 0.5941 (p < 0.05 considered significant), but a significant positive correlation was found between plasma concentration, gender, and age with obtained results about p-value 0.0001 and 0.0235, respectively. Conclusion: The summary results of the study showed differences that may be based on some specific clinical features of the Glu89Gln mutation. [ABSTRACT FROM AUTHOR] more...
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- 2023
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49. Croatian Transthyretin Cardiac Amyloidosis Registry - an update.
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Šipuš, Dubravka, Lozo, Emilija Katarina, Lončarić, Filip, Fabijanović, Dora, Jakuš, Nina, Pašalić, Marijan, Jurin, Hrvoje, Samardžić, Jure, Skorić, Boško, Lovrić, Daniel, Miličić, Davor, Borovečki, Fran, Vodušek, Maja Čikeš, and Planinc, Ivo more...
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NATRIURETIC peptides , *CHRONIC kidney failure , *HEART failure patients , *BRAIN natriuretic factor , *CARDIAC amyloidosis , *AORTIC stenosis - Abstract
Introduction: The Croatian Transthyretin Cardiac Amyloidosis (CroATTR) Registry was founded in September 2022 to acquire demographic characteristics and follow clinical outcomes including echocardiographic, electrocardiographic and laboratory data of patients with wild type (wtATTR) or hereditary (hATTR) transthyretin cardiac amyloidosis as well as their family members with confirmed mutation of the TTR gene. Patients and Methods: We analyzed data collected retrospectively and prospectively of 48 patients included in CroATTR. Descriptive statistics methods were used to analyze the data. Results: Of 48 patients included in CroATTR, 8 have hATTR, 34 wtATTR and 6 were phenotype negative with confirmed mutation of TTR gene. Eight hATTR patients were male, with median age 50 years (range 43-66 years). Seven have Asp18Glu mutation, while one has Val30Met mutation. Three have received heart and liver transplantation (Tx), of them two concomitant heart and liver Tx. One patient has died 5 years after heart Tx. Remaining 5 patients are treated with tafamidis. Of 34 wtATTR patients 58% are male, with median age 75.5 years (range 45-86 years). Most of the patients have several comorbidities: 79% have arterial hypertension, 38% have chronic kidney disease, 74% have atrial fibrillation, 23% have implanted pacemaker and 18% have aortic stenosis. Twenty-eight patients are on tafamidis treatment, of which 16 are on tafamidis for longer than 6 months. There is tendency to lower NTproBNP (prior to tafamidis treatment median NTproBNP 2263 ng/L, range 495-12531 ng/L, after 6 months median NTproBNP 2251 ng/L, range 349-9574 ng/L) and better 6-minute walk test results (prior to tafamidis median length 335 m, range 160-480 m, after 6 months median length 420 m, range 250-495 m) with tafamidis treatment. Three patients died of heart failure, and one has had heart failure admission. All six phenotype negative patients with confirmed mutation of TTR gene have Asp18Glu mutation. In 2 years of follow-up one patient has developed early signs of cardiomyopathy. Complete patients’ data are shown in Table 1. Conclusion: CroATTR is designed to increase knowledge about ATTR-CM and to follow treatment with specific therapy. According to the current data, there are signs of lower natriuretic peptides and better 6-minute walk test results in patients treated with tafamidis. [ABSTRACT FROM AUTHOR] more...
- Published
- 2024
- Full Text
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50. A case of disappearing amyloid on technetium pyrophosphate scan.
- Author
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Wang, Andy, Mahmood, Uzair, Tang, Xiaoyu, Jain, Diwakar, and Pan, Stephen
- Abstract
Technetium-99mm pyrophosphate (Tc-PYP) scintigraphy is a highly accurate non-invasive method for the diagnosis of transthyretin (ATTR) cardiac amyloidosis. Prognosis for this disease is improved following treatment with the transthyretin (TTR) stabilizer tafamidis. Although tafamidis slows disease progression, its effects on myocardial amyloid and Tc-PYP uptake remain unclear. We present a patient with ATTR cardiac amyloidosis who had a strongly positive initial Tc-PYP scan, with a dramatic decrease in Tc-PYP uptake on repeat scan after 3 years of tafamidis treatment. However, myocardial biopsy showed persistent diffuse amyloid deposits. This case highlights the need for further studies regarding the utility of serial Tc-PYP scans in monitoring the progress of ATTR cardiomyopathy. [ABSTRACT FROM AUTHOR] more...
- Published
- 2023
- Full Text
- View/download PDF
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