Cardiology and Therapy最新文献

{"title":"Polyneuropathy Assessment and Treatment Patterns in Patients with Hereditary Transthyretin Amyloidosis.","authors":"Nicholas Streicher, Hermela Wubet","doi":"10.1007/s40119-026-00472-6","DOIUrl":"10.1007/s40119-026-00472-6","url":null,"abstract":"<p><strong>Introduction: </strong>Hereditary transthyretin amyloidosis (hATTR) manifests as cardiomyopathy and/or polyneuropathy. Polyneuropathy may be suspected for a variety of reasons, but the clinical evidence supporting that impression varies. We used International Classification of Diseases, Tenth Revision (ICD-10) coding to broadly capture patients thought to have polyneuropathy in a V142I-predominant cohort and examined what clinical documentation actually supported the diagnosis and whether documentation level influences treatment selection.</p><p><strong>Methods: </strong>Retrospective chart review of 54 patients identified by co-occurring ICD-10 codes for transthyretin amyloidosis and polyneuropathy at a major academic medical center, with pathogenic TTR variant confirmation. Polyneuropathy codes were then classified by the level of clinical evidence supporting the diagnosis. Treatment with TTR stabilizers and gene silencers was assessed.</p><p><strong>Results: </strong>Of 54 patients (90.7% non-Hispanic Black, 87.0% V142I), 51 (94.4%) had confirmed cardiac involvement with 40/42 eligible (95.2%) receiving stabilizers. Sixteen patients (29.6%) received gene silencers, with 11 receiving both concurrently. Clinical evidence supporting the polyneuropathy code was identified in 43 patients (79.6%): ancillary testing confirmation in 18 (33.3%), provider documentation without ancillary testing in 14 (25.9%), and symptoms only in 11 (20.4%). The remaining 11 (20.4%) had insufficient documentation to support the code. Gene silencer use was highest among those with ancillary testing (50.0%) versus symptoms only (18.2%).</p><p><strong>Conclusion: </strong>Among patients with hATTR coded for polyneuropathy, only 33.3% had ancillary testing confirmation. Gene silencer use tracked with documentation quality rather than the presence of a code alone. These findings highlight the gap between administrative coding and clinical documentation and support standardized neurological assessment in hATTR.</p>","PeriodicalId":9561,"journal":{"name":"Cardiology and Therapy","volume":" ","pages":"365-375"},"PeriodicalIF":3.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13542013/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148849852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Defining Heart Failure Endpoint in ATTR Amyloidosis Clinical Trials: Time for an Update?","authors":"Diona Gjermeni, Kevin M Alexander, James L Januzzi, Kenneth W Mahaffey","doi":"10.1007/s40119-026-00462-8","DOIUrl":"10.1007/s40119-026-00462-8","url":null,"abstract":"<p><p>This viewpoint highlights the critical need for a standardized definition of heart failure (HF) endpoints in clinical trials specific to transthyretin cardiac amyloidosis (ATTR-CA). Current endpoint definitions vary significantly across standard HF and amyloidosis trials. The objective of this viewpoint is to support clinical trialists by providing practical considerations on how to better define HF events when designing amyloidosis clinical trials, as well as during the adjudication process. We suggest defining HF events based on three major components: acute hospitalizations or inpatient visits for HF, urgent outpatient HF visits, and recurrent outpatient visits. By refining these definitions, we aim to create a framework that accurately reflects the complexities of HF in amyloidosis and promotes consistency in endpoint definitions or HF event adjudication.</p>","PeriodicalId":9561,"journal":{"name":"Cardiology and Therapy","volume":" ","pages":"265-279"},"PeriodicalIF":3.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13542036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148429824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The 'Chloride Theory' for Heart Failure Pathophysiology: An Updated Narrative Review 2025.","authors":"Hajime Kataoka","doi":"10.1007/s40119-026-00460-w","DOIUrl":"10.1007/s40119-026-00460-w","url":null,"abstract":"<p><p>Most studies of heart failure (HF) syndromes have focused on fluid regulation, particularly the balance of sodium and water. Approximately 10 years ago, in 2017, the \"chloride theory\" was proposed as a unifying hypothesis, suggesting that changes in serum chloride concentration are associated with shifts in plasma volume, hemodynamics, and neurohormonal activity during HF progression and treatment. This narrative review updates the chloride theory based on emerging clinical evidence. It further examines diuretic classification from a chloride-centered perspective, recent advances in guideline-directed medical therapy, and the potential role of chloride in loop diuretic resistance and its management. In addition, the review summarizes the prognostic relevance of changes in serum chloride during acute HF and the distinct pathophysiologic roles of sodium and chloride. Overall, this review provides an integrated perspective on HF pathophysiology, therapeutic strategies, and clinical monitoring within a chloride-centered framework.</p>","PeriodicalId":9561,"journal":{"name":"Cardiology and Therapy","volume":" ","pages":"407-438"},"PeriodicalIF":3.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13542041/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148403740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond LDL-C: Modern Lipid Management for ASCVD Prevention in Primary Care.","authors":"Andrew Carlson, Zaid A Zayyad, Stefanie Driesenga, Peter Boxley, Atreya Mishra, Omar Uraizee, Rediat Ephrem, Runze Zhang, Zachary Natsheh, Adhir R Shroff","doi":"10.1007/s40119-026-00473-5","DOIUrl":"10.1007/s40119-026-00473-5","url":null,"abstract":"<p><p>Prevention of atherosclerotic cardiovascular disease (ASCVD) is fundamental for both cardiologists and primary care physicians. From risk estimation to medical therapy for primary and secondary prevention, management is evolving with increasing evidence. Risk estimation is moving toward a model that emphasizes lifetime risk in addition to traditional shorter-term risk and takes a holistic view of individual patient cardiovascular risk, accounting for genetic predisposition and risk-enhancing comorbid conditions. Lipoprotein(a) and apolipoprotein B measurement and coronary artery calcification (CAC) scoring have emerged as tools for identifying residual risk and making decisions in cases of borderline risk. While statins remain foundational to management, newer treatment paradigms emphasize early intensification of therapy and addition of non-statin agents. These trends are reflected in recent guideline updates from the American College of Cardiology/American Heart Association (ACC/AHA) and European Society of Cardiology/European Atherosclerosis Society (ESC/EAS). In the future, polygenic risk scoring and RNA-based therapies may offer opportunities to identify and treat those at highest residual risk.</p>","PeriodicalId":9561,"journal":{"name":"Cardiology and Therapy","volume":" ","pages":"481-501"},"PeriodicalIF":3.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13542026/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148788461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rationale and Design of ACO-REAL: A Real-World Non-Interventional Study of Acoramidis in Routine Clinical Practice.","authors":"Marianna Fontana, Francesco Cappelli, Julian D Gillmore, Laura Obici, Fabian Aus dem Siepen, Philippe Debonnaire, Esther Gonzalez-Lopez, Marcel Schulze, Kai Vogtländer, Antonio Ciaccia, Martin Merz, Pablo Garcia-Pavia","doi":"10.1007/s40119-026-00461-9","DOIUrl":"10.1007/s40119-026-00461-9","url":null,"abstract":"<p><strong>Introduction: </strong>Acoramidis, an oral transthyretin stabilizer that achieves near-complete stabilization, is approved for the treatment of transthyretin amyloid cardiomyopathy (ATTR-CM) based on the phase 3 study, ATTRibute-CM (NCT03860935). To complement trial data, ACO-REAL (NCT07235462) was designed to generate real-world evidence on acoramidis use in ATTR-CM. This article describes the rationale and design of ACO-REAL.</p><p><strong>Methods: </strong>ACO-REAL is an ongoing, prospective, non-interventional, multicenter study planned in approximately 2000 adults with ATTR-CM (wild-type or variant) initiating treatment with acoramidis in real-world settings across 21 European countries. The primary objective of ACO-REAL is to assess the characteristics and treatment patterns of participants with ATTR-CM receiving acoramidis during an observational period of around 12 months.</p><p><strong>Planned outcomes: </strong>The primary objective is to assess demographics (including age and sex), disease characteristics, and treatment patterns of participants treated with acoramidis. Disease characteristics include type, diagnosis, and manifestations of ATTR-CM, and ATTR-CM-relevant comorbidities. Treatment patterns include adherence, persistence, and reasons for treatment modifications, including switching from a different ATTR-CM medication to acoramidis. The secondary objective is to describe the safety profile of acoramidis. The clinical course of ATTR-CM in participants initiating acoramidis is also being evaluated through measuring cardiac function, functional capacity and health status (New York Heart Association classification and 6-min walk distance), and health-related quality of life (Kansas City Cardiomyopathy Questionnaire and EuroQol 5-Dimension 5-Level questionnaire). Healthcare resource utilization is also being evaluated. Statistical analyses will be exploratory and descriptive. Categorical variables will be presented as frequencies and continuous variables as sample statistics.</p><p><strong>Conclusions: </strong>ACO-REAL is the first multinational observational study to collect regular, prospective, real-world data in participants with ATTR-CM treated with acoramidis. This study aims to provide insights into ATTR-CM treatment using real-world evidence from European healthcare systems and may help to guide decision-making in clinical practice. Graphical abstract available for this article.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier, NCT07235462.</p>","PeriodicalId":9561,"journal":{"name":"Cardiology and Therapy","volume":" ","pages":"515-528"},"PeriodicalIF":3.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13542039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148629512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Patient and Physician Perspective of Chronic Coronary Syndrome and Persistent Stable Angina in Brazil.","authors":"Antônio Figueiredo Araújo, Aparecida de Fátima Machado Tavares, Luís Henrique Wolff Gowdak","doi":"10.1007/s40119-026-00455-7","DOIUrl":"10.1007/s40119-026-00455-7","url":null,"abstract":"<p><p>Obstructions in the coronary arteries, arterial vasospasm, and microcirculation dysfunction may cause chronic coronary syndrome (CCS). Angina is a cardinal symptom of CCS and the journey of patients with angina is often filled with challenges and uncertainties. Diagnosis and treatment differences seem to vary between men and women with angina. This article is co-authored by a male and a female patient diagnosed with persistent stable angina and their treating cardiologist at the Heart Institute in São Paulo, Brazil. The patients share their personal experiences of more than 20 years of coping with pain and the related impact on their physical capacity, thus illustrating the challenging journey often faced by individuals with angina and how it differs between men and women. They describe the long pathway from the onset of symptoms to the correct diagnosis and list the various interventional procedures they underwent, focusing on the impact of angina on their daily lives. They also mention their participation in a clinical study. The cardiologist discusses the critical elements in the diagnostic process of angina, and reflects on how the misconception that heart disease primarily affects men can lead to delayed diagnosis and treatment for women suffering from this condition. Moreover, he emphasizes that many patients experience angina due to myocardial ischemia without obstructive coronary artery disease, highlighting the need to raise disease awareness among healthcare professionals, as well as in society. Finally, the physician underscores the importance of better patient assessment and medical treatment optimization to managing angina and meeting patients' needs and expectations, while prioritizing patient quality of life.</p>","PeriodicalId":9561,"journal":{"name":"Cardiology and Therapy","volume":" ","pages":"255-264"},"PeriodicalIF":3.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13542022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148275959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Tafamidis on Transthyretin Concentration and Its Relation to All-Cause Mortality in Patients with Transthyretin Amyloid Cardiomyopathy: An Analysis from ATTR-ACT.","authors":"Mathew S Maurer, Perry Elliott, Jeffery W Kelly, Mazen Hanna, Evan T Powers, Steve Riley, Rong Wang, Pablo Garcia-Pavia","doi":"10.1007/s40119-026-00468-2","DOIUrl":"https://doi.org/10.1007/s40119-026-00468-2","url":null,"abstract":"<p><strong>Introduction: </strong>Tafamidis is approved to treat transthyretin amyloid cardiomyopathy (ATTR-CM) on the basis of results of the phase 3 study ATTR-ACT. This post hoc analysis from ATTR-ACT evaluated the effect of tafamidis on transthyretin (TTR) concentration and explored the potential relationship between changes in TTR concentration at month 1 (early ΔTTR) and all-cause mortality (ACM).</p><p><strong>Methods: </strong>Patients with ATTR-CM treated with tafamidis 80 mg or placebo in ATTR-ACT who survived until month 1 were included. The independent association between early ΔTTR and ACM at month 30 was evaluated using univariate analyses, including a logistic model for ACM incidence and a Cox model for time to ACM. Baseline variables significantly influencing this relationship were identified using backward selection and included as covariates (baseline TTR concentration and National Amyloidosis Centre stage) in a multivariable Cox model.</p><p><strong>Results: </strong>Tafamidis 80 mg produced a 36.3% mean increase in TTR concentration by month 1 (mean [SD] change 7.3 [3.9] mg/dL) that was sustained through month 30, whereas placebo showed minimal change at month 1 (mean change [SD] - 0.02 [2.9] mg/dL) and throughout the study period. Logistic regression showed early ΔTTR was associated with reduced odds of ACM by month 30 only in patients treated with tafamidis; every 5 mg/dL increase correlated with a 45.0% reduction in odds of ACM (p = 0.0193). In univariate analysis, every 1 mg/dL increase in TTR concentration at month 1 in patients treated with tafamidis was associated with a 9.3% hazard reduction in ACM (hazard ratio 0.907; 95% CI 0.837-0.983, p = 0.0174). Multivariable analysis showed an 8.7% reduction in hazard of ACM for each 1 mg/dL increase.</p><p><strong>Conclusions: </strong>Tafamidis was associated with an early increase in TTR concentration that was sustained through month 30, and early increases correlated with reduced ACM. However, mechanisms underlying TTR concentration increases and their clinical significance remain unclear. Graphical abstract available for this article.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier NCT01994889.</p>","PeriodicalId":9561,"journal":{"name":"Cardiology and Therapy","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148839122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Survival in a Contemporary, Real-World, Matched Cohort of Patients with Transthyretin Amyloid Cardiomyopathy Treated vs Not Treated with Tafamidis.","authors":"Fabian Aus dem Siepen, Angela Dispenzieri, Mazen Hanna, Martin Carlsson, Pablo Garcia-Pavia","doi":"10.1007/s40119-026-00464-6","DOIUrl":"https://doi.org/10.1007/s40119-026-00464-6","url":null,"abstract":"<p><strong>Introduction: </strong>Tafamidis is approved for the treatment of transthyretin amyloid cardiomyopathy (ATTR-CM) and has shown a survival benefit in the phase 3 study ATTR-ACT and in real-world settings. This analysis compared survival in a contemporary, matched, real-world cohort of patients with ATTR-CM treated with tafamidis vs untreated.</p><p><strong>Methods: </strong>Data were pooled from an early access cohort (NCT02791230) and from patients enrolled in the Transthyretin Amyloidosis Outcomes Survey (THAOS; NCT00628745) in 2019-2023 with a mixed or predominantly cardiac phenotype. Propensity score matching (1:1) was performed to match treated and untreated patients in the pooled sample based on baseline age, New York Heart Association class, and phenotype. Treated patients received tafamidis at the approved dose for ATTR-CM.</p><p><strong>Results: </strong>A total of 283 treated and 283 untreated patients were included. Of the 283 treated patients, 85 were from the early access cohort and 198 from THAOS. All untreated patients were from THAOS. In treated vs untreated patients, mean age at enrollment was 76.9 vs 77.4 years, 89.0% vs 83.4% were male, 11.0% vs 16.6% were female, and 80.9% vs 73.1% had wild-type ATTR-CM. Estimated adjusted survival probabilities for all-cause mortality for treated vs untreated patients were 90.2% vs 76.0% at 30 months and 85.3% vs 67.5% at 42 months. Treated patients had a 74% lower risk of all-cause mortality compared with untreated patients (hazard ratio 0.26; 95% confidence interval 0.13-0.51). No new safety signals were identified.</p><p><strong>Conclusions: </strong>This matched-cohort analysis demonstrated improved survival in a contemporary, real-world cohort of patients with ATTR-CM receiving the approved dose of tafamidis compared with those untreated. These findings further extend the results of ATTR-ACT to contemporary populations of patients with ATTR-CM treated clinically with tafamidis and reinforce earlier real-world evidence supporting tafamidis use.</p><p><strong>Trial registration: </strong>Clinicaltrials.gov identifiers NCT00628745 and NCT02791230.</p>","PeriodicalId":9561,"journal":{"name":"Cardiology and Therapy","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148839249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional Stability Measured by Changes in the 6-min Walk Test in Patients Treated with Tafamidis Versus Placebo: Post hoc Analysis from ATTR-ACT.","authors":"Ronald Witteles, Mazen A Hanna, Martha Grogan, Perry Elliott, Ronnie Wang, Pablo Garcia-Pavia","doi":"10.1007/s40119-026-00471-7","DOIUrl":"https://doi.org/10.1007/s40119-026-00471-7","url":null,"abstract":"<p><strong>Introduction: </strong>Tafamidis, a transthyretin stabilizer for the treatment of transthyretin amyloid cardiomyopathy (ATTR-CM), significantly reduced the decline in 6-min walk test (6MWT) distance, a marker of functional stability, compared with placebo in the pivotal study ATTR-ACT. In this post hoc analysis, functional stability was assessed at month 12, and the subsequent impact of treatment on all-cause mortality (ACM) and cardiovascular-related hospitalization (CVH) was examined.</p><p><strong>Methods: </strong>Patients alive at month 12 who received tafamidis meglumine 80 mg (n = 149) or placebo (n = 149) were categorized by month 12 changes in 6MWT distance: stability (≤ 35-m decline from baseline) or progression (> 35-m decline from baseline). ACM and CVH rates during months 12-30 were evaluated using Cox proportional hazard and Poisson regression models, respectively.</p><p><strong>Results: </strong>A greater proportion of patients treated with tafamidis had 6MWT stability at month 12 (64%) vs. placebo (53%). Month 30 ACM incidence was 12% and 34% with 6MWT stability and progression, respectively, in the tafamidis group and 28% and 43%, respectively, in the placebo group. Among patients with 6MWT stability, tafamidis resulted in a 65% hazard reduction for ACM vs. placebo (hazard ratio 0.347 [95% CI 0.166-0.724]; p = 0.0048). Model-adjusted annual CVH rates with tafamidis were numerically lower vs. placebo (6MWT stability: 0.65 vs. 0.96; 6MWT progression: 1.19 vs. 1.59). A 32% reduction in CVH risk was observed with tafamidis vs. placebo (risk ratio 0.677 [0.500-0.916]; p = 0.0115) with 6MWT stability.</p><p><strong>Conclusions: </strong>Tafamidis resulted in a larger proportion of patients with functional stability after 12 months of treatment, with a significantly lower risk of ACM and CVH in patients with 6MWT stability during the subsequent 18 months. This post hoc analysis suggests treatment with tafamidis plays an important role in maintaining functional stability and improving outcomes for patients with ATTR-CM. Graphical abstract available for this article.  TRIAL REGISTRATION: Clinicaltrials.gov ID NCT01994889.</p>","PeriodicalId":9561,"journal":{"name":"Cardiology and Therapy","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148838975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiovascular-Related Mortality and Hospitalizations in Patients with Transthyretin Amyloid Cardiomyopathy Treated with Tafamidis: A Post Hoc Analysis of the Phase 3 ATTR-ACT and Long-Term Extension.","authors":"Thibaud Damy, Ronald Witteles, Francesco Cappelli, Ronnie Wang, Martha Grogan","doi":"10.1007/s40119-026-00470-8","DOIUrl":"https://doi.org/10.1007/s40119-026-00470-8","url":null,"abstract":"<p><strong>Introduction: </strong>Patients with transthyretin amyloid cardiomyopathy (ATTR-CM) are at high risk of cardiovascular (CV)-related hospitalizations (CVH), which are associated with higher mortality. In the phase 3 study ATTR-ACT, treatment with tafamidis significantly reduced CVH versus placebo.</p><p><strong>Methods: </strong>This post hoc analysis included patients from ATTR-ACT (30 months) and its long-term extension (LTE; 60 months) receiving tafamidis 80 mg (n = 176) or placebo in ATTR-ACT and switched to tafamidis 80 mg in the LTE (n = 177). CV-related events (CV-related mortality [CVM] and/or recurrent CVH) and CVM were evaluated. Liu-Wei-Yang-Ying and Cox proportional hazard models were used to evaluate time to recurrent CV-related events and CVM, respectively.</p><p><strong>Results: </strong>During ATTR-ACT, cumulative incidence of first and recurrent CV-related events in the tafamidis group was lower versus placebo from month 9 and incidence of CVM was lower from month 18. These trends continued throughout the LTE. At month 24, a significant 29% hazard reduction was observed for CV-related events with tafamidis 80 mg versus placebo (incidence 48% vs 61%; hazard ratio [HR] 0.713 [95% CI 0.524-0.970]; p = 0.0310). Hazard reduction remained significant until month 90 with continuous tafamidis 80 mg and was 37% at month 90 (incidence 77% vs 79%; HR 0.629 [95% CI 0.491-0.806; p = 0.0002]). Incidence of CVM with continuous tafamidis 80 mg was lower versus placebo(/tafamidis 80 mg) at month 24 (21% vs 29%) and month 90 (39% vs 47%), with significant hazard reductions of 38% (HR 0.618 [95% CI 0.401-0.954]; p = 0.0299) and 39% (HR 0.607 [95% CI 0.436-0.843]; p = 0.0029), respectively. Similar trends were observed in patients with baseline New York Heart Association (NYHA) functional class I/II but not with baseline NYHA class III.</p><p><strong>Conclusion: </strong>Treatment with tafamidis significantly reduced the risk of CV-related events, including recurrent CVH and CVM, as early as month 24. This benefit continued for ≤ 90 months. Graphical abstract available for this article.</p><p><strong>Trial registry: </strong>ClinicalTrial.gov identifiers: NCT01994889; NCT02791230.</p>","PeriodicalId":9561,"journal":{"name":"Cardiology and Therapy","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148839007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}