Pub Date : 2024-10-15DOI: 10.1016/j.ahj.2024.10.005
Nina Nouhravesh MD , Josephine Harrington MD , Laura H. Aberle BSPH , Cynthia L. Green PhD , Kathleen Voss , Dave Holdsworth , Kurt Misialek , Bartel T. Slaugh PhD , Mandee Wieand MS, CFS , William S. Yancy Jr MD , Neha Pagidipati MD, MPH , Robert J. Mentz MD
Background
Given the increasing interest in dietary interventions to improve cardiovascular health, this trial assessed the impact of fortified eggs (FE) versus nonegg supplemented diet and time-restricted eating (TRE) versus usual care diet on cardiovascular biomarkers.
Methods
The study was a unblinded, 2-by-2 factorial design, which randomized patients, with either a prior cardiovascular event or 2 cardiovascular risk factors, to FE or a nonegg supplemented diet and TRE or usual care diet. Patients randomized to FE were instructed to consume at least 12 FE/week (with eggs provided); those on a nonegg supplemented diet restricted egg consumption to <2 eggs/week. TRE participants were instructed to consume all calories within an 8-hour window daily and fasted for the remaining 16 hours. Patients randomized to usual diet were advised to maintain current dietary habits. Follow-up was performed in-person at 1 and 4 months, and telephone calls at 2 and 3 months. Co-primary endpoints were 4-month LDL- and HDL-cholesterol. Secondary endpoints included additional lipids, cardiometabolic- and inflammatory biomarkers and micronutrient levels at 4-months.
Results
Overall, 140 patients were randomized with median (25th, 75th percentiles) age 66 (58, 73) years; 72 (51%) women, 38 (27%) Black, and 33 (24%) with diabetes mellitus. The difference in least squares (LS) means from baseline to 4-months for HDL and LDL levels revealed no significant clinical difference between FE vs nonegg supplemented diet (HDL: -0.64 mg/dL [95% CI: -3.86, 2.58]; LDL: -3.14 mg/dL [-10.81, 4.52]) and TRE vs usual care diet (HDL: 1.51 mg/dL [-1.65, 4.68]; LDL 1.17 mg/dL [-6.36, 8.70]). Prespecified subgroups revealed a nonsignificant HDL increase and LDL decrease with FE in patients ≥65 years.
Conclusions
These data did not demonstrate clinically relevant differences in changes in LDL and HDL levels over 4 months with FE and TRE compared with nonegg supplemented diet and usual care diet, respectively, providing evidence that adverse short-term lipid and biomarker changes did not occur with FE consumption.
Trial Registration
ClinicalTrials.gov Identifier: NCT04673721.
背景：鉴于人们对改善心血管健康的饮食干预越来越感兴趣，本试验评估了强化鸡蛋（FE）与非鸡蛋补充饮食、限时进食（TRE）与常规饮食对心血管生物标志物的影响：该研究采用非盲法、2乘2因子设计，将曾发生过心血管事件或具有两种心血管风险因素的患者随机分配到添加鸡蛋或不添加鸡蛋的饮食中，以及限时进食或常规饮食中。随机摄入 FE 的患者被要求每周至少摄入 12 FE（提供鸡蛋）；摄入非鸡蛋补充饮食的患者则限制鸡蛋摄入量：共有 140 名患者接受了随机治疗，中位数（第 25 个百分位数，第 75 个百分位数）年龄为 66（58，73）岁；72（51%）名女性，38（27%）名黑人，33（24%）名糖尿病患者。高密度脂蛋白和低密度脂蛋白水平从基线到 4 个月的最小二乘法（LS）均值差异显示，FE 与非鸡蛋补充饮食（高密度脂蛋白：-0.64 mg/dL [95% CI：-3.86, 2.58]；低密度脂蛋白：-3.14 mg/dL [-10.81, 4.52]）和 TRE 与常规护理饮食（高密度脂蛋白：1.51 mg/dL [-1.65, 4.68]；低密度脂蛋白 1.17 mg/dL [-6.36, 8.70]）之间没有显著的临床差异。预先指定的亚组显示，在≥65 岁的患者中，高密度脂蛋白随 FE 的增加而增加，低密度脂蛋白随 FE 的减少而减少，但不显著：这些数据表明，与不补充鸡蛋的饮食和常规护理饮食相比，食用 FE 和 TRE 4 个月后低密度脂蛋白和高密度脂蛋白水平的变化没有临床相关性差异，提供了食用 FE 不会导致短期血脂和生物标志物发生不良变化的证据：试验注册：ClinicalTrials.gov Identifier：试验注册：ClinicalTrials.gov Identifier：NCT04673721。
{"title":"Effects of fortified eggs and time-restricted eating on cardiometabolic health: The prosperity trial","authors":"Nina Nouhravesh MD , Josephine Harrington MD , Laura H. Aberle BSPH , Cynthia L. Green PhD , Kathleen Voss , Dave Holdsworth , Kurt Misialek , Bartel T. Slaugh PhD , Mandee Wieand MS, CFS , William S. Yancy Jr MD , Neha Pagidipati MD, MPH , Robert J. Mentz MD","doi":"10.1016/j.ahj.2024.10.005","DOIUrl":"10.1016/j.ahj.2024.10.005","url":null,"abstract":"<div><h3>Background</h3><div>Given the increasing interest in dietary interventions to improve cardiovascular health, this trial assessed the impact of fortified eggs (FE) versus nonegg supplemented diet and time-restricted eating (TRE) versus usual care diet on cardiovascular biomarkers.</div></div><div><h3>Methods</h3><div>The study was a unblinded, 2-by-2 factorial design, which randomized patients, with either a prior cardiovascular event or 2 cardiovascular risk factors, to FE or a nonegg supplemented diet <em>and</em> TRE or usual care diet. Patients randomized to FE were instructed to consume at least 12 FE/week (with eggs provided); those on a nonegg supplemented diet restricted egg consumption to <2 eggs/week. TRE participants were instructed to consume all calories within an 8-hour window daily and fasted for the remaining 16 hours. Patients randomized to usual diet were advised to maintain current dietary habits. Follow-up was performed in-person at 1 and 4 months, and telephone calls at 2 and 3 months. Co-primary endpoints were 4-month LDL- and HDL-cholesterol. Secondary endpoints included additional lipids, cardiometabolic- and inflammatory biomarkers and micronutrient levels at 4-months.</div></div><div><h3>Results</h3><div>Overall, 140 patients were randomized with median (25th, 75th percentiles) age 66 (58, 73) years; 72 (51%) women, 38 (27%) Black, and 33 (24%) with diabetes mellitus. The difference in least squares (LS) means from baseline to 4-months for HDL and LDL levels revealed no significant clinical difference between FE vs nonegg supplemented diet (HDL: -0.64 mg/dL [95% CI: -3.86, 2.58]; LDL: -3.14 mg/dL [-10.81, 4.52]) and TRE vs usual care diet (HDL: 1.51 mg/dL [-1.65, 4.68]; LDL 1.17 mg/dL [-6.36, 8.70]). Prespecified subgroups revealed a nonsignificant HDL increase and LDL decrease with FE in patients ≥65 years.</div></div><div><h3>Conclusions</h3><div>These data did not demonstrate clinically relevant differences in changes in LDL and HDL levels over 4 months with FE and TRE compared with nonegg supplemented diet and usual care diet, respectively, providing evidence that adverse short-term lipid and biomarker changes did not occur with FE consumption.</div></div><div><h3>Trial Registration</h3><div>ClinicalTrials.gov Identifier: NCT04673721.</div></div>","PeriodicalId":7868,"journal":{"name":"American heart journal","volume":"279 ","pages":"Pages 27-39"},"PeriodicalIF":3.7,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142456288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-11DOI: 10.1016/j.ahj.2024.10.003
Shujie Yan MD, PhD , Fuqing Jiang MD , Yanhua Sun MD , Yang Wang PhD , Jianxi Ye MD, PhD , Jianchao Li MD , Hui Yang MD , Shifu Wang MD , Yi Song MD , Chengbin Zhou MD, PhD , Bingyang Ji MD, PhD
Background
The mortality and morbidity of emergency total aortic arch replacement (TAAR) for acute type A aortic dissection (ATAAD) is high, which is partly due to the excessively activated systemic inflammatory response. Methylprednisolone, an anti-inflammatory agent, might suppress the systemic inflammatory response and lead to improved outcomes. However, the protective effects of methylprednisolone on TAAR for ATAAD were not clarified. The usage and dosage varied in different centers across the world.
Methods and results
The Medal trial is a prospective, multicenter, randomized, double-blind, placebo-controlled, parallel-group trial to evaluate whether 500 mg methylprednisolone IV before cardiopulmonary bypass could reduce the incidence of postoperative major organ injury, compared to placebo. Adult patients with the diagnosis with ATAAD, awaiting emergency total aortic arch replacement with hypothermic circulatory arrest and selective cerebral perfusion will be included in the trial. A total of 340 eligible subjects from 9 large cardiovascular centers will be randomized in a 1:1 ratio to receive 500 mg methylprednislone or placebo before cardiopulmonary bypass. The primary outcome is postoperative major adverse outcome [defined as all-cause death or postoperative neurological deficit or KDIGO II -III acute kidney injury or respiratory syndrome (tracheal intubation> 72 hours, tracheostomy or re-intubation) until postoperative day 30 or patient discharge]. The study has received approval from the local Ethics Committees of the 9 participating centers, and enrolled its first subject in June 24, 2022. As of September 5, 2024, 323 subjects have been enrolled. Results of the Medal trial will be published once data collection and analysis have been completed.
Conclusions
The Medal trial will determine the effectiveness of 500 mg methylprednisolone on the outcomes of patients with ATAAD undergoing TAAR.
{"title":"Methylprednisolone for acute type A aortic dissection patients undergoing total arch replacement: Design and rationale of the Medal trial","authors":"Shujie Yan MD, PhD , Fuqing Jiang MD , Yanhua Sun MD , Yang Wang PhD , Jianxi Ye MD, PhD , Jianchao Li MD , Hui Yang MD , Shifu Wang MD , Yi Song MD , Chengbin Zhou MD, PhD , Bingyang Ji MD, PhD","doi":"10.1016/j.ahj.2024.10.003","DOIUrl":"10.1016/j.ahj.2024.10.003","url":null,"abstract":"<div><h3>Background</h3><div>The mortality and morbidity of emergency total aortic arch replacement (TAAR) for acute type A aortic dissection (ATAAD) is high, which is partly due to the excessively activated systemic inflammatory response. Methylprednisolone, an anti-inflammatory agent, might suppress the systemic inflammatory response and lead to improved outcomes. However, the protective effects of methylprednisolone on TAAR for ATAAD were not clarified. The usage and dosage varied in different centers across the world.</div></div><div><h3>Methods and results</h3><div>The Medal trial is a prospective, multicenter, randomized, double-blind, placebo-controlled, parallel-group trial to evaluate whether 500 mg methylprednisolone IV before cardiopulmonary bypass could reduce the incidence of postoperative major organ injury, compared to placebo. Adult patients with the diagnosis with ATAAD, awaiting emergency total aortic arch replacement with hypothermic circulatory arrest and selective cerebral perfusion will be included in the trial. A total of 340 eligible subjects from 9 large cardiovascular centers will be randomized in a 1:1 ratio to receive 500 mg methylprednislone or placebo before cardiopulmonary bypass. The primary outcome is postoperative major adverse outcome [defined as all-cause death or postoperative neurological deficit or KDIGO II -III acute kidney injury or respiratory syndrome (tracheal intubation> 72 hours, tracheostomy or re-intubation) until postoperative day 30 or patient discharge]. The study has received approval from the local Ethics Committees of the 9 participating centers, and enrolled its first subject in June 24, 2022. As of September 5, 2024, 323 subjects have been enrolled. Results of the Medal trial will be published once data collection and analysis have been completed.</div></div><div><h3>Conclusions</h3><div>The Medal trial will determine the effectiveness of 500 mg methylprednisolone on the outcomes of patients with ATAAD undergoing TAAR.</div></div><div><h3>Registration</h3><div>URL <span><span>https://www.chictr.org.cn/searchprojEN.html</span><svg><path></path></svg></span> (Chinese Clinical Trial Registry). Unique identifier: ChiCTR2200059286</div></div>","PeriodicalId":7868,"journal":{"name":"American heart journal","volume":"279 ","pages":"Pages 20-26"},"PeriodicalIF":3.7,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142456290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-10DOI: 10.1016/j.ahj.2024.10.006
Richard P Whitlock, Patrick M McCarthy, Marc W Gerdisch, Basel Ramlawi, John H Alexander, David Z Rose, Jeffrey S Healey, Yashasvi Awasthi Sharma, Emilie P Belley-Côté, Stuart J Connolly
Introduction: Left atrial appendage exclusion (LAAE) has been shown in randomized trials to reduce ischemic stroke risk in patients undergoing cardiac surgery with known atrial fibrillation (AF). Many patients undergoing cardiac surgery without pre-existing AF are at risk of stroke and may benefit from LAAE.
Methods: Left Atrial Appendage Exclusion for Prophylactic Stroke Reduction (LeAAPS) is an international, prospective, randomized, multicenter, blinded trial evaluating the effectiveness of LAAE in preventing ischemic stroke or systemic embolism in patients undergoing cardiac surgery at increased risk of AF and ischemic stroke. The trial will enroll 6500 patients at increased risk of stroke in whom a cardiac surgery is planned at 250 sites worldwide. Eligible patients are ≥18 years old, have no pre-existing AF but are at increased risk for AF and stroke (based on age, CHA2DS2-VASc score, left atrium size or brain natriuretic peptide). Patients are randomized 1:1 to receive either LAAE with AtriClip or no LAAE during cardiac surgery. Healthcare providers outside of the operating room and the patient will be blinded to allocation. The primary effectiveness endpoint is the first occurrence of ischemic stroke, systemic arterial embolism, or surgical or endovascular LAA closure. The powered secondary effectiveness endpoint is ischemic stroke or systemic arterial embolism. The primary safety endpoint is the occurrence of one of the following events (through 30 days): pericardial effusion requiring percutaneous or surgical treatment, peri-operative major bleeding, deep sternal wound infection, or myocardial infarction. Other endpoints include mortality, rehospitalizations, clinically diagnosed AF, transient ischemic attack, and cognitive and quality of life assessments. Follow-up is every 6 months for a minimum of 5 years; primary analysis occurs when 469 patients have had an ischemic stroke or systemic embolism.
Conclusion: The results of the LeAAPS trial will demonstrate whether LAAE with AtriClip at the time of other routine cardiac surgery reduces stroke or systemic arterial embolism during long-term follow-up in patients at high risk of stroke without pre-existing AF.
{"title":"The left atrial appendage exclusion for prophylactic stroke reduction (leaaps) trial: rationale and design.","authors":"Richard P Whitlock, Patrick M McCarthy, Marc W Gerdisch, Basel Ramlawi, John H Alexander, David Z Rose, Jeffrey S Healey, Yashasvi Awasthi Sharma, Emilie P Belley-Côté, Stuart J Connolly","doi":"10.1016/j.ahj.2024.10.006","DOIUrl":"https://doi.org/10.1016/j.ahj.2024.10.006","url":null,"abstract":"<p><strong>Introduction: </strong>Left atrial appendage exclusion (LAAE) has been shown in randomized trials to reduce ischemic stroke risk in patients undergoing cardiac surgery with known atrial fibrillation (AF). Many patients undergoing cardiac surgery without pre-existing AF are at risk of stroke and may benefit from LAAE.</p><p><strong>Methods: </strong>Left Atrial Appendage Exclusion for Prophylactic Stroke Reduction (LeAAPS) is an international, prospective, randomized, multicenter, blinded trial evaluating the effectiveness of LAAE in preventing ischemic stroke or systemic embolism in patients undergoing cardiac surgery at increased risk of AF and ischemic stroke. The trial will enroll 6500 patients at increased risk of stroke in whom a cardiac surgery is planned at 250 sites worldwide. Eligible patients are ≥18 years old, have no pre-existing AF but are at increased risk for AF and stroke (based on age, CHA<sub>2</sub>DS<sub>2</sub>-VASc score, left atrium size or brain natriuretic peptide). Patients are randomized 1:1 to receive either LAAE with AtriClip or no LAAE during cardiac surgery. Healthcare providers outside of the operating room and the patient will be blinded to allocation. The primary effectiveness endpoint is the first occurrence of ischemic stroke, systemic arterial embolism, or surgical or endovascular LAA closure. The powered secondary effectiveness endpoint is ischemic stroke or systemic arterial embolism. The primary safety endpoint is the occurrence of one of the following events (through 30 days): pericardial effusion requiring percutaneous or surgical treatment, peri-operative major bleeding, deep sternal wound infection, or myocardial infarction. Other endpoints include mortality, rehospitalizations, clinically diagnosed AF, transient ischemic attack, and cognitive and quality of life assessments. Follow-up is every 6 months for a minimum of 5 years; primary analysis occurs when 469 patients have had an ischemic stroke or systemic embolism.</p><p><strong>Conclusion: </strong>The results of the LeAAPS trial will demonstrate whether LAAE with AtriClip at the time of other routine cardiac surgery reduces stroke or systemic arterial embolism during long-term follow-up in patients at high risk of stroke without pre-existing AF.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov, Identifier: NCT05478304, https://clinicaltrials.gov/study/NCT05478304?term=%20NCT05478304&rank=1.</p>","PeriodicalId":7868,"journal":{"name":"American heart journal","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142456292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-05DOI: 10.1016/j.ahj.2024.10.002
Jani Thuraiaiyah , Troels Højsgaard Jørgensen , Jesper Møller Jensen , Andreas Fuchs , Yannick Willemen , Christian Juhl Terkelsen , Klaus Fuglsang Kofoed , Lars Søndergaard , Bjarne Linde Nørgaard , Ole De Backer
Background
Transcatheter aortic valve replacement (TAVR) has become the standard-of-care treatment for a majority of patients with severe, symptomatic aortic stenosis. The postprocedural antithrombotic therapeutic management is still a topic of debate and could affect the incidence of HALT, a phenomenon which can be assessed by 4-dimensional computed tomography (4DCT).
Trial design
The NOTION-4 trial is a randomized controlled trial comprising TAVR patients with no indication for oral anticoagulant (OAC) therapy, comparing lifelong single antiplatelet therapy (standard arm) versus early 3-month direct oral anticoagulant (DOAC) therapy followed by single antiplateletet therapy (experimental arm). The incidence of HALT and clinical endpoints will be evaluated in both groups at 3 months, 1 year and 5 years after randomization. The primary endpoint is the number of patients with at least 1 bioprosthetic aortic valve leaflet with HALT as assessed by cardiac 4DCT imaging at 1 year. The trial is powered for superiority testing and started enrollment in 2021. In total, 324 patients will be included. The last patient is expected to be enrolled by the end of 2024 and the primary endpoint is to be presented in 2026.
Conclusion and perspective
The NOTION-4 trial aims to study whether an early 3-month DOAC therapy after TAVR can result in a sustained lower incidence of HALT in transcatheter aortic valves. This trial holds the potential to give valuable insights into whether early OAC therapy should be integrated in future guidelines for post-TAVR antithrombotic therapeutic management.
Trial registration
NOTION-4, ClinicalTrials.gov ID NCT06449469, https://clinicaltrials.gov/study/NCT06449469
背景：经导管主动脉瓣置换术（TAVR）已成为大多数严重无症状主动脉瓣狭窄患者的标准治疗方法。经导管主动脉瓣置换术（TAVR）已成为大多数重度无症状主动脉瓣狭窄患者的标准治疗方法，但术后抗血栓治疗管理仍是一个争论不休的话题，它可能会影响 HALT 的发生率，而 HALT 可通过四维计算机断层扫描（4DCT）进行评估：NOTION-4试验是一项随机对照试验，包括无口服抗凝剂（OAC）治疗指征的TAVR患者，比较终生单一抗血小板治疗（标准组）与早期3个月直接口服抗凝剂（DOAC）治疗后单一抗血小板治疗（实验组）。将在随机分组后的 3 个月、1 年和 5 年对两组的 HALT 发生率和临床终点进行评估。主要终点是通过心脏 4DCT 成像评估 1 年后至少有一片生物人工主动脉瓣叶出现 HALT 的患者人数。该试验已通过优效性测试，并于2021年开始招募患者。总共将纳入 324 名患者。最后一名患者预计将于2024年底入组，主要终点将于2026年公布：NOTION-4 试验旨在研究 TAVR 术后早期 3 个月 DOAC 治疗能否持续降低经导管主动脉瓣的 HALT 发生率。该试验有可能为是否应将早期OAC治疗纳入未来TAVR术后抗血栓治疗指南提供有价值的见解：NOTION-4，ClinicalTrials.gov ID NCT06449469，https://clinicaltrials.gov/study/NCT06449469。
{"title":"Prospective study on the impact of different antithrombotic therapies on subclinical leaflet thickening and its temporal dynamics in transcatheter aortic valves—The NOTION-4 trial","authors":"Jani Thuraiaiyah , Troels Højsgaard Jørgensen , Jesper Møller Jensen , Andreas Fuchs , Yannick Willemen , Christian Juhl Terkelsen , Klaus Fuglsang Kofoed , Lars Søndergaard , Bjarne Linde Nørgaard , Ole De Backer","doi":"10.1016/j.ahj.2024.10.002","DOIUrl":"10.1016/j.ahj.2024.10.002","url":null,"abstract":"<div><h3>Background</h3><div>Transcatheter aortic valve replacement (TAVR) has become the standard-of-care treatment for a majority of patients with severe, symptomatic aortic stenosis. The postprocedural antithrombotic therapeutic management is still a topic of debate and could affect the incidence of HALT, a phenomenon which can be assessed by 4-dimensional computed tomography (4DCT).</div></div><div><h3>Trial design</h3><div>The NOTION-4 trial is a randomized controlled trial comprising TAVR patients with no indication for oral anticoagulant (OAC) therapy, comparing lifelong single antiplatelet therapy (standard arm) versus early 3-month direct oral anticoagulant (DOAC) therapy followed by single antiplateletet therapy (experimental arm). The incidence of HALT and clinical endpoints will be evaluated in both groups at 3 months, 1 year and 5 years after randomization. The primary endpoint is the number of patients with at least 1 bioprosthetic aortic valve leaflet with HALT as assessed by cardiac 4DCT imaging at 1 year. The trial is powered for superiority testing and started enrollment in 2021. In total, 324 patients will be included. The last patient is expected to be enrolled by the end of 2024 and the primary endpoint is to be presented in 2026.</div></div><div><h3>Conclusion and perspective</h3><div>The NOTION-4 trial aims to study whether an early 3-month DOAC therapy after TAVR can result in a sustained lower incidence of HALT in transcatheter aortic valves. This trial holds the potential to give valuable insights into whether early OAC therapy should be integrated in future guidelines for post-TAVR antithrombotic therapeutic management.</div></div><div><h3>Trial registration</h3><div>NOTION-4, ClinicalTrials.gov ID NCT06449469, <span><span>https://clinicaltrials.gov/study/NCT06449469</span><svg><path></path></svg></span></div></div>","PeriodicalId":7868,"journal":{"name":"American heart journal","volume":"279 ","pages":"Pages 1-8"},"PeriodicalIF":3.7,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142387385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
It is uncertain whether the efficacy and safety of dual antiplatelet therapy (DAPT) in patients with high bleeding risk (HBR) vary according to DAPT duration and stent type (eg, durable polymer drug-eluting stents (DP-DESs), biodegradable polymer DESs (BP-DESs), or polymer-free drug-coated stents (PF-DCSs)). We aimed to study the stent type and DAPT duration appropriate for patients with HBR.
Methods
PubMed and EMBASE were searched until October 2023. Randomized controlled trials (RCTs) involving patients with HBR that compared standard DAPT (6-12 months) with DP- or BP-DES versus short DAPT (≤3 months) with DP- or BP-DES or PF-DCS or bare-metal stent (BMS) were identified. The primary efficacy outcome was major adverse cardiovascular events (MACEs), defined as cardiovascular death, myocardial infarction (MI), and stroke. The primary safety outcome was major bleeding. Secondary outcomes included MI and stent thrombosis (ST). We performed a network meta-analysis using a random effects model.
Results
Thirteen RCTs with a total of 19,418 patients with HBR were included. Compared to standard DAPT with DP-DES, short DAPT with BMS was associated with a higher risk of MACE and MI. For major bleeding, short DAPT strategies were associated with a lower risk than standard DAPT strategies (e.g. short DAPT with DP-DES vs standard DAPT with DP-DES; HR[95% CI]: 0.48[0.28-0.82]). Interestingly, the use of BP-DES was associated with a higher risk of ST than DP-DES (e.g. standard DAPT with BP-DES vs short DAPT with DP-DES; HR[95% CI]: 2.65[1.03-6.79]).
Conclusions
In patients with HBR who underwent percutaneous coronary intervention, a short DAPT strategy with DP-DES should be used since it offers the best combination of efficacy and safety.
{"title":"Dual antiplatelet therapy duration and stent type in patients with high bleeding risk: A systematic review and network meta-analysis","authors":"Tetsuya Saito MD , Toshiki Kuno MD, PhD , Tomohiro Fujisaki MD , Rahul Gupta MD , Kaveh Hosseini MD-MPH , Hisato Takagi MD, PhD , Jose Wiley MD, MPH , Sripal Bangalore MD, MHA","doi":"10.1016/j.ahj.2024.10.004","DOIUrl":"10.1016/j.ahj.2024.10.004","url":null,"abstract":"<div><h3>Background</h3><div>It is uncertain whether the efficacy and safety of dual antiplatelet therapy (DAPT) in patients with high bleeding risk (HBR) vary according to DAPT duration and stent type (eg, durable polymer drug-eluting stents (DP-DESs), biodegradable polymer DESs (BP-DESs), or polymer-free drug-coated stents (PF-DCSs)). We aimed to study the stent type and DAPT duration appropriate for patients with HBR.</div></div><div><h3>Methods</h3><div>PubMed and EMBASE were searched until October 2023. Randomized controlled trials (RCTs) involving patients with HBR that compared standard DAPT (6-12 months) with DP- or BP-DES versus short DAPT (≤3 months) with DP- or BP-DES or PF-DCS or bare-metal stent (BMS) were identified. The primary efficacy outcome was major adverse cardiovascular events (MACEs), defined as cardiovascular death, myocardial infarction (MI), and stroke. The primary safety outcome was major bleeding. Secondary outcomes included MI and stent thrombosis (ST). We performed a network meta-analysis using a random effects model.</div></div><div><h3>Results</h3><div>Thirteen RCTs with a total of 19,418 patients with HBR were included. Compared to standard DAPT with DP-DES, short DAPT with BMS was associated with a higher risk of MACE and MI. For major bleeding, short DAPT strategies were associated with a lower risk than standard DAPT strategies (e.g. short DAPT with DP-DES vs standard DAPT with DP-DES; HR[95% CI]: 0.48[0.28-0.82]). Interestingly, the use of BP-DES was associated with a higher risk of ST than DP-DES (e.g. standard DAPT with BP-DES vs short DAPT with DP-DES; HR[95% CI]: 2.65[1.03-6.79]).</div></div><div><h3>Conclusions</h3><div>In patients with HBR who underwent percutaneous coronary intervention, a short DAPT strategy with DP-DES should be used since it offers the best combination of efficacy and safety.</div></div>","PeriodicalId":7868,"journal":{"name":"American heart journal","volume":"279 ","pages":"Pages 9-19"},"PeriodicalIF":3.7,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142387384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-27DOI: 10.1016/j.ahj.2024.09.029
K.G. Volpp MD, PhD , K. Mahraj MSI , L.A. Norton MA, MBE , D.A. Asch MD, MBA , K. Glanz PhD, MPH , S.J. Mehta MD, MBA , M. Balasta MD , W. Kellum MD , J. Wood MD , L.B. Russell PhD , A.C. Fanaroff MD , S. Bakshi MD , D. Jacoby MD , J.B. Cohen MD, MSCE , M.J. Press MD , K. Clark MPH , J. Zhu MS, MBA , C. Rareside MS , L.E. Ashcraft PhD , C. Snider MPH , M.E. Putt PhD
Rationales
Atherosclerotic Cardiovascular Disease (ASCVD) is the leading cause of morbidity and mortality in the United States. Suboptimal control of hypertension and hyperlipidemia are common factors contributing to ASCVD risk. The Penn Medicine Healthy Heart (PMHH) Study is a randomized clinical trial testing the effectiveness of a system designed to offload work from primary care clinicians and improve patient follow-through with risk reduction strategies by using a centralized team of nonclinical navigators and advanced practice providers, remote monitoring, and bi-directional text messaging, augmented by behavioral science engagement strategies. The intervention builds on prior nonrandomized evaluations of these design elements that demonstrated significant improvement in patients’ systolic blood pressure and LDL Cholesterol (LDL-C).
Primary Hypothesis
Penn Medicine Healthy Heart will significantly improve systolic blood pressure and LDL-C compared to usual care over the 6 months of this intervention.
Design
Randomized clinical trial of Penn Medicine Healthy Heart in patients aged 35-80 years at elevated risk of ASCVD whose systolic blood pressure and LDL-C are not well controlled. The intervention consists of 4 modules that address blood pressure management, lipid management, nutrition, and smoking cessation, offered in a phased approach to give the participant time to learn about each topic, adopt any recommendations, and build a relationship with the care team.
Sites
University of Pennsylvania Health System at primary care practices located in inner-city urban and rural/semi-rural areas.
Primary Outcomes
Improvement in systolic blood pressure and LDL-C.
Secondary Outcomes
Cost-effectiveness analyses are planned to evaluate the health care costs and health outcomes of the intervention approach. An implementation evaluation is planned to understand factors influencing success of the intervention.
Estimated Enrollment
2,420 active patients of Penn Medicine primary care practices who have clinical ASCVD, or who are at elevated risk for ASCVD, and who are (a) not on statins or have LDL-C >100 despite being on statins and (b) had systolic blood pressure >140 at 2 recent ambulatory visits.
Enrollment Dates
March 2024-March 2025. The intervention will last 6 months with a 12-month follow-up to determine whether its effects persist.
{"title":"Design and rationale of penn medicine healthy heart, a randomized trial of effectiveness of a centrally organized approach to blood pressure and cholesterol improvement among patients at elevated risk of atherosclerotic cardiovascular disease","authors":"K.G. Volpp MD, PhD , K. Mahraj MSI , L.A. Norton MA, MBE , D.A. Asch MD, MBA , K. Glanz PhD, MPH , S.J. Mehta MD, MBA , M. Balasta MD , W. Kellum MD , J. Wood MD , L.B. Russell PhD , A.C. Fanaroff MD , S. Bakshi MD , D. Jacoby MD , J.B. Cohen MD, MSCE , M.J. Press MD , K. Clark MPH , J. Zhu MS, MBA , C. Rareside MS , L.E. Ashcraft PhD , C. Snider MPH , M.E. Putt PhD","doi":"10.1016/j.ahj.2024.09.029","DOIUrl":"10.1016/j.ahj.2024.09.029","url":null,"abstract":"<div><h3>Rationales</h3><div>Atherosclerotic Cardiovascular Disease (ASCVD) is the leading cause of morbidity and mortality in the United States. Suboptimal control of hypertension and hyperlipidemia are common factors contributing to ASCVD risk. The Penn Medicine Healthy Heart (PMHH) Study is a randomized clinical trial testing the effectiveness of a system designed to offload work from primary care clinicians and improve patient follow-through with risk reduction strategies by using a centralized team of nonclinical navigators and advanced practice providers, remote monitoring, and bi-directional text messaging, augmented by behavioral science engagement strategies. The intervention builds on prior nonrandomized evaluations of these design elements that demonstrated significant improvement in patients’ systolic blood pressure and LDL Cholesterol (LDL-C).</div></div><div><h3>Primary Hypothesis</h3><div>Penn Medicine Healthy Heart will significantly improve systolic blood pressure and LDL-C compared to usual care over the 6 months of this intervention.</div></div><div><h3>Design</h3><div>Randomized clinical trial of Penn Medicine Healthy Heart in patients aged 35-80 years at elevated risk of ASCVD whose systolic blood pressure and LDL-C are not well controlled. The intervention consists of 4 modules that address blood pressure management, lipid management, nutrition, and smoking cessation, offered in a phased approach to give the participant time to learn about each topic, adopt any recommendations, and build a relationship with the care team.</div></div><div><h3>Sites</h3><div>University of Pennsylvania Health System at primary care practices located in inner-city urban and rural/semi-rural areas.</div></div><div><h3>Primary Outcomes</h3><div>Improvement in systolic blood pressure and LDL-C.</div></div><div><h3>Secondary Outcomes</h3><div>Cost-effectiveness analyses are planned to evaluate the health care costs and health outcomes of the intervention approach. An implementation evaluation is planned to understand factors influencing success of the intervention.</div></div><div><h3>Estimated Enrollment</h3><div>2,420 active patients of Penn Medicine primary care practices who have clinical ASCVD, or who are at elevated risk for ASCVD, and who are (a) not on statins or have LDL-C >100 despite being on statins and (b) had systolic blood pressure >140 at 2 recent ambulatory visits.</div></div><div><h3>Enrollment Dates</h3><div>March 2024-March 2025. The intervention will last 6 months with a 12-month follow-up to determine whether its effects persist.</div></div><div><h3>Current Status</h3><div>Enrolling (1,240 enrolled as of August 15, 2024)</div></div><div><h3>Clinical Trial Registration</h3><div>NCT06062394</div></div>","PeriodicalId":7868,"journal":{"name":"American heart journal","volume":"278 ","pages":"Pages 208-222"},"PeriodicalIF":3.7,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142339529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-24DOI: 10.1016/j.ahj.2024.09.008
Chelsea Hall MD , Anna Shishkina MD , Robin Thurman FRANZCOG , Rizwana Ashraf MD , Ankita Pal MD , Daphne Horn , Anish Keepanasseril MRCPI , Rohan D'Souza MD, PhD, FRCOG
Background
Although considerable variation in the reporting and definition of outcomes in cardio-obstetrics studies is acknowledged, the extent of this variation has not been documented. The primary objective of this systematic review was to highlight this variation and inform the development of a Core Outcome Set for studies on Cardiac disease in Pregnancy (COSCarP).
Methods
Medline, Embase, Web of Science and Cochrane Central databases were searched from 1980 to 2018 to identify all English-language publications on pregnancy and heart disease. Title/abstract screening and data extraction which included details on the study, patient population, and all reported outcomes, was performed in duplicate by 2 reviewers. As the aim of the review was to identify variation in outcome reporting, risk-of-bias assessment was not performed. The study protocol was registered on PROSPERO (CRD42016038218).
Results
The final analysis included 422 cardio-obstetric studies. Maternal mortality or survival were reported in 232/422 studies, with inconsistency in terms of cause of death (all-cause [n = 65], cardiac [n = 55] or obstetric [n = 10]) or timeframe (ranging from in-hospital mortality [n = 11] to mortality 5 years following pregnancy). In 95/232 (41%) studies, the cause and timeframe were not specified. Similar inconsistencies in reporting and definitions were noted for outcomes such as heart failure (n = 298), perinatal loss (n = 296), fetal growth (n = 221), bleeding (n = 205), arrhythmias (n = 202), preterm birth (n = 191), thromboembolism (n = 153) and hypertensive disorders (n = 122). Functioning / life-impact and adverse effects of treatment were sparingly reported in published cardio-obstetric studies.
Conclusions
This systematic review hopes to create awareness among cardio-obstetrics teams about the inconsistencies in reporting and defining outcomes which makes it difficult to compare studies and perform meta-analyses. COSCarP which is being developed through international consensus between patients and care-providers will provide cardio-obstetrics teams with a minimal set of outcomes to be reported in future cardio-obstetrics studies.
{"title":"Outcome reporting in cardio-obstetrics studies: A systematic review","authors":"Chelsea Hall MD , Anna Shishkina MD , Robin Thurman FRANZCOG , Rizwana Ashraf MD , Ankita Pal MD , Daphne Horn , Anish Keepanasseril MRCPI , Rohan D'Souza MD, PhD, FRCOG","doi":"10.1016/j.ahj.2024.09.008","DOIUrl":"10.1016/j.ahj.2024.09.008","url":null,"abstract":"<div><h3>Background</h3><div>Although considerable variation in the reporting and definition of outcomes in cardio-obstetrics studies is acknowledged, the extent of this variation has not been documented. The primary objective of this systematic review was to highlight this variation and inform the development of a Core Outcome Set for studies on Cardiac disease in Pregnancy (COSCarP).</div></div><div><h3>Methods</h3><div>Medline, Embase, Web of Science and Cochrane Central databases were searched from 1980 to 2018 to identify all English-language publications on pregnancy and heart disease. Title/abstract screening and data extraction which included details on the study, patient population, and all reported outcomes, was performed in duplicate by 2 reviewers. As the aim of the review was to identify variation in outcome reporting, risk-of-bias assessment was not performed. The study protocol was registered on PROSPERO (CRD42016038218).</div></div><div><h3>Results</h3><div>The final analysis included 422 cardio-obstetric studies. Maternal mortality or survival were reported in 232/422 studies, with inconsistency in terms of cause of death (all-cause [n = 65], cardiac [n = 55] or obstetric [n = 10]) or timeframe (ranging from in-hospital mortality [n = 11] to mortality 5 years following pregnancy). In 95/232 (41%) studies, the cause and timeframe were not specified. Similar inconsistencies in reporting and definitions were noted for outcomes such as heart failure (n = 298), perinatal loss (n = 296), fetal growth (n = 221), bleeding (n = 205), arrhythmias (n = 202), preterm birth (n = 191), thromboembolism (n = 153) and hypertensive disorders (n = 122). Functioning / life-impact and adverse effects of treatment were sparingly reported in published cardio-obstetric studies.</div></div><div><h3>Conclusions</h3><div>This systematic review hopes to create awareness among cardio-obstetrics teams about the inconsistencies in reporting and defining outcomes which makes it difficult to compare studies and perform meta-analyses. COSCarP which is being developed through international consensus between patients and care-providers will provide cardio-obstetrics teams with a minimal set of outcomes to be reported in future cardio-obstetrics studies.</div></div>","PeriodicalId":7868,"journal":{"name":"American heart journal","volume":"278 ","pages":"Pages 223-234"},"PeriodicalIF":3.7,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142339530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cognitive decline and dementia have been reportedly linked to atherosclerosis, the main cause of cardiovascular disease. Cohort studies identifying early brain alterations associated with subclinical atherosclerosis are warranted to understand the potential of prevention strategies before cerebral damage becomes symptomatic and irreversible.
Methods & design
The Progression of Early Subclinical Atherosclerosis (PESA) study is a longitudinal observational cohort study that recruited 4,184 asymptomatic middle-aged individuals (40-54 years) in 2010 in Madrid (Spain) to thoroughly characterize subclinical atherosclerosis development over time. In this framework, the PESA-Brain study has been designed to identify early structural, functional and vascular brain changes associated with midlife atherosclerosis and cardiovascular risk factors. The PESA-Brain study targets 1,000 participants at the 10-year follow-up PESA visit and consists of thorough neuropsychological testing, advanced multimodal neuroimaging, and quantification of blood-based neuropathological biomarkers.
Primary hypothesis
We hypothesize that, in middle-age, the presence of cardiovascular risk factors and a high burden of subclinical atherosclerosis will be associated with structural, functional and vascular brain alterations, greater amyloid burden and subtle cognitive impairment. We further hypothesize that the link between subclinical atherosclerosis and poor brain health in midlife will be mediated by cerebrovascular pathology and intracranial atherosclerosis.
Enrollment dates
The PESA-Brain study started in October 2020 and is estimated to be completed by December 2024.
Conclusion
This study is in a unique position to unveil novel relationships between cardiovascular and brain alterations in the health-to-disease transition, which may have important implications for interventional and therapeutic approaches.
{"title":"Subclinical atherosclerosis and brain health in midlife: Rationale and design of the PESA-Brain study","authors":"Catarina Tristão-Pereira PhD , Valentin Fuster MD, PhD , Alejandro Lopez-Jimenez MD , Alberto Fernández-Pena PhD , Aurora Semerano MD , Irene Fernandez-Nueda RT , Ines Garcia-Lunar MD, PhD , Carmen Ayuso MD, PhD , Javier Sanchez-Gonzalez PhD , Borja Ibanez MD, PhD , Juan Domingo Gispert PhD , Marta Cortes-Canteli PhD","doi":"10.1016/j.ahj.2024.09.028","DOIUrl":"10.1016/j.ahj.2024.09.028","url":null,"abstract":"<div><h3>Rationale</h3><div>Cognitive decline and dementia have been reportedly linked to atherosclerosis, the main cause of cardiovascular disease. Cohort studies identifying early brain alterations associated with subclinical atherosclerosis are warranted to understand the potential of prevention strategies before cerebral damage becomes symptomatic and irreversible.</div></div><div><h3>Methods & design</h3><div>The Progression of Early Subclinical Atherosclerosis (PESA) study is a longitudinal observational cohort study that recruited 4,184 asymptomatic middle-aged individuals (40-54 years) in 2010 in Madrid (Spain) to thoroughly characterize subclinical atherosclerosis development over time. In this framework, the PESA-Brain study has been designed to identify early structural, functional and vascular brain changes associated with midlife atherosclerosis and cardiovascular risk factors. The PESA-Brain study targets 1,000 participants at the 10-year follow-up PESA visit and consists of thorough neuropsychological testing, advanced multimodal neuroimaging, and quantification of blood-based neuropathological biomarkers.</div></div><div><h3>Primary hypothesis</h3><div>We hypothesize that, in middle-age, the presence of cardiovascular risk factors and a high burden of subclinical atherosclerosis will be associated with structural, functional and vascular brain alterations, greater amyloid burden and subtle cognitive impairment. We further hypothesize that the link between subclinical atherosclerosis and poor brain health in midlife will be mediated by cerebrovascular pathology and intracranial atherosclerosis.</div></div><div><h3>Enrollment dates</h3><div>The PESA-Brain study started in October 2020 and is estimated to be completed by December 2024.</div></div><div><h3>Conclusion</h3><div>This study is in a unique position to unveil novel relationships between cardiovascular and brain alterations in the health-to-disease transition, which may have important implications for interventional and therapeutic approaches.</div><div><em>ClinicalTrials.gov identifier:</em> NCT01410318.</div></div>","PeriodicalId":7868,"journal":{"name":"American heart journal","volume":"278 ","pages":"Pages 195-207"},"PeriodicalIF":3.7,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142339531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-21DOI: 10.1016/j.ahj.2024.09.006
Charley A. Budgeon PhD , Stefan Nidorf MD , Arend Mosterd MD , Aernoud Fiolet MD , John Eikelboom MBBS , Sean O'Halloran PhD , David Joyce MD , Astrid Schut MSc , Jan Tijssen PhD , Jan H. Cornel MD , Kevin Murray PhD , Peter Thompson MD
Background
The Low Dose Colchicine 2 (LoDoCo2) trial randomized 5,522 patients with chronic coronary disease to colchicine 0.5mg daily or placebo in a 1:1 ratio and demonstrated the cardiovascular benefits of colchicine. In the trial, which was conducted in Australia and The Netherlands, a prespecified subgroup analysis suggested a difference in magnitude of treatment effect of colchicine by region (Australia: HR 0.51; 95% CI 0.39-0.67 vs The Netherlands: HR 0.92; 95% CI 0.71-1.20). The aim of this study was to explore possible explanations for the apparent difference in magnitude of treatment effect of colchicine by region in the LoDoCo2 trial.
Methods
The analysis explored potential determinants of variations in the magnitude of effectiveness of colchicine treatment across the regions. This included investigating differences in investigational product, clinical characteristics, concurrent medical therapies and the duration of follow-up using a range of statistical techniques, including sub-group, landmark and effect modification analyses.
Results
No differences were found in the colchicine product used in each region. Despite minor differences observed in baseline clinical characteristics and concomitant therapies, the effect modifier analyses demonstrated that these factors did not explain the difference in magnitude of treatment effect of colchicine by region. Randomization in Australia began more than 2 years before The Netherlands, with shorter duration of follow-up in The Netherlands compared to Australia. In a landmark analysis, over the period when more than 90% of patients in each region had been followed, the effects of colchicine were similar (Australia hazard ratio [HR] 0.58; 95% CI 0.34-0.97 vs The Netherlands HR 0.67; 95% CI 0.47-0.96).
Conclusions
After examining several plausible explanations for the observed differences in the magnitude of treatment effect of colchicine between regions in the LoDoCo2 trial could be due to the differences in duration of follow-up but a substantial portion of the differences remain unexplained.
Clinical Trial Registration
https://www.anzctr.org.au/ACTRN12614000093684.
背景：低剂量秋水仙碱 2（LoDoCo2）试验将 5522 名慢性冠心病患者按 1:1 的比例随机分配给每日 0.5 毫克秋水仙碱或安慰剂，结果显示秋水仙碱对心血管有益。该试验在澳大利亚和荷兰进行，预设的亚组分析表明，秋水仙碱的治疗效果因地区而异（澳大利亚：HR 0.51；95% C%；荷兰：HR 0.51；95% C%）：HR 0.51; 95% CI 0.39-0.67 vs The Netherlands：HR 0.92; 95% CI 0.71-1.20）。本研究旨在探讨 LoDoCo2 试验中不同地区秋水仙碱治疗效果明显不同的可能原因：方法：分析探讨了各地区秋水仙碱治疗效果差异的潜在决定因素。这包括使用一系列统计技术，包括亚组分析、地标分析和效应修正分析，调查研究产品、临床特征、并发药物疗法和随访时间的差异：结果：各地区使用的秋水仙碱产品没有差异。尽管观察到基线临床特征和伴随疗法存在微小差异，但效应修饰分析表明，这些因素并不能解释不同地区秋水仙碱治疗效果的差异。澳大利亚的随机化开始时间比荷兰早两年多，与澳大利亚相比，荷兰的随访时间更短。在一项里程碑式的分析中，当每个地区超过 90% 的患者接受随访时，秋水仙碱的疗效相似（澳大利亚危险比 [HR] 0.58 95% CI 0.34-0.97 vs 荷兰危险比 0.67 95% CI 0.47-0.96）：LoDoCo2试验中观察到的不同地区间秋水仙碱治疗效果的差异可能是由于随访时间的差异造成的，但仍有很大一部分差异无法解释。临床试验注册：https://www.anzctr.org.au/ACTRN12614000093684。
{"title":"Exploration of the regional effects of colchicine in the LoDoCo2 trial","authors":"Charley A. Budgeon PhD , Stefan Nidorf MD , Arend Mosterd MD , Aernoud Fiolet MD , John Eikelboom MBBS , Sean O'Halloran PhD , David Joyce MD , Astrid Schut MSc , Jan Tijssen PhD , Jan H. Cornel MD , Kevin Murray PhD , Peter Thompson MD","doi":"10.1016/j.ahj.2024.09.006","DOIUrl":"10.1016/j.ahj.2024.09.006","url":null,"abstract":"<div><h3>Background</h3><div>The Low Dose Colchicine 2 (LoDoCo2) trial randomized 5,522 patients with chronic coronary disease to colchicine 0.5mg daily or placebo in a 1:1 ratio and demonstrated the cardiovascular benefits of colchicine. In the trial, which was conducted in Australia and The Netherlands, a prespecified subgroup analysis suggested a difference in magnitude of treatment effect of colchicine by region (Australia: HR 0.51; 95% CI 0.39-0.67 vs The Netherlands: HR 0.92; 95% CI 0.71-1.20). The aim of this study was to explore possible explanations for the apparent difference in magnitude of treatment effect of colchicine by region in the LoDoCo2 trial.</div></div><div><h3>Methods</h3><div>The analysis explored potential determinants of variations in the magnitude of effectiveness of colchicine treatment across the regions. This included investigating differences in investigational product, clinical characteristics, concurrent medical therapies and the duration of follow-up using a range of statistical techniques, including sub-group, landmark and effect modification analyses.</div></div><div><h3>Results</h3><div>No differences were found in the colchicine product used in each region. Despite minor differences observed in baseline clinical characteristics and concomitant therapies, the effect modifier analyses demonstrated that these factors did not explain the difference in magnitude of treatment effect of colchicine by region. Randomization in Australia began more than 2 years before The Netherlands, with shorter duration of follow-up in The Netherlands compared to Australia. In a landmark analysis, over the period when more than 90% of patients in each region had been followed, the effects of colchicine were similar (Australia hazard ratio [HR] 0.58; 95% CI 0.34-0.97 vs The Netherlands HR 0.67; 95% CI 0.47-0.96).</div></div><div><h3>Conclusions</h3><div>After examining several plausible explanations for the observed differences in the magnitude of treatment effect of colchicine between regions in the LoDoCo2 trial could be due to the differences in duration of follow-up but a substantial portion of the differences remain unexplained.</div></div><div><h3>Clinical Trial Registration</h3><div><span><span>https://www.anzctr.org.au/ACTRN12614000093684</span><svg><path></path></svg></span>.</div></div>","PeriodicalId":7868,"journal":{"name":"American heart journal","volume":"278 ","pages":"Pages 186-194"},"PeriodicalIF":3.7,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142306972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-18DOI: 10.1016/j.ahj.2024.09.004
Anran Tan MS , Sushama Kattinakere Sreedhara MBBS, MSPH , Massimiliano Russo PhD , Daniel E Singer MD , Julie C. Lauffenburger PharmD, PhD , Elyse DiCesare BA , Kueiyu Joshua Lin MD, ScD
Background
Persistence and adherence to oral anticoagulants (OACs) is crucial for its effectiveness in stroke prevention in atrial fibrillation (AF). We aimed to assess the impact of different ascertainment methods on estimated persistence rates.
Methods
We conducted a retrospective cohort study based on the Medicare claims data (01/01/2013-12/31/2019). We built an incident user cohort of OAC (apixaban, dabigatran, edoxaban, rivaroxaban, and warfarin) prescription filling. We measured OAC medication persistence and adherence using the following approaches: (1) treatment-anniversary based persistence: if there is an active prescription overlapping the 180th and 365th day with vs. without a 15-day buffer period (i.e., overlapping with 165th-195th and 350th-380th day); (2) dispensing-gap-based persistence: if there is OAC discontinuation defined as having gap between prescriptions more than a threshold (e.g., 5-60 days) and secondarily, (3) proportion of days covered (PDC) adherence: proportion of days in which patient had filled medication available over the 365-day interval.
Results
We identified 1,398,692 patients who initiated OACs during the study interval. With the treatment-anniversary based approach, only 51.2% to 65.4% of the patients persisted with the medication for either warfarin or DOACs at 180 days, and the number dropped to 43.4% to 60.7% at 1 year. Adding a 15-day buffer period increased the treatment-anniversary based persistence rates by 6.5% to 10.5%. When the allowable gap increased from 5 to 60 days, the persistence rates increased by 36.3% to 42.4% for all OACs. Apixaban users had the highest PDC (74%-75%) over the 365 days, compared to other OACs (60%-69%).
Conclusions
We found that the estimated persistence rates are sensitive to the choice of ascertainment methods. When reporting and comparing persistence findings using the claims database, definitions of OAC discontinuation must be clearly delineated.
{"title":"Assessing methods to ascertain persistence and adherence of oral anticoagulants in patients with atrial fibrillation","authors":"Anran Tan MS , Sushama Kattinakere Sreedhara MBBS, MSPH , Massimiliano Russo PhD , Daniel E Singer MD , Julie C. Lauffenburger PharmD, PhD , Elyse DiCesare BA , Kueiyu Joshua Lin MD, ScD","doi":"10.1016/j.ahj.2024.09.004","DOIUrl":"10.1016/j.ahj.2024.09.004","url":null,"abstract":"<div><h3>Background</h3><div>Persistence and adherence to oral anticoagulants (OACs) is crucial for its effectiveness in stroke prevention in atrial fibrillation (AF). We aimed to assess the impact of different ascertainment methods on estimated persistence rates.</div></div><div><h3>Methods</h3><div>We conducted a retrospective cohort study based on the Medicare claims data (01/01/2013-12/31/2019). We built an incident user cohort of OAC (apixaban, dabigatran, edoxaban, rivaroxaban, and warfarin) prescription filling. We measured OAC medication persistence and adherence using the following approaches: (1) treatment-anniversary based persistence: if there is an active prescription overlapping the 180th and 365th day with vs. without a 15-day buffer period (i.e., overlapping with 165th-195th and 350th-380th day); (2) dispensing-gap-based persistence: if there is OAC discontinuation defined as having gap between prescriptions more than a threshold (e.g., 5-60 days) and secondarily, (3) proportion of days covered (PDC) adherence: proportion of days in which patient had filled medication available over the 365-day interval.</div></div><div><h3>Results</h3><div>We identified 1,398,692 patients who initiated OACs during the study interval. With the treatment-anniversary based approach, only 51.2% to 65.4% of the patients persisted with the medication for either warfarin or DOACs at 180 days, and the number dropped to 43.4% to 60.7% at 1 year. Adding a 15-day buffer period increased the treatment-anniversary based persistence rates by 6.5% to 10.5%. When the allowable gap increased from 5 to 60 days, the persistence rates increased by 36.3% to 42.4% for all OACs. Apixaban users had the highest PDC (74%-75%) over the 365 days, compared to other OACs (60%-69%).</div></div><div><h3>Conclusions</h3><div>We found that the estimated persistence rates are sensitive to the choice of ascertainment methods. When reporting and comparing persistence findings using the claims database, definitions of OAC discontinuation must be clearly delineated.</div></div>","PeriodicalId":7868,"journal":{"name":"American heart journal","volume":"278 ","pages":"Pages 161-169"},"PeriodicalIF":3.7,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142279376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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