Abstract：
UNASSIGNED: Is withholding anticoagulation for patients with isolated or incidental subsegmental pulmonary embolism clinically and cost-effective compared with full anticoagulation for 3 months?
UNASSIGNED: There has been an increase in the diagnosis of subsegmental pulmonary embolism since the advent of computed tomography pulmonary angiogram to investigate patients with suspected pulmonary embolism. Subsegmental pulmonary embolism is not often detectable with older nuclear medicine-based diagnostic imaging for ventilation/perfusion mismatch. The case fatality of pulmonary embolism has reduced as subsegmental pulmonary embolism diagnoses from computed tomography pulmonary angiogram have increased. There is growing equipoise about the optimal treatment for patients with subsegmental pulmonary embolism, given that full anticoagulation has significant risks of bleeding and subsegmental pulmonary embolism was not often diagnosed previously with ventilation/perfusion scanning and therefore most likely left predominantly untreated prior to the introduction of computed tomography pulmonary angiogram scanning.
UNASSIGNED: Determine whether withholding anticoagulation for isolated or incidental subsegmental pulmonary embolism (i.e. subsegmental pulmonary embolism with no coexisting deep-vein thrombosis) reduces the harms of recurrent thromboembolism and major bleeding compared with 3 months of full anticoagulation at 3, 6 and 12 months. Determine the rate of complications of anticoagulation therapy (predominantly bleeding) in patients with isolated subsegmental pulmonary embolism. Determine whether not treating isolated subsegmental pulmonary embolism is acceptable to clinicians and patients. Determine the reclassification rate of subsegmental pulmonary embolism diagnoses made by general reporting radiologists when reviewed by specialist respiratory radiologists and develop a set of rules to improve general radiologists\' diagnoses of subsegmental pulmonary embolism. Assess cost-effectiveness of not treating patients with isolated subsegmental pulmonary embolism with anticoagulation, taking a health service perspective.
UNASSIGNED: Prospective individually randomised open controlled trial with blinded end-point committee assessment for outcomes, powered for non-inferiority for recurrent venous thromboembolism and for superiority for bleeding events. An internal pilot phase is included for feasibility and acceptability of no anticoagulation. We planned to recruit 1466 patients from at least 50 acute hospital sites. Allowing for a dropout rate of 15%, this would have given us 90% power to detect a reduction in major and clinically relevant non-major bleeding from 7.3% in the anticoagulation arm to 3% in the intervention arm. We were powered to determine that a strategy of no anticoagulation was non-inferior to anticoagulation with an upper margin of a 2.3% increase in recurrent venous thromboembolism from an expected rate of 2% in those who receive full anticoagulation. We also planned to undertake a study comparing acute reporting radiologists\' diagnoses of subsegmental pulmonary embolism from all computed tomography pulmonary angiograms with specialist respiratory radiologists. This would have allowed us to determine safety in the pilot study (i.e. patients with pulmonary embolism that was in fact larger than subsegmental would have been identified) and develop guidance for subsegmental pulmonary embolism diagnosis for general radiologists. Patients with lived experience of thrombosis contributed to all aspects of the trial design and were part of the Trial Management Group.
UNASSIGNED: The STOPAPE trial was stopped prematurely due to a low recruitment rate in the wake of the COVID pandemic and prioritisation of recovery of the National Institute for Health and Care Research research portfolio. There are no outcome data available for this trial. Separate NIHR Library publications will detail the linked qualitative study examining the views of patients and clinicians around withholding anticoagulation for isolated subsegmental pulmonary embolism as well as presenting all collected data of recruited patients.
UNASSIGNED: This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number NIHR128073. A plain language summary of this research article is available on the NIHR Journals Library Website https://doi.org/10.3310/HRCW7937.
Pulmonary embolism is a potentially serious condition, whereby blood clots cause a blockage of the blood supply to the lungs. The diagnosis of pulmonary embolism is made with a scan of the lungs, by showing areas where blood cannot get through the vessels easily due to blood clots. The treatment of pulmonary embolism includes anticoagulant medication (‘blood thinners’) that is taken over months and includes warfarin, an injectable form of heparin and directly acting oral anticoagulants. These medications work by preventing new clots from forming while the body’s own mechanisms break down the clots. As the scanning technology for pulmonary embolism has become more sensitive, smaller clots are being diagnosed. However, small pulmonary embolisms may not cause any symptoms and may be found incidentally on scans performed for other reasons. In these situations, it is unclear whether treatment is required for the pulmonary embolism. These clots in smaller blood vessels away from the centre of the lungs (subsegmental pulmonary embolism) may be removed by the body’s own mechanisms for dissolving clots without needing medications. Anticoagulant medication can cause side effects in some patients such as bleeding. For the anticoagulant medication to be appropriate in these smaller pulmonary embolisms, the benefits from preventing future blood clots (pulmonary embolism and deep-vein thrombosis) would need to outweigh the potential risks from the medication side effects. The STOPAPE study aimed to answer this question by testing whether we can safely withhold anticoagulation from patients diagnosed with subsegmental pulmonary embolism. Although we aimed to enrol 1466 patients in the trial with half getting usual care of anticoagulation and half getting no anticoagulation, we could not recruit patients quickly enough to the trial and, as a result, we could not continue with the STOPAPE study. This study protocol is published to help future research teams that wish to answer this research question.
UNASSIGNED: There has been an increase in the diagnosis of subsegmental pulmonary embolism since the advent of computed tomography pulmonary angiogram to investigate patients with suspected pulmonary embolism. Subsegmental pulmonary embolism is not often detectable with older nuclear medicine-based diagnostic imaging for ventilation/perfusion mismatch. The case fatality of pulmonary embolism has reduced as subsegmental pulmonary embolism diagnoses from computed tomography pulmonary angiogram have increased. There is growing equipoise about the optimal treatment for patients with subsegmental pulmonary embolism, given that full anticoagulation has significant risks of bleeding and subsegmental pulmonary embolism was not often diagnosed previously with ventilation/perfusion scanning and therefore most likely left predominantly untreated prior to the introduction of computed tomography pulmonary angiogram scanning.
UNASSIGNED: Determine whether withholding anticoagulation for isolated or incidental subsegmental pulmonary embolism (i.e. subsegmental pulmonary embolism with no coexisting deep-vein thrombosis) reduces the harms of recurrent thromboembolism and major bleeding compared with 3 months of full anticoagulation at 3, 6 and 12 months. Determine the rate of complications of anticoagulation therapy (predominantly bleeding) in patients with isolated subsegmental pulmonary embolism. Determine whether not treating isolated subsegmental pulmonary embolism is acceptable to clinicians and patients. Determine the reclassification rate of subsegmental pulmonary embolism diagnoses made by general reporting radiologists when reviewed by specialist respiratory radiologists and develop a set of rules to improve general radiologists\' diagnoses of subsegmental pulmonary embolism. Assess cost-effectiveness of not treating patients with isolated subsegmental pulmonary embolism with anticoagulation, taking a health service perspective.
UNASSIGNED: Prospective individually randomised open controlled trial with blinded end-point committee assessment for outcomes, powered for non-inferiority for recurrent venous thromboembolism and for superiority for bleeding events. An internal pilot phase is included for feasibility and acceptability of no anticoagulation. We planned to recruit 1466 patients from at least 50 acute hospital sites. Allowing for a dropout rate of 15%, this would have given us 90% power to detect a reduction in major and clinically relevant non-major bleeding from 7.3% in the anticoagulation arm to 3% in the intervention arm. We were powered to determine that a strategy of no anticoagulation was non-inferior to anticoagulation with an upper margin of a 2.3% increase in recurrent venous thromboembolism from an expected rate of 2% in those who receive full anticoagulation. We also planned to undertake a study comparing acute reporting radiologists\' diagnoses of subsegmental pulmonary embolism from all computed tomography pulmonary angiograms with specialist respiratory radiologists. This would have allowed us to determine safety in the pilot study (i.e. patients with pulmonary embolism that was in fact larger than subsegmental would have been identified) and develop guidance for subsegmental pulmonary embolism diagnosis for general radiologists. Patients with lived experience of thrombosis contributed to all aspects of the trial design and were part of the Trial Management Group.
UNASSIGNED: The STOPAPE trial was stopped prematurely due to a low recruitment rate in the wake of the COVID pandemic and prioritisation of recovery of the National Institute for Health and Care Research research portfolio. There are no outcome data available for this trial. Separate NIHR Library publications will detail the linked qualitative study examining the views of patients and clinicians around withholding anticoagulation for isolated subsegmental pulmonary embolism as well as presenting all collected data of recruited patients.
UNASSIGNED: This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number NIHR128073. A plain language summary of this research article is available on the NIHR Journals Library Website https://doi.org/10.3310/HRCW7937.
Pulmonary embolism is a potentially serious condition, whereby blood clots cause a blockage of the blood supply to the lungs. The diagnosis of pulmonary embolism is made with a scan of the lungs, by showing areas where blood cannot get through the vessels easily due to blood clots. The treatment of pulmonary embolism includes anticoagulant medication (‘blood thinners’) that is taken over months and includes warfarin, an injectable form of heparin and directly acting oral anticoagulants. These medications work by preventing new clots from forming while the body’s own mechanisms break down the clots. As the scanning technology for pulmonary embolism has become more sensitive, smaller clots are being diagnosed. However, small pulmonary embolisms may not cause any symptoms and may be found incidentally on scans performed for other reasons. In these situations, it is unclear whether treatment is required for the pulmonary embolism. These clots in smaller blood vessels away from the centre of the lungs (subsegmental pulmonary embolism) may be removed by the body’s own mechanisms for dissolving clots without needing medications. Anticoagulant medication can cause side effects in some patients such as bleeding. For the anticoagulant medication to be appropriate in these smaller pulmonary embolisms, the benefits from preventing future blood clots (pulmonary embolism and deep-vein thrombosis) would need to outweigh the potential risks from the medication side effects. The STOPAPE study aimed to answer this question by testing whether we can safely withhold anticoagulation from patients diagnosed with subsegmental pulmonary embolism. Although we aimed to enrol 1466 patients in the trial with half getting usual care of anticoagulation and half getting no anticoagulation, we could not recruit patients quickly enough to the trial and, as a result, we could not continue with the STOPAPE study. This study protocol is published to help future research teams that wish to answer this research question.
摘要：
■与完全抗凝治疗3个月相比，孤立性或偶发性亚段肺栓塞患者的抗凝治疗在临床上是否具有成本效益？
■自从出现计算机断层扫描肺动脉造影以调查疑似肺栓塞患者以来，亚段肺栓塞的诊断有所增加。对于通气/灌注不匹配，基于较旧的核医学诊断成像通常无法检测到亚段肺栓塞。随着计算机断层扫描肺血管造影对亚段肺栓塞的诊断增加，肺栓塞的病死率降低。亚段肺栓塞患者的最佳治疗方法越来越均衡，考虑到完全抗凝有显著的出血风险,并且以前通常不会通过通气/灌注扫描诊断出亚段肺栓塞,因此很可能在引入计算机断层扫描肺血管造影扫描之前主要不治疗.
■确定与在3个月、6个月和12个月完全抗凝治疗相比，对孤立性或偶发性亚段肺栓塞（即无并发深静脉血栓形成的亚段肺栓塞）停止抗凝治疗是否能减少复发性血栓栓塞和大出血的危害。确定孤立性亚段肺栓塞患者抗凝治疗（主要是出血）的并发症发生率。确定临床医生和患者是否可以接受不治疗孤立的亚段肺栓塞。确定一般报告放射科医师诊断的亚段肺栓塞的再分类率，由专业呼吸放射科医师进行审查，并制定一套规则来提高普通放射科医师对亚段肺栓塞的诊断。评估未使用抗凝治疗孤立性亚段肺栓塞患者的成本-效果，从卫生服务的角度来看。
■采用盲法终点委员会评估结果的前瞻性个体随机开放对照试验，用于复发性静脉血栓栓塞的非劣效性和出血事件的优越性。包括内部试验阶段，以确保不抗凝的可行性和可接受性。我们计划从至少50个急症医院招募1466名患者。允许15%的辍学率，这将使我们有90%的功效检测出主要和临床相关的非大出血,从抗凝组的7.3%减少到干预组的3%.我们有能力确定不抗凝的策略不劣于抗凝，在接受完全抗凝治疗的患者中，复发性静脉血栓栓塞的上限从预期的2％增加了2.3％。我们还计划进行一项研究，将所有计算机断层扫描肺血管造影照片中急性报告放射科医师对亚段肺栓塞的诊断与专业呼吸放射科医师进行比较。这将使我们能够在试点研究中确定安全性（即肺栓塞患者实际上比亚节段要大），并为普通放射科医生制定亚节段肺栓塞诊断指南。有血栓形成经验的患者对试验设计的所有方面都有贡献，并且是试验管理组的一部分。
STOPAPE试验因COVID大流行后的低招募率和国家卫生与护理研究所研究组合的优先恢复而过早停止。该试验没有结果数据。单独的NIHR图书馆出版物将详细介绍相关的定性研究，以检查患者和临床医生对孤立的亚段肺栓塞的抗凝治疗的看法，并介绍所有收集的招募患者的数据。
■本文介绍了由美国国立卫生与护理研究所（NIHR）健康技术评估计划资助的独立研究，奖励号为NIHR128073。NIHR期刊图书馆网站https://doi.org/10.3310/HRCW7937上提供了这篇研究文章的简单语言摘要。
肺栓塞是一种潜在的严重疾病，血凝块导致肺部血液供应阻塞。肺栓塞的诊断是通过肺部扫描来进行的，通过显示血液由于血块而无法轻易通过血管的区域。肺栓塞的治疗包括抗凝药物（“血液稀释剂”），服用数月以上，包括华法林，肝素和直接作用的口服抗凝剂的可注射形式。这些药物的作用是防止新的凝块形成，同时身体自身的机制分解凝块。随着对肺栓塞的扫描技术越来越敏感,正在诊断更小的血凝块。然而,小的肺栓塞可能不会引起任何症状，并且可能由于其他原因在扫描中偶然发现。在这些情况下,目前尚不清楚肺栓塞是否需要治疗。这些远离肺中心的较小血管中的凝块（亚段肺栓塞）可以通过人体自身的机制来消除，而无需药物治疗。抗凝药物可引起一些患者的副作用，如出血。为了抗凝药物适合这些较小的肺栓塞，预防未来血栓(肺栓塞和深静脉血栓形成)的益处需要超过药物副作用带来的潜在风险.STOPAPE研究旨在通过测试我们是否可以安全地从诊断为亚段肺栓塞的患者中停止抗凝治疗来回答这个问题。尽管我们的目标是招募1466名患者参加试验，其中一半接受常规抗凝治疗，一半不接受抗凝治疗，我们无法足够快地招募患者参加试验，因此,我们无法继续STOPAPE研究。这项研究协议的发布是为了帮助希望回答这个研究问题的未来研究团队。
■自从出现计算机断层扫描肺动脉造影以调查疑似肺栓塞患者以来，亚段肺栓塞的诊断有所增加。对于通气/灌注不匹配，基于较旧的核医学诊断成像通常无法检测到亚段肺栓塞。随着计算机断层扫描肺血管造影对亚段肺栓塞的诊断增加，肺栓塞的病死率降低。亚段肺栓塞患者的最佳治疗方法越来越均衡，考虑到完全抗凝有显著的出血风险,并且以前通常不会通过通气/灌注扫描诊断出亚段肺栓塞,因此很可能在引入计算机断层扫描肺血管造影扫描之前主要不治疗.
■确定与在3个月、6个月和12个月完全抗凝治疗相比，对孤立性或偶发性亚段肺栓塞（即无并发深静脉血栓形成的亚段肺栓塞）停止抗凝治疗是否能减少复发性血栓栓塞和大出血的危害。确定孤立性亚段肺栓塞患者抗凝治疗（主要是出血）的并发症发生率。确定临床医生和患者是否可以接受不治疗孤立的亚段肺栓塞。确定一般报告放射科医师诊断的亚段肺栓塞的再分类率，由专业呼吸放射科医师进行审查，并制定一套规则来提高普通放射科医师对亚段肺栓塞的诊断。评估未使用抗凝治疗孤立性亚段肺栓塞患者的成本-效果，从卫生服务的角度来看。
■采用盲法终点委员会评估结果的前瞻性个体随机开放对照试验，用于复发性静脉血栓栓塞的非劣效性和出血事件的优越性。包括内部试验阶段，以确保不抗凝的可行性和可接受性。我们计划从至少50个急症医院招募1466名患者。允许15%的辍学率，这将使我们有90%的功效检测出主要和临床相关的非大出血,从抗凝组的7.3%减少到干预组的3%.我们有能力确定不抗凝的策略不劣于抗凝，在接受完全抗凝治疗的患者中，复发性静脉血栓栓塞的上限从预期的2％增加了2.3％。我们还计划进行一项研究，将所有计算机断层扫描肺血管造影照片中急性报告放射科医师对亚段肺栓塞的诊断与专业呼吸放射科医师进行比较。这将使我们能够在试点研究中确定安全性（即肺栓塞患者实际上比亚节段要大），并为普通放射科医生制定亚节段肺栓塞诊断指南。有血栓形成经验的患者对试验设计的所有方面都有贡献，并且是试验管理组的一部分。
STOPAPE试验因COVID大流行后的低招募率和国家卫生与护理研究所研究组合的优先恢复而过早停止。该试验没有结果数据。单独的NIHR图书馆出版物将详细介绍相关的定性研究，以检查患者和临床医生对孤立的亚段肺栓塞的抗凝治疗的看法，并介绍所有收集的招募患者的数据。
■本文介绍了由美国国立卫生与护理研究所（NIHR）健康技术评估计划资助的独立研究，奖励号为NIHR128073。NIHR期刊图书馆网站https://doi.org/10.3310/HRCW7937上提供了这篇研究文章的简单语言摘要。
肺栓塞是一种潜在的严重疾病，血凝块导致肺部血液供应阻塞。肺栓塞的诊断是通过肺部扫描来进行的，通过显示血液由于血块而无法轻易通过血管的区域。肺栓塞的治疗包括抗凝药物（“血液稀释剂”），服用数月以上，包括华法林，肝素和直接作用的口服抗凝剂的可注射形式。这些药物的作用是防止新的凝块形成，同时身体自身的机制分解凝块。随着对肺栓塞的扫描技术越来越敏感,正在诊断更小的血凝块。然而,小的肺栓塞可能不会引起任何症状，并且可能由于其他原因在扫描中偶然发现。在这些情况下,目前尚不清楚肺栓塞是否需要治疗。这些远离肺中心的较小血管中的凝块（亚段肺栓塞）可以通过人体自身的机制来消除，而无需药物治疗。抗凝药物可引起一些患者的副作用，如出血。为了抗凝药物适合这些较小的肺栓塞，预防未来血栓(肺栓塞和深静脉血栓形成)的益处需要超过药物副作用带来的潜在风险.STOPAPE研究旨在通过测试我们是否可以安全地从诊断为亚段肺栓塞的患者中停止抗凝治疗来回答这个问题。尽管我们的目标是招募1466名患者参加试验，其中一半接受常规抗凝治疗，一半不接受抗凝治疗，我们无法足够快地招募患者参加试验，因此,我们无法继续STOPAPE研究。这项研究协议的发布是为了帮助希望回答这个研究问题的未来研究团队。
