Prediction of Anticoagulant-Related Bleeding Risk in Patients with Cancer

癌症患者抗凝相关出血风险的预测

• 批准号: 10566861
• 负责人: Kristen Marie Sanfilippo
• 金额: $ 40.24万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-01-05 至 2026-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10566861
• 关键词: Address; Anticoagulant therapy; Anticoagulants; Area; Atrial Fibrillation; Calibration; Cancer Burden; Cancer Patient; Cessation of life; Clinical Trials; Data; Development; Diagnosis; Discrimination; Effectiveness; Enrollment; Equilibrium; Fatality rate; Goals; Guidelines; Health Personnel; Hemorrhage; High-Risk Cancer; Histology; Individual; Intervention; Knowledge; Length; Location; Malignant Neoplasms; Methods; Modeling; Morbidity - disease rate; National Comprehensive Cancer Network; Oral; Patient Care; Patients; Performance; Periodicals; Population; Positioning Attribute; Prevention; Prevention approach; Prophylactic treatment; Provider; Recommendation; Recurrence; Research; Risk; Risk Factors; Risk-Benefit Assessment; Thrombosis; Time; Treatment-Related Cancer; United States; Venous; burden of illness; cancer risk; clinical predictive model; cohort; evidence base; high risk; high risk population; improved; innovation; mortality; novel; patient oriented; personalized approach; predictive modeling; prevent; randomized trial; risk prediction model; success; time use; treatment center; tumor; venous thromboembolism

Project Summary Among patients with cancer, the risk of anticoagulant-related major bleeding is more than double that of patients without cancer. These bleeds have a fatality rate of 7%. Current guidelines recommend indefinite anticoagulant therapy in many patients with cancer and venous thromboembolism (VTE) with periodic assessments of bleeding risk. However, no evidence-based models exist to quantify bleeding risk in patients with cancer taking anticoagulants. In addition, recent trials have demonstrated effectiveness of direct oral anticoagulants as primary prophylaxis for prevention of initial VTE in patients with cancer. Thus, there is a strong need to balance the competing risks of VTE and anticoagulant-related bleeding in patients with cancer. While there are models that quantify bleeding risk in non-cancer populations (i.e. atrial fibrillation, non- cancer associated VTE) taking anticoagulants, they have not been validated in patients with cancer. Quantification of bleeding risk in patients with cancer and VTE would allow for an evidence-based approach to preventing and treating VTE by minimizing anticoagulant therapy in patients at high-risk of bleeding and allowing for judicial use in patients at low-risk of bleeding. The overall objective of this study is to develop a prediction model for anticoagulant-related bleeding in patients with cancer and VTE on anticoagulant therapy and to calibrate that model in cancer patients at high-risk of VTE being considered for primary thromboprophylaxis with anticoagulant therapy. We will accomplish our overall objective through the following specific aims: (1) validate eight existing bleeding prediction models in a cohort of 7489 patients with cancer and VTE receiving anticoagulant therapy, (2) refine and validate a cancer-specific prediction model to quantify risk of anticoagulant-associated bleeding in patients with cancer on anticoagulant therapy for VTE, and (3) calibrate the refined bleeding prediction model in a cohort of patients with cancer receiving primary anticoagulant thromboprophylaxis enrolled in two randomized trials (AVERT and CASSINI). These aims will be addressed with an expert research team in the areas of bleeding, VTE (especially in patients with cancer) and development and implementation of risk prediction models. This proposal is innovative as it addresses a current gap in the management of patients with cancer with or at high-risk of VTE by developing a prediction model to quantify the risk of the intervention (anticoagulant therapy) to inform and guide patient care. This research will be significant because it has the potential to decrease anticoagulant-related bleeding and thus bleeding related morbidity and mortality in patients with cancer.

项目摘要 在癌症患者中，与抗凝剂相关的主要出血的风险是 没有癌症的患者。这些出血的死亡率为7％。当前指南建议不确定 许多癌症患者和静脉血栓栓塞（VTE）的抗凝治疗 评估出血风险。但是，尚无基于证据的模型来量化患者的出血风险 服用抗凝剂。此外，最近的试验证明了直接口头的有效性 抗凝剂作为预防癌症患者初始VTE的主要预防。因此，有一个 强烈需要平衡VTE的竞争风险和与患者的抗凝剂相关出血 癌症。虽然有一些模型可以量化非癌症人群中出血风险（即心房颤动，非 - 非癌症 与癌症相关的VTE）服用抗凝剂，尚未在癌症患者中得到验证。 量化癌症和VTE患者出血风险的量化将允许一种基于证据的方法 通过最大程度地减少出血高风险和 允许在低风险出血的患者中司法使用。这项研究的总体目的是开发 抗凝抗凝治疗患者和VTE患者的抗凝剂相关出血的预测模型 并校准该模型在高风险的癌症患者中被考虑用于主要的VTE 通过抗凝治疗的血栓预防。我们将通过以下来实现我们的整体目标 具体目的：（1）验证7489例癌症患者队列中现有的八个现有出血预测模型 和接受抗凝治疗的VTE，（2）完善并验证癌症特异性预测模型以量化 VTE抗凝治疗癌症患者患抗凝剂相关的出血风险，（3） 在接受初次的癌症患者队列中校准精致的出血预测模型 在两项随机试验（AWTH和CASSINI）中招募的抗凝药物预防症。这些目标将是 与出血领域的专家研究团队（尤其是在癌症患者中）和 风险预测模型的开发和实施。该建议是创新的，因为它解决了 通过建立预测，当前患有癌症患者患者或高危VTE患者的差距 量化干预风险（抗凝治疗）以告知和指导患者护理的模型。这 研究将是重要的，因为它有可能减少抗凝剂相关的出血，因此有可能 癌症患者的出血相关发病率和死亡率。