Contemporary Venous Thromboembolism Treatment

项目总结/摘要 静脉血栓栓塞（VTE），包括深静脉血栓形成和肺栓塞， 每年影响350，000至600，000美国人，并导致超过100，000人死亡。这 使静脉血栓栓塞成为心血管死亡的第三大原因，仅次于心脏病发作和中风。治疗 VTE事件最好从3个阶段的角度进行评估：急性（前5-10天），主要治疗（第一次）， 事件后6个月）和二级预防（事件后≥6个月）。传统上静脉血栓栓塞是急性治疗 住院期间，华法林用于一级治疗和二级预防。最近有 VTE治疗的两个主要进展：1）急性期VTE的门诊治疗，2） 2012年批准直接口服抗凝剂（DOAC）用于VTE一级治疗和二级预防。 随机试验表明，门诊VTE管理和DOAC（即达比加群， 利伐沙班、阿哌沙班、依度沙班）至少与它们的传统替代物一样有效。然而，在这方面， 随机试验并不总是可推广到通常的临床环境，并且通常动力不足， 确定不良结局风险最高的亚组。此外，DOAC的安全性问题也已引起关注。 因此，需要进行更多的研究，以确定与传统替代品相比， 这些新的治疗策略，他们的风险，并确定患者亚组更有可能经历 利或弊。比较有效性研究可以在“现实世界”环境中解决这些问题。 使用来自美国两个大型商业索赔数据库Optum和MarketScan的数据，其中包括 超过500，000例静脉血栓栓塞患者，我们建议评估与住院与 急性期门诊管理，DOAC与华法林作为VTE的主要治疗，以及 DOAC与华法林与无抗凝治疗用于VTE二级预防。主要结局 包括复发性VTE、颅内出血和死亡率。我们还将确定患者亚组， 按年龄、性别、人种/种族、合并症、使用其他药物和索引VTE表现（无诱因， 诱发的非癌症，癌症相关），DOAC对其特别有益或有害。此外，本发明还 我们将开发首个VTE复发、颅内出血和死亡率的风险预测模型， 合并DOAC。这些预测模型将对临床实践产生直接和直接的影响， 帮助临床医生和患者决定最合适的抗凝治疗。NHLBI有 将抗凝治疗列为比较有效性研究的首要任务。 总之，这项研究的结果将立即影响临床实践，加强或导致 重新考虑现有的VTE管理临床指南。此外，与2015年 精准医学倡议，这项研究将直接告知量身定制的治疗策略， 优化患者治疗效果。

Project Summary/Abstract Venous thromboembolism (VTE), which includes both deep vein thrombosis and pulmonary embolism, annually affects between 350,000 and 600,000 Americans and results in more than 100,000 deaths. This makes VTE the third leading cause of cardiovascular mortality, behind heart attack and stroke. Treatment of VTE events is best evaluated from the perspective of 3 phases: acute (first 5-10 days), primary treatment (first 6 months post-event) and secondary prevention (≥6 months post-event). Traditionally VTE was treated acutely in-hospital, and warfarin was used for primary treatment and secondary prevention. Recently there have been two major advances in the treatment of VTE: 1) the outpatient treatment of VTE in the acute phase, and 2) the approval in 2012 of direct oral anticoagulants (DOACs) for VTE primary treatment and secondary prevention. Randomized trials have demonstrated that outpatient VTE management and DOACs (i.e. dabigatran, rivaroxaban, apixaban, edoxaban) are at least as effective as their traditional alternatives. However, randomized trials are not always generalizable to the usual clinical setting, and are typically underpowered to identify subgroups most at risk for adverse outcomes. Moreover, safety concerns have been raised for DOACs. As such, additional research is needed to determine, relative to their traditional alternatives, the effectiveness of these new treatment strategies, their risks, and to identify patient subgroups more likely to experience benefit or harm. Comparative effectiveness research can address these questions in “real-world” settings. Using data from two large U.S. commercial claims databases, Optum and MarketScan, which include more than 500,000 patients with VTE, we propose to evaluate risks and benefits associated with inpatient vs. outpatient management in the acute phase, DOACs versus warfarin for the primary treatment of VTE, and DOACs versus warfarin versus no anticoagulant therapy for VTE secondary prevention. Primary outcomes include recurrent VTE, intracranial hemorrhage, and mortality. We will also identify patient subgroups, defined by age, sex, race/ethnicity, comorbidities, use of other medications, and index VTE presentation (unprovoked, provoked non-cancer, cancer-related) for which DOACs are particularly beneficial or hazardous. Additionally, we will develop the first risk prediction models for VTE recurrence, intracranial hemorrhage and mortality which incorporate DOACs. These predictive models will have a direct and immediate impact on clinical practice, helping clinicians and patients make decisions about the most appropriate anticoagulant therapy. NHLBI has listed anticoagulant therapies as a top priority for comparative effectiveness research. In sum, findings from this research would immediately impact clinical practice, reinforcing or leading to reconsideration of the existing clinical guidelines for VTE management. Further, in harmony with the 2015 Precision Medicine Initiative, this research would directly inform tailored treatment strategies, thereby optimizing patient outcomes.