Comparative Effectiveness of Enoxaparin vs. Dalteparin for Thromboprophylaxis Aft

描述（由申请人提供）：创伤性损伤是美国发病率和死亡率的主要原因。1静脉血栓栓塞（VTE）是创伤患者的第4大常见并发症，2并且是该人群中可预防的发病率和死亡率的主要来源。在初次损伤后存活的患者中，肺栓塞（PE-VTE的一个子集）是第三大最常见的死亡原因。3低分子量肝素（LMWH）抗凝剂是该人群预防VTE的金标准。4然而，最有效的LMWH尚不清楚。尽管依诺肝素和达肝素是创伤患者中最常用的两种低分子肝素，但很少有研究评价其在该人群中的比较有效性。此外，可能减少的具体因素 对这两种药剂的有效性知之甚少。 该提案旨在通过以下广泛目标改善创伤患者的VTE预防：1）检查依诺肝素和达肝素的比较有效性~ 2）确定预测预防失败的患者和治疗因素~ 3）培训申请人药物流行病学方法，因为它们适用于危重创伤人群~和4）帮助申请人发展独立调查的职业生涯。申请人将利用宾夕法尼亚大学的资源来实现既定目标。 宾夕法尼亚大学是一个主要的创伤中心，并维护一个患者登记处，其中包含在宾夕法尼亚大学治疗的所有创伤患者的人口统计数据、损伤特征和结局。这些数据将与当地药房数据库和临床数据仓库的信息相关联，并将比较依诺肝素与达肝素患者的VTE发生率。此外，将开发风险预测模型，以识别尽管接受预防治疗仍发生VTE的患者。该预测工具将用于靶向患者，这些患者将在未来的研究中从额外的预防策略中获益。申请人将通过与高级研究员的直接一对一指导以及严格的研究方法教学培训计划来完成这些目标。作为NRSA提供的培训的结果，申请人将发展技能，以进行进一步的研究，重点是预防VTE作为K23职业发展奖的一部分。此外，由F32基金支持的项目成果将对创伤人群的静脉血栓栓塞预防产生直接影响。它将为正在寻找最有效药物的医院提供数据，并将确定预防失败的风险因素。这项研究的见解可能最终导致个性化给药方案的研究。

DESCRIPTION (provided by applicant): Traumatic injury is a leading cause of morbidity and mortality in the United States.1 Venous thromboembolism (VTE) is the 4th most common complication in trauma patients, 2 and represents a major source of preventable morbidity and mortality in this population. In patients who survive the initial injury, pulmonary embolism (PE- a subset of VTE) represents the 3rd most common cause of death.3 Low molecular weight heparin (LMWH) anticoagulants are the gold standard for prevention of VTE in this population.4 However, the most effective LMWH is unknown. Although enoxaparin and dalteparin are the two most commonly used LMWHs in trauma patients, there are few studies that have evaluated their comparative effectiveness in this population. In addition, specific factors that may decrease the effectiveness of both agents are poorly understood. The proposal aims to improve VTE prophylaxis in trauma patients through the following broad objectives: 1) Examine the comparative effectiveness of enoxaparin and dalteparin~ 2) Identify patient and treatment factors that predict failure of prophylaxis 3) train the applicant in methods of pharmacoepidemiology as they apply to the critically ill trauma population~ and 4) aid the applicant's evolution to a career in independent investigation. The applicant will leverage the resources of the University of Pennsylvania to achieve the stated objectives. Penn is a major trauma center and maintains a patient registry that contains demographics, injury characteristics, and outcomes for all trauma patients treated at Penn. These data will be linked to information from a local pharmacy database and clinical data warehouse, and the incidence of VTE will be compared in patients given enoxaparin versus dalteparin. In addition, a risk prediction model will be developed to identify patients that develop VTE despite receiving prophylaxis. This prediction tool will be used to target patients that would benefit from additiona prophylaxis strategies in future studies. The applicant will complete these objectives through direct one-on-one mentoring with a senior investigator and through a rigorous didactic training program in research methods. As a result of training provided by the NRSA, the applicant will develop the skills to conduct further research focusing on VTE prevention as part of a K23 career development award. Moreover, the results of the project supported by this F32 award will have an immediate impact on VTE prophylaxis in the trauma population. It will provide data to hospitals that are searching for the most effective agent, and it will identify risk factors for prophylaxis failure. Insights from this research may eventually lead to studies of personalized dosing regimens.