Comparative Effectiveness of Enoxaparin vs. Dalteparin for Thromboprophylaxis Aft

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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.