Downloaded from http://journals.lww.com/jtrauma by BhDMf5ePHKbH4TTImqenVHSKDBWmBJlGfyY0G05/GpI+6zTwcMtVXZjGaRi5koEC on 08/22/2020 Comparison of direct oral anticoagulant and vitamin K antagonists on outcomes among elderly and nonelderly trauma patients Takeshi Nishimura, MD, Francis X. Guyette, MD, Hiromichi Naito, MD, PhD, Atsunori Nakao, MD, PhD, Joshua B. Brown, MD, and Clifton W. Callaway, MD, PhD, Pittsburgh, Pennsylvania BACKGROUND: Direct oral anticoagulants (DOACs) are widely used among patients requiring anticoagulant therapy. These drugs are associated with a lower risk of bleeding than vitamin K antagonists (VKAs). However, the outcomes of elderly trauma patients receiving DOACs are not well known. METHODS: We reviewed data from trauma patients at our level I trauma center (University of Pittsburgh Medical Center, Presbyterian Hospital) seen from January 2011 to July 2018. We identified trauma patients taking DOACs or VKAs and compared these cohorts using 1:1 propensity score–matching based on patient characteristics, antiplatelet use, comorbidities, and laboratory values. The primary out- come was in-hospital mortality. Secondary outcomes included the proportion of patients discharged to skilled nursing facility/ rehabilitation facility discharge or to home, and transfusion volume. RESULTS: Of 32,272 trauma patients screened, 530 were taking DOACs and 1,702 were taking VKAs. We matched 668 patients in a 1:1 ratio (DOACs group, 334 vs. VKAs group, 334). The DOACs group had similar mortality (4.8% vs. 1.6%; odds ratio (OR), 3.0; 95% confidence interval (CI), 0.31–28.8; p = 0.31) among patients younger than 65 years, but mortality differed (3.0% vs. 6.6%; OR, 0.41; 95% CI, 0.17–0.99; p = 0.048) among patients older than 65 years. The proportion of patients discharged to skilled nursing facility/rehabilitation facility (50.0% vs. 50.6%; OR, 0.98; 95% CI, 0.72–1.32; p = 0.88) and to home (40.4% vs. 38.6%; OR, 1.08; 95% CI, 0.79–1.47; p = 0.64) were similar. Patients in the DOACs group received fewer fresh frozen plasma (p = 0.032), but packed red blood cells (p = 0.86) and prothrombin complex concentrate (p = 0.48) were similar. CONCLUSION: In this matched cohort of anticoagulated trauma patients, DOACs were associated with the decreased in-hospital mortality and de- creased administration of fresh frozen plasma compared with VKAs among trauma patients 65 years or older taking anticoagulant therapy. (J Trauma Acute Care Surg. 2020;89: 514–522. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.) LEVEL OF EVIDENCE: Prognostic/Epidemiological, level III. KEY WORDS: DOACs; VKA; trauma; propensity score matching; elderly. T rauma is the most common cause of death worldwide. Uncon- trolled hemorrhage remains the leading cause of preventable death in trauma. Anticoagulant drugs are necessary for disease management particularly among geriatric patients. Unfortunately, anticoagulant drugs also greatly increase the risk of hemorrhage in trauma. Since 1954, vitamin K antagonists (VKAs) such as Coumadin (warfarin) have been the core of outpatient anticoagula- tion therapy for atrial fibrillation (AF) and venous thromboembo- lism (VTE). These agents prevent blood clotting but increase the risk for adverse outcomes after traumatic injury. Preinjury VKAs use is associated with an increased risk of mortality among trauma patients, 1 including a 40% increased odds of intracranial hemor- rhage (ICH) and doubled 30-day mortality in head trauma patients. 2 Direct oral anticoagulants (DOACs), sometimes called novel oral anticoagulants, entered use in 2011. Consistent with the International Society on Thrombosis and Haemostasis recom- mendation, we will refer to the drug class as DOACs. Dabigatran (Pradaxa), rivaroxaban (Xarelto), apixaban (Eliquis), and edoxaban (Savaysa) are approved for the prevention of stroke in patients with AF and are thought to have a lower risk of bleeding compared with VKAs. Direct oral anticoagulants are also effec- tive and safe for the prevention and treatment of VTE and pulmo- nary embolism. 3 A meta-analysis performed compared VKAs and DOACs and concluded that there was no difference in fatal outcomes from bleeding between VKAs and DOACs use. 4 However, few studies address the safety of DOACs in the context of trauma especially among elderly patients. Studies com- paring the effect of DOACs and VKAs on outcomes following traumatic ICH are inconclusive. 5,6 We hypothesize that compared with VKAs, DOACs are associated with decreased mortality among trauma patients requiring anticoagulant therapy. We per- formed a secondary analysis to determine if age modified the ef- fect of anticoagulants (DOACs or VKAs) on mortality. PATIENTS AND METHODS Study Designs and Data Collection We performed a retrospective, single-center, cohort study of patients treated with either VKAs or DOACs who presented as a trauma team activation. The Human Research Protection Submitted: August 26, 2019, Revised: May 5, 2020, Accepted: May 28, 2020, Pub- lished online: June 10, 2020. From the Department of Emergency Medicine (T.N., F.X.G., C.W.C.), University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Emergency and Critical Care Medicine (T.N.), Hyogo Emergency Medical Center, Hyogo; Department of Emergency and Critical Care Medicine (T.N., H.N., A.N.), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan; and Department of Surgery (J.B.B.), Division of Trauma and General Sur- gery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal’s Web site (www.jtrauma.com). Address for reprints: Takeshi Nishimura, MD, Department of Emergency Medicine, University of Pittsburgh, 3600 Forbes Ave., Iroquois Building, Pittsburgh, PA 15261; email: kogushi1@msn.com. DOI: 10.1097/TA.0000000000002823 ORIGINAL ARTICLE 514 J Trauma Acute Care Surg Volume 89, Number 3 Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.