Efficacy and Safety of Therapeutic-Dose Heparin vs Standard Prophylactic or Intermediate-Dose Heparins for Thromboprophylaxis in High-risk Hospitalized Patients With COVID-19

作者：Alex C. Spyropoulos, Mark Goldin, Dimitrios Giannis, Wassim Diab, Janice Wang, Sameer Khanijo, Andrea Mignatti, Eugenia Gianos, Marc Cohen, Gulru Sharifova, J Lund, Alfonso Tafur, Paul A. Lewis, Kevin P. Cohoon, Husneara Rahman, Cristina Sison, Martin Lesser, Kanta Ochani, Nirav Agrawal, Judith Hsia, Victoria E. Anderson, Marc P. Bonaca, Jonathan L. Halperin, Jeffrey I. Weitz, HEP-COVID Investigators, Lori Ohanesian, Michelle Glater, Christopher C.K. Ho, Annamaria Iakovou, Daniel Ying, Manile Dastagir, Alex Convissar, Seerat Aujla, Elizabeth Mathew, Vani Thiyagarajan, Tricia Lewis, Luis Gruberg, Paul Maccaro, Dana Kuziw, Bhumi Pandhi, George Surguladze, Ashley M. Eapen, A. Pantea, PHYLLIS SUEN, John P. Flynt, Michael Krzyzak, Kamal Sharma, Amanda Steadham, Sherry McLean, Karen Herring, Karen Maroney, Kambiz Zorriasateyn, Bernardo Vargas‐Leitón, Marisa Durante, Ujala Bhokary, Linda Pierchala, Elizabeth A. Fisher, Debi L. Oxenberg, Alison Sabados, Omair A. Chaudhary, Shelley Schultz, S. Cotey, Connie N. Hess, Hope Cruse, Daniel Uy, Sunita Sharma, Kevin Molina, Daliya Jagat, Bandyopadhyay Dehali · 发表于：JAMA Internal Medicine · 年份：2021 · DOI：10.1001/jamainternmed.2021.6203 · 被引用次数：488 · 研究领域：COVID-19 Clinical Research Studies、Heparin-Induced Thrombocytopenia and Thrombosis、Venous Thromboembolism Diagnosis and Management

Importance: Hospitalized patients with COVID-19 are at risk for venous and arterial thromboembolism and death. Optimal thromboprophylaxis dosing in high-risk patients is unknown. Objective: To evaluate the effects of therapeutic-dose low-molecular-weight heparin (LMWH) vs institutional standard prophylactic or intermediate-dose heparins for thromboprophylaxis in high-risk hospitalized patients with COVID-19. Design, Setting, and Participants: The HEP-COVID multicenter randomized clinical trial recruited hospitalized adult patients with COVID-19 with D-dimer levels more than 4 times the upper limit of normal or sepsis-induced coagulopathy score of 4 or greater from May 8, 2020, through May 14, 2021, at 12 academic centers in the US. Interventions: Patients were randomized to institutional standard prophylactic or intermediate-dose LMWH or unfractionated heparin vs therapeutic-dose enoxaparin, 1 mg/kg subcutaneous, twice daily if creatinine clearance was 30 mL/min/1.73 m2 or greater (0.5 mg/kg twice daily if creatinine clearance was 15-29 mL/min/1.73 m2) throughout hospitalization. Patients were stratified at the time of randomization based on intensive care unit (ICU) or non-ICU status. Main Outcomes and Measures: The primary efficacy outcome was venous thromboembolism (VTE), arterial thromboembolism (ATE), or death from any cause, and the principal safety outcome was major bleeding at 30 ± 2 days. Data were collected and adjudicated locally by blinded investigators via imagin...