{"abstracts":[{"sha1":"7723274ba950655a621654e1c038df7a16f4f004","content":"\nBackground\nLower limb trauma requiring immobilization is a significant contributor to overall venous thromboembolism (VTE) burden. The clinical effectiveness of thromboprophylaxis for this indication and the optimal agent strategy are still a matter of debate. Our main objective was to assess the efficacy of pharmacological thromboprophylaxis to prevent VTE in patients with isolated temporary lower limb immobilization after trauma. We aimed to estimate and compare the clinical efficacy and the safety of the different thromboprophylactic treatments to determine the best strategy.\n\n\nMethods and findings\nWe conducted a systematic review and a Bayesian network meta-analysis (NMA) including all available randomized trials comparing a pharmacological thromboprophylactic treatment to placebo or to no treatment in patients with leg immobilization after trauma. We searched Medline, Embase, and Web of Science until July 2021. Only RCT or observational studies with analysis of confounding factors including adult patients requiring temporary immobilization for an isolated lower limb injury treated conservatively or surgically and assessing pharmacological thromboprophylactic agents or placebo or no treatment were eligible for inclusion. The primary endpoint was the incidence of major VTE (proximal deep vein thrombosis, symptomatic VTE, and pulmonary embolism-related death). We extracted data according to Preferred Reporting Items for Systematic Reviews and Meta-analyses for NMA and appraised selected trials with the Cochrane review handbook. Fourteen studies were included (8,198 patients). Compared to the control group, rivaroxaban, fondaparinux, and low molecular weight heparins were associated with a significant risk reduction of major VTE with an odds ratio of 0.02 (95% credible interval (CrI) 0.00 to 0.19), 0.22 (95% CrI 0.06 to 0.65), and 0.32 (95% CrI 0.15 to 0.56), respectively. No increase of the major bleeding risk was observed with either treatment. Rivaroxaban has the highest likelihood of being ranked top in terms of efficacy and net clinical benefit. The main limitation is that the network had as many indirect comparisons as direct comparisons.\n\n\nConclusions\nThis NMA confirms the favorable benefit/risk ratio of thromboprophylaxis for patients with leg immobilization after trauma with the highest level of evidence for rivaroxaban.\n\n\nTrial registration\nPROSPERO CRD42021257669.\n","mimetype":"application/xml+jats"}],"refs":[{"index":0,"extra":{"authors":["B Nemeth"],"doi":"10.1016/j.thromres.2018.11.030","volume":"174"},"key":"pmed.1004059.ref001","year":2019,"container_name":"Thromb Res","title":"Venous thrombosis following lower-leg cast immobilization and knee arthroscopy: From a population-based approach to individualized therapy","locator":"62"},{"index":1,"extra":{"authors":["K Grewal"]},"key":"pmed.1004059.ref002","year":2021,"container_name":"Ann Emerg Med","title":"Venous Thromboembolism in Patients Discharged From the Emergency Department With Ankle Fractures: A Population-Based Cohort Study"},{"index":2,"extra":{"authors":["RA van Adrichem"],"doi":"10.1056/nejmoa1613303","volume":"376"},"key":"pmed.1004059.ref003","year":2017,"container_name":"N Engl J Med","title":"Thromboprophylaxis after Knee Arthroscopy and Lower-Leg Casting","locator":"515"},{"index":3,"extra":{"authors":["MM Bruntink"],"doi":"10.1016/j.injury.2017.02.018","volume":"48"},"key":"pmed.1004059.ref004","year":2017,"container_name":"Injury","title":"Nadroparin or fondaparinux versus no thromboprophylaxis in patients immobilised in a below-knee plaster cast (PROTECT): A randomised controlled trial","locator":"936"},{"index":4,"extra":{"authors":["X Zheng"],"doi":"10.1177/1071100716658953","volume":"37"},"key":"pmed.1004059.ref005","year":2016,"container_name":"Foot Ankle Int","title":"Effect of Chemical Thromboprophylaxis on the Rate of Venous Thromboembolism After Treatment of Foot and Ankle Fractures","locator":"1218"},{"index":5,"extra":{"authors":["CM Samama"],"doi":"10.1056/nejmoa1913808","volume":"382"},"key":"pmed.1004059.ref006","year":2020,"container_name":"N Engl J Med","title":"Rivaroxaban or Enoxaparin in Nonmajor Orthopedic Surgery","locator":"1916"},{"index":6,"extra":{"authors":["S Haque"],"doi":"10.1016/j.fas.2015.02.002","volume":"21"},"key":"pmed.1004059.ref007","year":2015,"container_name":"Foot Ankle Surg","title":"Oral thromboprophylaxis in patients with ankle fractures immobilized in a below the knee cast.","locator":"266"},{"index":7,"extra":{"authors":["Y Falck-Ytter"],"doi":"10.1378/chest.11-2404","volume":"141"},"key":"pmed.1004059.ref008","year":2012,"container_name":"Chest","title":"Prevention of VTE in Orthopedic Surgery Patients.","locator":"e278S"},{"index":8,"extra":{"authors":["C-M Samama"],"volume":"30"},"key":"pmed.1004059.ref009","year":2011,"container_name":"Update 2011. 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A systematic review and meta-analysis","locator":"19"},{"index":38,"extra":{"authors":["AA Zee"]},"key":"pmed.1004059.ref039","year":2017},{"index":39,"extra":{"authors":["S Lewis"],"doi":"10.1016/s2352-3026(19)30155-3"},"key":"pmed.1004059.ref040","year":2019,"container_name":"Lancet Haematol","title":"Venous thromboembolism prophylaxis strategies for people undergoing elective total knee replacement: a systematic review and network meta-analysis","locator":"e530"},{"index":40,"extra":{"authors":["A Afshari"],"doi":"10.1097/eja.0000000000000729","volume":"35"},"key":"pmed.1004059.ref041","year":2018,"container_name":"Eur J Anaesthesiol","title":"European Guidelines on perioperative venous thromboembolism prophylaxis: Executive summary.","locator":"77"},{"index":41,"extra":{"authors":["IA Ali"],"doi":"10.1007/s11845-020-02306-3","volume":"190"},"key":"pmed.1004059.ref042","year":2021,"container_name":"Ir J Med Sci","title":"Venous thromboembolism in trauma patients with lower limb cast immobilization, associated risk reduction and complication using rivaroxaban","locator":"169"},{"index":42,"extra":{"authors":["D Douillet"],"doi":"10.1097/mej.0000000000000677","volume":"27"},"key":"pmed.1004059.ref043","year":2020,"container_name":"Eur J Emerg Med","title":"Evidence-based guidelines for thromboprophylaxis in patients with lower limb trauma requiring immobilization: an urgent, unmet need.","locator":"245"},{"index":43,"extra":{"authors":["B Nemeth"],"doi":"10.1016/j.eclinm.2020.100270","volume":"20"},"key":"pmed.1004059.ref044","year":2020,"container_name":"EClinicalMedicine","title":"Clinical risk assessment model to predict venous thromboembolism risk after immobilization for lower-limb trauma","locator":"100270"},{"index":44,"extra":{"authors":["JH Elliott"],"doi":"10.1016/j.jclinepi.2017.08.010","volume":"91"},"key":"pmed.1004059.ref045","year":2017,"container_name":"J Clin Epidemiol","title":"Living systematic review: 1. Introduction-the why, what, when, and how.","locator":"23"},{"index":45,"extra":{"authors":["JJ Bartoszko"],"doi":"10.1136/bmj.n949","volume":"373"},"key":"pmed.1004059.ref046","year":2021,"container_name":"BMJ","title":"Prophylaxis against covid-19: living systematic review and network meta-analysis","locator":"n949"},{"index":46,"extra":{"authors":["D Douillet"],"doi":"10.1371/journal.pone.0217748","volume":"14"},"key":"pmed.1004059.ref047","year":2019,"container_name":"PLoS ONE","title":"Venous thromboembolism risk stratification for patients with lower limb trauma and cast or brace immobilization","locator":"e0217748"}],"contribs":[{"index":0,"creator_id":"dusgojfjtzhpdk7b6mw4cy5m5e","creator":{"orcid":"0000-0001-7986-7552","surname":"douillet","given_name":"delphine","display_name":"delphine douillet","state":"active","ident":"dusgojfjtzhpdk7b6mw4cy5m5e","revision":"f970fbdb-3823-40d1-b0eb-5d20c74fea5a"},"raw_name":"D. 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