title: Extended-duration versus short-duration pharmacological thromboprophylaxis in acutely Ill hospitalized medical patients: a systematic review and meta-analysis of randomized controlled trials.
abstract: Extended-duration pharmacological thromboprophylaxis, for at least 28 days, is effective for the prevention of symptomatic venous thromboembolism (VTE) in high-risk surgical patients but is of uncertain benefit in hospitalized medical patients. We aimed to evaluate the efficacy and safety of extended-duration thromboprophylaxis in hospitalized medical patients. We conducted a systematic PubMed, Medline and EMBASE literature search until June 2016 and a meta-analysis of randomized controlled trials which compared extended-duration with short-duration thromboprophylaxis in hospitalized medical patients. Four randomized controlled trials comparing extended-duration prophylaxis (24-47 days) with short-duration prophylaxis (6-14 days) in a total of 34,068 acutely ill hospitalized medical patients were included. When compared with short-duration prophylaxis, extended-duration prophylaxis was associated with a decrease in symptomatic proximal or distal deep vein thrombosis (DVT) [relative risk (RR) = 0.52; 95% confidence interval (Cl): 0.35-0.77: p = 0.001; absolute risk reduction (ARR) = 0.32%, number needed to treat (NNT) = 313], and symptomatic non-fatal pulmonary embolism (RR = 0.61; 95% Cl 0.38-0.99: p = 0.04; ARR = 0.16%; NNT = 625), an increase in major bleeding (RR = 2.08; 95% Cl 1.50-2.90: p < 0.0001, absolute risk increase = 0.41%, number needed to harm = 244), and no significant reduction in VTE-related mortality (RR = 0.69; 95% Cl 0.45-1.06: p = 0.09) or all-cause mortality (RR = 1.00; 95% CI 0.89-1.12; p = 0.95). There was heterogeneity for major bleeding due to results from the APEX trial (no difference between betrixaban and enoxaparin). Compared with short-duration thromboprophylaxis, extended-duration treatment reduces the risk for symptomatic DVT and non-fatal pulmonary embolism. Extended treatment with apixaban, enoxaparin and rivaroxaban but not betrixaban increases the risk for major bleeding.
authors.affiliation: Portiuncula University Hospital and Galway University Hospital, Saolta University Health Care Group, Galway, Ireland. liew.aaron@gmail.com.|Clinical Science Institute, National University of Ireland Galway (NUIG), Galway, Ireland. liew.aaron@gmail.com.|Institute of Cellular Medicine, Newcastle University, Newcastle Upon Tyne, UK. liew.aaron@gmail.com.
authors.forename: Aaron Y L
authors.initials: AY
authors.lastname: Liew
authors.affiliation: Department of Medicine, Division of Hematology, McMaster University, Hamilton, ON, Canada.
authors.forename: Siavash
authors.initials: S
authors.lastname: Piran
authors.affiliation: Department of Medicine, Division of Hematology, McMaster University, Hamilton, ON, Canada.
authors.forename: John W
authors.initials: JW
authors.lastname: Eikelboom
authors.affiliation: Department of Medicine, Division of Hematology, McMaster University, Hamilton, ON, Canada.
authors.forename: James D
authors.initials: JD
authors.lastname: Douketis
mesh_terms: D000208:Acute Disease; D005343:Fibrinolytic Agents / Q000009:adverse effects / Q000627:therapeutic use; D006470:Hemorrhage / Q000139:chemically induced; D006760:Hospitalization; D006801:Humans; D011292:Premedication / Q000379:methods*; D016032:Randomized Controlled Trials as Topic; D013997:Time Factors; D016896:Treatment Outcome; D054556:Venous Thromboembolism / Q000150:complications / Q000517:prevention & control*
chemical_list: D005343:Fibrinolytic Agents
keywords: Acutely ill hospitalized medical patients; Extended pharmacological thromboprophylaxis; Meta-analysis