extended-duration versus short-duration pharmacological thromboprophylaxis in acutely ill hospitalized medical patients: a systematic review and meta-analysis of randomized controlled trials

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 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.