Extended thromboprophylaxis with low-molecular-weight heparins after hospital discharge in high-risk surgical and medical patients: A review

Background: Prophylaxis against venous thromboembolism (VTE) is routinely administered during the hospital stay in at-risk surgical and medical patients. However, in high-risk groups, the risk of deep-vein thrombosis or pulmonary embolism may persist for several weeks after discharge. The standard duration of thromboprophylaxis (6-14 days) may not provide adequate protection against such events. Objective: This article reviews published data on the efficacy and safety profile of extended-duration thromboprophylaxis in patients at high risk for VTE, the potential cost-effectiveness of such treatment, and practical aspects of ensuring an effective transition from the inpatient to the outpatient setting. Methods: MEDLINE and the Cochrane Database of Systematic Reviews were searched through January 2009 for relevant English-language reports of clinical trials, abstracts, and case reports. The search terms included, but were not limited to, venous thromboembolism, pulmonary embolism, anticoagulation, thromboprophylaxis, prolonged duration, and extended duration. The reference lists of the identified articles were reviewed for additional relevant publications. Congress Web sites were also consulted. The principal criteria for inclusion of a study were that it have a prospective, randomized design and include a control group. Case series and retrospective analyses were excluded. Results: Studies have found that extended-duration thromboprophylaxis (28-45 days) with low-molecular-weight heparins (LMWHs) can reduce the risk of VTE in high-risk patients. In separate meta-analyses, extended-duration thromboprophylaxis with LMWH was associated with significant reductions in the likelihood of symptomatic VTE compared with standard-duration thromboprophylaxis in patients undergoing major orthopedic surgery (odds ratio [OR] = 0.38; 95% CI, 0.24-0.61) or major abdominal or pelvic surgery (Peto OR = 0.22; 95% CI, 0.06-0.80). There was large heterogeneity in the reported rates of major and minor bleeding. The occurrence of clinically relevant bleeding events was generally low (<1%), particularly during extended prophylaxis. Extended-duration thromboprophylaxis was cost-effective compared with standard-duration thromboprophylaxis, with increased pharmacy costs offset by reductions in VTE and the associated costs of hospitalization. Conclusions: In high-risk surgical and medical patients, the risk of VTE may extend beyond the period of hospitalization. Such patients may benefit from extended-duration thromboprophylaxis to reduce the risk of late VTE events. LMWHs were efficacious, were associated with low rates of clinically relevant bleeding complications, and were cost-effective in patients at high risk for VTE.