Background This an update of the review first published in 2009. Major abdominal and pelvic surgery carries a high risk of venous thromboembolism (VTE). The efficacy of thromboprophylaxis with low molecular weight heparin (LMWH) administered during the in-hospital period is well-documented, but the optimal duration of prophylaxis after surgery remains controversial. Some studies suggest that patients undergoing major abdominopelvic surgery benefit from prolongation of the prophylaxis up to 28 days after surgery. Objectives To evaluate the efficacy and safety of prolonged thromboprophylaxis with LMWHfor at least 14 days after abdominal or pelvic surgery compared with thromboprophylaxis administered during the in-hospital period only in preventing late onset VTE. Search methods We performed electronic searches on 28 October 2017 in the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, LILACS and registered trials (Clinicaltrials.gov October 28, 2017 andWorldHealthOrganization International Clinical Trials Registry Platform (ICTRP) 28 October 2017). Abstract books from major congresses addressing thromboembolism were handsearched from 1976 to 28 October 2017, as were reference lists from relevant studies. Selection criteria We assessed randomized controlled clinical trials (RCTs) comparing prolonged thromboprophylaxis (=fourteen days) with any LMWH agent with placebo, or other methods, or both to thromboprophylaxis during the admission period only. The population consisted of persons undergoing abdominal or pelvic surgery for both benign and malignant pathology. The outcome measures included VTE (deep venous thrombosis (DVT) or pulmonary embolism (PE)) as assessed by objective means (venography, ultrasonography, pulmonary ventilation/perfusion scintigraphy, spiral computed tomography (CT) scan or autopsy). We excluded studies exclusively reporting on clinical diagnosis of VTE without objective confirmation. Data collection and analysis Review authors identified studies and extracted data. Outcomes were VTE (DVT or PE) assessed by objective means. Safety outcomes were defined as bleeding complications and mortality within three months after surgery. Sensitivity analyses were also performed with unpublished studies excluded, and with study participants limited to those undergoing solely open and not laparoscopic surgery. We used a fixed-effect model for analysis. Main results We identified seven RCTs (1728 participants) evaluating prolonged thromboprophylaxis with LMWH compared with control or placebo. The searches resulted in 1632 studies, of which we excluded 1528. One hundred and four abstracts, eligible for inclusion, were assessed of which seven studies met the inclusion criteria. For the primary outcome, the incidence of overall VTE after major abdominal or pelvic surgery was 13.2% in the control group compared to 5.3% in the patients receiving out-of-hospital LMWH (Mantel Haentzel (M-H) odds ratio (OR) 0.38, 95% confidence interval (CI) 0.26 to 0.54; I2 = 28%; moderate-quality evidence). For the secondary outcome of all DVT, seven studies, n = 1728, showed prolonged thromboprophylaxis with LMWH to be associated with a statistically significant reduction in the incidence of all DVT (M-H OR 0.39, 95% CI 0.27 to 0.55; I2 = 28%; moderate-quality evidence). We found a similar reduction when analysis was limited to incidence in proximal DVT (M-H OR 0.22, 95% CI 0.10 to 0.47; I2 = 0%; moderate-quality evidence). The incidence of symptomatic VTE was also reduced from 1.0% in the control group to 0.1% in patients receiving prolonged thromboprophylaxis (M-H OR 0.30, 95% CI 0.08 to 1.11; I2 = 0%; moderate-quality evidence). No difference in the incidence of bleeding between the control and LMWH group was found, 2.8% and 3.4%, respectively (M-H OR 1.10, 95% CI 0.67 to 1.81; I2 = 0%; moderate-quality evidence). No difference in mortality between the control and LMWH group was found, 3.8% and 3.9%, respectively (M-H OR 1.15, 95% CI 0.72 to 1.84; moderate-quality evidence). Estimates of heterogeneity ranged between 0% and 28% depending on the analysis, suggesting low or unimportant heterogeneity. Authors' conclusions Prolonged thromboprophylaxis with LMWH significantly reduces the risk of VTE compared to thromboprophylaxis during hospital admittance only, without increasing bleeding complications ormortality aftermajor abdominal or pelvic surgery. This finding also holds true for DVT alone, and for both proximal and symptomatic DVT. The quality of the evidence is moderate and provides moderate support for routine use of prolonged thromboprophylaxis.Given the low heterogeneity between studies and the consistent andmoderate evidence of a decrease in risk for VTE, our findings suggest that additional studies may help refine the degree of risk reduction but would be unlikely to significantly influence these findings. This updated review provides additional evidence and supports the previous results reported in the 2009 review.
Bibliographical noteFunding Information:
In the Jørgensen 2002 study, the venograms were re-evaluated by the same radiologists who assessed the venograms in the study by Lausen and colleagues (Lausen 1998), in order to perform a meta-analysis with the results of the study of Lausen and colleagues, introducing the possibility of bias (Jørgensen 2002). In Lausen 1998, a prespecified definition of bleeding complication was not used, and rather specific bleeding complications were listed, leaving which complications were considered bleeding complications open to interpretation. Sakon 2010 was supported by a pharmaceutical manufacturer, which also provided editorial support. The principal investigator reported several relevant conflicts of interest.
Modified intention-to-treat analysis of patients reaching an evaluable VTE end point (venogram or objection verification of symptomatic VTE) Study and editorial support financially supported by Sanofi-Aventis K.K., Japan. The principle investigator (MS) reported con-
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