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Meta-Analysis
. 2018 Nov 27;11(11):CD004318.
doi: 10.1002/14651858.CD004318.pub3.

Prolonged thromboprophylaxis with low molecular weight heparin for abdominal or pelvic surgery

Seth Felder  1 , Morten Schnack Rasmussen, Ray King, Bradford Sklow, Mary Kwaan, Robert Madoff, Christine Jensen
Affiliations
Meta-Analysis

Prolonged thromboprophylaxis with low molecular weight heparin for abdominal or pelvic surgery

Seth Felder et al. Cochrane Database Syst Rev. .

Update in

Abstract

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 LMWH for 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 and World Health Organization 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 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%; seven studies, n = 1728; 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 (HM-H OR 1.10, 95% CI 0.67 to 1.81; I2 = 0%; seven studies, n = 2239; 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 after major 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 and moderate 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.

PubMed Disclaimer

Conflict of interest statement

MSR is a member the advisory board of Pfizer, Denmark.

One author has been investigators on three of the randomized trials included in this review update (Rasmussen 2006).

Figures

Figure 1
Figure 1
Study flow diagram The primary search performed resulted 1698 studies, of which 1528 were excluded by reviewing the title and or removing duplicates, 104 were selected to be evaluated by the abstract, of these seven met the inclusion criteria. We excluded 97 studies by the primary selection because they lacked inclusion of patients undergoing abdominal or pelvic surgery, did not address thromboprophylaxis beyond day 14 after surgery, or were not clinical controlled trials. One trial were excluded as it was a double publication (Rasmussen 2003), and one because it was a review (Rasmussen 2003a). In addition, we found one trial by handsearching and only as an abstract presentation, and was reported as unpublished data (Jørgensen 2002). One study is actively recruiting patients (Zheng 2017), however, study methodology was not explicity outlined in the trial protocol.
Figure 2
Figure 2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Figure 3
Figure 3
Forest plot of comparison: 1 LMWH versus placebo, outcome: 1.1 All VTE.
Figure 4
Figure 4
Forest plot of comparison: 1 LMWH versus placebo, outcome: 1.6 All VTE (Subgroup analysis: Open resections only, laparoscopic excluded (Vedovati 2014)).
Figure 5
Figure 5
Forest plot of comparison: 1 LMWH versus placebo, outcome: 1.8 All VTE (Sensitivity analysis: Unpublished study excluded (Jørgensen 2002)).
Figure 6
Figure 6
Forest plot of comparison: 1 LMWH versus placebo, outcome: 1.2 All DVT.
Figure 7
Figure 7
Forest plot of comparison: 1 LMWH versus placebo, outcome: 1.7 All DVT (Subgroup analysis: Open resections only, laparoscopic excluded (Vedovati 2014)).
Figure 8
Figure 8
Forest plot of comparison: 1 LMWH versus placebo, outcome: 1.9 All DVT (Sensitivity analysis: Unpublished study excluded (Jørgensen 2002)).
Figure 9
Figure 9
Forest plot of comparison: 1 LMWH versus placebo, outcome: 1.3 Proximal DVT.
Figure 10
Figure 10
Forest plot of comparison: 1 LMWH versus placebo, outcome: 1.4 Symptomatic VTE.
Figure 11
Figure 11
Forest plot of comparison: 1 LMWH versus placebo, outcome: 1.5 Bleeding complications.
Analysis 1.1
Analysis 1.1
Comparison 1 LMWH versus placebo, Outcome 1 All VTE.
Analysis 1.2
Analysis 1.2
Comparison 1 LMWH versus placebo, Outcome 2 All DVT.
Analysis 1.3
Analysis 1.3
Comparison 1 LMWH versus placebo, Outcome 3 Proximal DVT.
Analysis 1.4
Analysis 1.4
Comparison 1 LMWH versus placebo, Outcome 4 Symptomatic VTE.
Analysis 1.5
Analysis 1.5
Comparison 1 LMWH versus placebo, Outcome 5 Bleeding complications.
Analysis 1.6
Analysis 1.6
Comparison 1 LMWH versus placebo, Outcome 6 All VTE (Subgroup analysis open only).
Analysis 1.7
Analysis 1.7
Comparison 1 LMWH versus placebo, Outcome 7 All DVT (Subgroup analysis open only).
Analysis 1.8
Analysis 1.8
Comparison 1 LMWH versus placebo, Outcome 8 All VTE (Sensitivity analysis unpublished).
Analysis 1.9
Analysis 1.9
Comparison 1 LMWH versus placebo, Outcome 9 All DVT (Sensitivity analysis unpublished).
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References

References to studies included in this review

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    1. Rasmussen MS, Jørgensen LN, Wille‐Jørgensen P. Prolonged thromboprophylaxis with low molecular weight heparin for abdominal or pelvic surgery. Cochrane Database of Systematic Reviews 2009, Issue 1. [DOI: 10.1002/14651858.CD004318.pub2] - DOI - PubMed

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