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Low molecular weight heparin for prevention of venous thromboembolism in patients with lower-limb immobilization.
Cochrane Database Syst Rev. 2017 08 06; 8:CD006681.CD

Abstract

BACKGROUND

Immobilization of the lower limb is a risk factor for venous thromboembolism (VTE). Low molecular weight heparins (LMWHs) are anticoagulants, which might be used in adult patients with lower-limb immobilization to prevent deep venous thrombosis (DVT) and its complications. This is an update of the review first published in 2008.

OBJECTIVES

To assess the effectiveness of low molecular weight heparin for the prevention of venous thromboembolism in patients with lower-limb immobilization in an ambulatory setting.

SEARCH METHODS

For this update, the Cochrane Vascular Information Specialist searched the Specialised Register, CENTRAL, and three trials registers (April 2017).

SELECTION CRITERIA

Randomized controlled trials (RCTs) and controlled clinical trials (CCTs) that described thromboprophylaxis by means of LMWH compared with no prophylaxis or placebo in adult patients with lower-limb immobilization. Immobilization was by means of a plaster cast or brace.

DATA COLLECTION AND ANALYSIS

Two review authors independently selected trials, assessed risk of bias and extracted data. The review authors contacted the trial authors for additional information if required. Statistical analysis was carried out using Review Manager 5.

MAIN RESULTS

We included eight RCTs that fulfilled our criteria, with a total of 3680 participants. The quality of evidence, according GRADE, varied by outcome and ranged from low to moderate. We found an incidence of DVT ranging from 4.3% to 40% in patients who had a leg injury that had been immobilized in a plaster cast or a brace for at least one week, and who received no prophylaxis, or placebo. This number was significantly lower in patients who received daily subcutaneous injections of LMWH during immobilization, with event rates ranging from 0% to 37% (odds ratio (OR) 0.45, 95% confidence interval (CI) 0.33 to 0.61; with minimal evidence of heterogeneity: I² = 26%, P = 0.23; seven studies; 1676 participants, moderate-quality evidence). Comparable results were seen in the following groups of participants: patients with below-knee casts, conservatively treated patients (non-operated patients), operated patients, patients with fractures, patients with soft-tissue injuries, and patients with distal or proximal thrombosis. No clear differences were found between the LMWH and control groups for pulmonary embolism (OR 0.50, 95% CI 0.17 to 1.47; with no evidence of heterogeneity: I² = 0%, P = 0.56; five studies, 2517 participants; low-quality evidence). The studies also showed less symptomatic VTE in the LMWH groups compared with the control groups (OR 0.40, 95% CI 0.21 to 0.76; with minimal evidence of heterogeneity: I² = 16%, P = 0.31; six studies; 2924 participants; low-quality evidence). One death was reported in the included studies, but no deaths due to pulmonary embolism were reported. Complications of major adverse events were rare, with minor bleeding the main adverse events reported.

AUTHORS' CONCLUSIONS

Moderate-quality evidence showed that the use of LMWH in outpatients reduced DVT when immobilization of the lower limb was required, when compared with no prophylaxis or placebo. The quality of the evidence was reduced to moderate because of risk of selection and attrition bias in the included studies. Low-quality evidence showed no clear differences in PE between the LMWH and control groups, but less symptomatic VTE in the LMWH groups. The quality of the evidence was downgraded due to risk of bias and imprecision.

Authors+Show Affiliations

Department of Surgery, VieCuri Medical Centre of Northern Limburg, Venlo, Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't
Review
Systematic Review

Language

eng

PubMed ID

28780771

Citation

Zee, Aniek Ag, et al. "Low Molecular Weight Heparin for Prevention of Venous Thromboembolism in Patients With Lower-limb Immobilization." The Cochrane Database of Systematic Reviews, vol. 8, 2017, p. CD006681.
Zee AA, van Lieshout K, van der Heide M, et al. Low molecular weight heparin for prevention of venous thromboembolism in patients with lower-limb immobilization. Cochrane Database Syst Rev. 2017;8:CD006681.
Zee, A. A., van Lieshout, K., van der Heide, M., Janssen, L., & Janzing, H. M. (2017). Low molecular weight heparin for prevention of venous thromboembolism in patients with lower-limb immobilization. The Cochrane Database of Systematic Reviews, 8, CD006681. https://doi.org/10.1002/14651858.CD006681.pub4
Zee AA, et al. Low Molecular Weight Heparin for Prevention of Venous Thromboembolism in Patients With Lower-limb Immobilization. Cochrane Database Syst Rev. 2017 08 6;8:CD006681. PubMed PMID: 28780771.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Low molecular weight heparin for prevention of venous thromboembolism in patients with lower-limb immobilization. AU - Zee,Aniek Ag, AU - van Lieshout,Kelly, AU - van der Heide,Maaike, AU - Janssen,Loes, AU - Janzing,Heinrich Mj, Y1 - 2017/08/06/ PY - 2017/8/7/pubmed PY - 2017/9/20/medline PY - 2017/8/7/entrez SP - CD006681 EP - CD006681 JF - The Cochrane database of systematic reviews JO - Cochrane Database Syst Rev VL - 8 N2 - BACKGROUND: Immobilization of the lower limb is a risk factor for venous thromboembolism (VTE). Low molecular weight heparins (LMWHs) are anticoagulants, which might be used in adult patients with lower-limb immobilization to prevent deep venous thrombosis (DVT) and its complications. This is an update of the review first published in 2008. OBJECTIVES: To assess the effectiveness of low molecular weight heparin for the prevention of venous thromboembolism in patients with lower-limb immobilization in an ambulatory setting. SEARCH METHODS: For this update, the Cochrane Vascular Information Specialist searched the Specialised Register, CENTRAL, and three trials registers (April 2017). SELECTION CRITERIA: Randomized controlled trials (RCTs) and controlled clinical trials (CCTs) that described thromboprophylaxis by means of LMWH compared with no prophylaxis or placebo in adult patients with lower-limb immobilization. Immobilization was by means of a plaster cast or brace. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials, assessed risk of bias and extracted data. The review authors contacted the trial authors for additional information if required. Statistical analysis was carried out using Review Manager 5. MAIN RESULTS: We included eight RCTs that fulfilled our criteria, with a total of 3680 participants. The quality of evidence, according GRADE, varied by outcome and ranged from low to moderate. We found an incidence of DVT ranging from 4.3% to 40% in patients who had a leg injury that had been immobilized in a plaster cast or a brace for at least one week, and who received no prophylaxis, or placebo. This number was significantly lower in patients who received daily subcutaneous injections of LMWH during immobilization, with event rates ranging from 0% to 37% (odds ratio (OR) 0.45, 95% confidence interval (CI) 0.33 to 0.61; with minimal evidence of heterogeneity: I² = 26%, P = 0.23; seven studies; 1676 participants, moderate-quality evidence). Comparable results were seen in the following groups of participants: patients with below-knee casts, conservatively treated patients (non-operated patients), operated patients, patients with fractures, patients with soft-tissue injuries, and patients with distal or proximal thrombosis. No clear differences were found between the LMWH and control groups for pulmonary embolism (OR 0.50, 95% CI 0.17 to 1.47; with no evidence of heterogeneity: I² = 0%, P = 0.56; five studies, 2517 participants; low-quality evidence). The studies also showed less symptomatic VTE in the LMWH groups compared with the control groups (OR 0.40, 95% CI 0.21 to 0.76; with minimal evidence of heterogeneity: I² = 16%, P = 0.31; six studies; 2924 participants; low-quality evidence). One death was reported in the included studies, but no deaths due to pulmonary embolism were reported. Complications of major adverse events were rare, with minor bleeding the main adverse events reported. AUTHORS' CONCLUSIONS: Moderate-quality evidence showed that the use of LMWH in outpatients reduced DVT when immobilization of the lower limb was required, when compared with no prophylaxis or placebo. The quality of the evidence was reduced to moderate because of risk of selection and attrition bias in the included studies. Low-quality evidence showed no clear differences in PE between the LMWH and control groups, but less symptomatic VTE in the LMWH groups. The quality of the evidence was downgraded due to risk of bias and imprecision. SN - 1469-493X UR - https://www.unboundmedicine.com/medline/citation/28780771/Low_molecular_weight_heparin_for_prevention_of_venous_thromboembolism_in_patients_with_lower_limb_immobilization_ L2 - https://doi.org/10.1002/14651858.CD006681.pub4 DB - PRIME DP - Unbound Medicine ER -