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Pharmacological thromboprophylaxis to prevent venous thromboembolism in patients with temporary lower limb immobilization after injury: systematic review and network meta-analysis.

ABSTRACT: BACKGROUND:Thromboprophylaxis has the potential to reduce venous thromboembolism (VTE) following lower limb immobilization resulting from injury. OBJECTIVES:We aimed to estimate the effectiveness of thromboprophylaxis, compare different agents, and identify any factors associated with effectiveness. METHODS:We undertook a systematic review and network meta-analysis (NMA) of randomized trials reporting VTE or bleeding outcomes that compared thromboprophylactic agents with each other or to no pharmacological prophylaxis, for this indication. An NMA was undertaken for each outcome or agent used, and a series of study-level network meta-regressions examined whether population characteristics, type of injury, treatment of injury, or duration of thromboprophylaxis were associated with treatment effect. RESULTS:Data from 6857 participants across 13 randomized trials showed that, compared with no treatment, low molecular weight heparin (LMWH) reduced the risk of any VTE (odds ratio [OR]: 0.52; 95% credible interval [CrI]: 0.37-0.71), clinically detected deep vein thrombosis (DVT) (OR: 0.39; 95% CrI: 0.12-0.94) and pulmonary embolism (PE) (OR: 0.16; 95% CrI: 0.01-0.74), whereas fondaparinux reduced the risk of any VTE (OR: 0.13; 95% CrI: 0.05-0.30) and clinically detected DVT (OR: 0.10; 95% CrI: 0.01-0.86), with inconclusive results for PE (OR: 0.40; 95% CrI: 0.01-7.53). CONCLUSIONS:Thromboprophylaxis with either fondaparinux or LMWH appears to reduce the odds of both asymptomatic and clinically detected VTE in people with temporary lower limb immobilization following an injury. Treatment effects vary by outcome and are not always conclusive. We were unable to identify any treatment effect modifiers other than thromboprophylactic agent used.

SUBMITTER: Horner D

PROVIDER: S-EPMC7028118 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Pharmacological thromboprophylaxis to prevent venous thromboembolism in patients with temporary lower limb immobilization after injury: systematic review and network meta-analysis.

Horner Daniel D Stevens John W JW Pandor Abdullah A Nokes Tim T Keenan Jonathan J de Wit Kerstin K Goodacre Steve S

Journal of thrombosis and haemostasis : JTH 20191201 2

<h4>Background</h4>Thromboprophylaxis has the potential to reduce venous thromboembolism (VTE) following lower limb immobilization resulting from injury.<h4>Objectives</h4>We aimed to estimate the effectiveness of thromboprophylaxis, compare different agents, and identify any factors associated with effectiveness.<h4>Methods</h4>We undertook a systematic review and network meta-analysis (NMA) of randomized trials reporting VTE or bleeding outcomes that compared thromboprophylactic agents with ea ...[more]

PMID: 31654551

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Project description:Essentials Thromboprophylaxis after lower limb injury is often based on complex risk stratification. Our systematic review identified variables predicting venous thromboembolism (VTE) in this group. Age and injury type were commonly reported to increase the odds of VTE (odds ratio 1.5-3.48). We found limited evidence to support the use of other risk factors within prediction models. SUMMARY: Background Patients immobilized after lower limb injury are at risk of venous thromboembolism (VTE). There is international variation in the use of thromboprophylaxis for such patients. Risk-based strategies have been adopted to aid decision making in many settings. The accuracy of these strategies is unclear. Objectives A systematic review was undertaken to identify all individual patient-identifiable risk factors linked to any VTE outcome following lower limb immobilization. Methods Several electronic databases were searched from inception to May 2017. Any studies that included a measurement of VTE as a patient outcome in adults requiring temporary immobilization (e.g. leg cast or brace in an ambulatory setting) for an isolated lower limb injury and reported risk factor variables were included. Descriptive statistics and thematic analysis were used to synthesize the evidence. Results Our database search returned 4771 citations, of which 15 studies reporting outcome data on 80 678 patients were eligible for analysis. Risk-factor associations were reported through regression analyses, non-parametric tests and descriptive statistics. All studies were assessed as at moderate or serious risk of bias using the ROBINS-I risk of bias tool. Advancing age and injury type were the only individual risk factors demonstrating a reproducible association with increased symptomatic and/or asymptomatic VTE rates. Several risk factors currently used in scoring tools did not appear to be robustly evaluated for subsequent association with VTE within these studies. Conclusions Clinicians should be aware of the limited evidence to support individual risk factors in guiding thromboprophylaxis use for this patient cohort.

Project description:BackgroundImmobilization 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.ObjectivesTo 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 methodsFor this update, the Cochrane Vascular Information Specialist searched the Specialised Register, CENTRAL, and three trials registers (April 2017).Selection criteriaRandomized 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 analysisTwo 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 resultsWe 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' conclusionsModerate-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.

Dataset Information

Pharmacological thromboprophylaxis to prevent venous thromboembolism in patients with temporary lower limb immobilization after injury: systematic review and network meta-analysis.

Publications

Pharmacological thromboprophylaxis to prevent venous thromboembolism in patients with temporary lower limb immobilization after injury: systematic review and network meta-analysis.

Similar Datasets

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