Combined intermittent pneumatic leg compression and pharmacological prophylaxis for prevention of venous thromboembolism.

BACKGROUND: It is generally assumed by practitioners and guideline authors that combined modalities (methods of treatment) are more effective than single modalities in preventing venous thromboembolism (VTE), defined as deep vein thrombosis (DVT) or pulmonary embolism (PE), or both. This is the second update of the review first published in 2008. OBJECTIVES: The aim of this review was to assess the efficacy of combined intermittent pneumatic leg compression (IPC) and pharmacological prophylaxis compared to single modalities in preventing VTE. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, and AMED databases, and World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 18 January 2021. We searched the reference lists of relevant articles for additional studies.  SELECTION CRITERIA: We included randomised controlled trials (RCTs) or controlled clinical trials (CCTs) of combined IPC and pharmacological interventions used to prevent VTE compared to either intervention individually. DATA COLLECTION AND ANALYSIS: We independently selected studies, applied Cochrane's risk of bias tool, and extracted data. We resolved disagreements by discussion. We performed fixed-effect model meta-analyses with odds ratios (ORs) and 95% confidence intervals (CIs). We used a random-effects model when there was heterogeneity. We assessed the certainty of the evidence using GRADE. The outcomes of interest were PE, DVT, bleeding and major bleeding. MAIN RESULTS: We included a total of 34 studies involving 14,931 participants, mainly undergoing surgery or admitted with trauma. Twenty-five studies were RCTs (12,672 participants) and nine were CCTs (2259 participants). Overall, the risk of bias was mostly unclear or high. We used GRADE to assess the certainty of the evidence and this was downgraded due to the risk of bias, imprecision or indirectness. The addition of pharmacological prophylaxis to IPC compared with IPC alone reduced the incidence of symptomatic PE from 1.34% (34/2530) in the IPC group to 0.65% (19/2932) in the combined group (OR 0.51, 95% CI 0.29 to 0.91; 19 studies, 5462 participants, low-certainty evidence). The incidence of DVT was 3.81% in the IPC group and 2.03% in the combined group showing a reduced incidence of DVT in favour of the combined group (OR 0.51, 95% CI 0.36 to 0.72; 18 studies, 5394 participants, low-certainty evidence). The addition of pharmacological prophylaxis to IPC, however, increased the risk of any bleeding compared to IPC alone: 0.95% (22/2304) in the IPC group and 5.88% (137/2330) in the combined group (OR 6.02, 95% CI 3.88 to 9.35; 13 studies, 4634 participants, very low-certainty evidence). Major bleeding followed a similar pattern: 0.34% (7/2054) in the IPC group compared to 2.21% (46/2079) in the combined group (OR 5.77, 95% CI 2.81 to 11.83; 12 studies, 4133 participants, very low-certainty evidence). Tests for subgroup differences between orthopaedic and non-orthopaedic surgery participants were not possible for PE incidence as no PE events were reported in the orthopaedic subgroup. No difference was detected between orthopaedic and non-orthopaedic surgery participants for DVT incidence (test for subgroup difference P = 0.19).  The use of combined IPC and pharmacological prophylaxis modalities compared with pharmacological prophylaxis alone reduced the incidence of PE from 1.84% (61/3318) in the pharmacological prophylaxis group to 0.91% (31/3419) in the combined group (OR 0.46, 95% CI 0.30 to 0.71; 15 studies, 6737 participants, low-certainty evidence). The incidence of DVT was 9.28% (288/3105) in the pharmacological prophylaxis group and 5.48% (167/3046) in the combined group (OR 0.38, 95% CI 0.21 to 0.70; 17 studies; 6151 participants, high-certainty evidence). Increased bleeding side effects were not observed for IPC when it was added to anticoagulation (any bleeding: OR 0.87, 95% CI 0.56 to 1.35, 6 studies, 1314 participants, very low-certainty evidence; major bleeding: OR 1.21, 95% CI 0.35 to 4.18, 5 studies, 908 participants, very low-certainty evidence). No difference was detected between the orthopaedic and non-orthopaedic surgery participants for PE incidence (test for subgroup difference P = 0.82) or for DVT incidence (test for subgroup difference P = 0.69). AUTHORS' CONCLUSIONS: Evidence suggests that combining IPC with pharmacological prophylaxis, compared to IPC alone reduces the incidence of both PE and DVT (low-certainty evidence). Combining IPC with pharmacological prophylaxis, compared to pharmacological prophylaxis alone, reduces the incidence of both PE (low-certainty evidence) and DVT (high-certainty evidence). We downgraded due to risk of bias in study methodology and imprecision. Very low-certainty evidence suggests that the addition of pharmacological prophylaxis to IPC increased the risk of bleeding compared to IPC alone, a side effect not observed when IPC is added to pharmacological prophylaxis (very low-certainty evidence), as expected for a physical method of thromboprophylaxis. The certainty of the evidence for bleeding was downgraded to very low due to risk of bias in study methodology, imprecision and indirectness. The results of this update agree with current guideline recommendations, which support the use of combined modalities in hospitalised people (limited to those with trauma or undergoing surgery) at risk of developing VTE. More studies on the role of combined modalities in VTE prevention are needed to provide evidence for specific patient groups and to increase our certainty in the evidence.

Editor's Choice - A Systematic Review and Meta-Analysis of the Efficacy and Safety of Anticoagulation in the Treatment of Venous Thromboembolism in Patients with Cancer.

OBJECTIVE/BACKGROUND: The aim was to review the relative efficacy and safety of anticoagulation for managing venous thromboembolism (VTE) in patients with cancer. METHODS: A systematic review and meta-analysis was carried out. On 17 May 2018 the MEDLINE and Scopus databases were searched for randomised controlled trials (RCTs). Eligible RCTs had to be performed in patients with cancer exclusively or to report results on a subset of patients with cancer. The main study outcomes (efficacy/recurrent VTE and safety/bleeding events) were expressed as risk ratios (RR) with a 95% confidence interval (CI). The quality of evidence was assessed following the GRADE method. RESULTS: Twenty-three RCTs with 6980 patients were identified. Low molecular weight heparins (LMWHs) were more effective than vitamin K antagonists (VKAs) in preventing recurrent VTE (RR 0.58, 95% CI 0.45-0.75) and deep vein thrombosis (RR 0.44, 95% CI 0.29-0.69) but not pulmonary embolism (PE), bleeding, or overall mortality. Direct oral anticoagulants (DOACs) were more effective than VKAs in preventing recurrent VTE (RR 0.65, 95% CI 0.45-0.95) but not DVT, PE, overall mortality, or bleeding. However, anti-Xa DOACs were more effective (RR for VTE 0.64, 95% CI 0.42-0.97) and caused less bleeding than VKAs, although major bleeding was reduced only with DOACs not requiring initial parenteral anticoagulation (RR 0.45, 95% CI 0.21-0.97). In a direct comparison, DOACs were more effective than LMWHs in preventing VTE recurrence (RR 0.64, 95% CI 0.45-0.90) but caused more major bleeding (RR 1.75, 95% CI 1.10-2.77), with no difference in fatal bleeding and overall mortality. Quality of evidence, where sufficient, was mostly moderate or high. CONCLUSION: Compared with VKAs, LMWHs and DOACs are more effective in treating VTE, but the former caused less bleeding. DOACs are more effective than LMWHs in preventing VTE recurrence but may carry a higher risk of major bleeding, pending additional information by ongoing trials.

Optimal Antiplatelet Therapy in Moderate to Severe Asymptomatic and Symptomatic Carotid Stenosis: A Comprehensive Review of the Literature.

OBJECTIVES: Carotid stenosis patients are at risk of vascular events despite antiplatelet therapy. Data on prescribed antiplatelet regimens have not been comprehensively collated from trials to guide optimal therapy in this population. METHODS: This review was conducted in line with the current Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Medline, Ovid, Embase, Web of Science, and Google Scholar from 1988 to 2018 were searched using the search terms "carotid stenosis", "asymptomatic", "symptomatic", "antiplatelet", and "anti-platelet" to identify randomised trials in patients with asymptomatic or symptomatic extracranial moderate-severe carotid stenosis on any form of antiplatelet therapy in which vascular events and pre specified composite outcome events were reported. RESULTS: Twenty-five studies were judged eligible for inclusion. Data from one randomised controlled trial showed no significant difference in benefit with aspirin versus placebo in asymptomatic carotid stenosis, but it is still reasonable to recommend aspirin (81-325 mg daily) for prevention of vascular events in these patients. Low to medium dose aspirin (81-325 mg daily) is superior to higher doses (>650 mg daily) at preventing recurrent vascular events in patients undergoing endarterectomy. Data from endovascular treatment (EVT) trials support peri-procedural treatment of asymptomatic and symptomatic patients with 81-325 mg of aspirin daily. The use of peri-procedural aspirin-clopidogrel in patients undergoing EVT is based on one pilot trial, but appears safe. Short-term aspirin-dipyridamole or aspirin-clopidogrel treatments are equally effective at reducing micro-embolic signals on transcranial Doppler ultrasound in patients with ≥50% symptomatic carotid stenosis. There is insufficient evidence to recommend routine aspirin-clopidogrel combination therapy to reduce the risk of recurrent clinical ischaemic events in patients with symptomatic moderate-severe carotid stenosis. CONCLUSIONS: This comprehensive review outlines an evidence based approach to antiplatelet therapy in carotid stenosis patients. Future trials should randomise such patients to receive different antiplatelet regimens to assess their efficacy and safety and to optimise peri-procedural and long-term preventive treatment in this patient cohort.

Two-stage combined basilic-brachial vein transposition.

In the present report, we describe a two-stage technique of combined basilic and brachial vein transposition. Our patient had a brachial-basilic vein fistula created, but during the second stage for the transposition, a low basilic-brachial vein confluence was found. Instead of abandoning the procedure, the brachial vein was mobilized and transposed to primarily constitute a usable fistula, which subsequently was successfully used for hemodialysis. A detailed description of our technique is provided. Surgeons should be aware of this alternative procedure to maximize fistula creation rates.

Delayed presentation of aortic injury by pedicle screws: report of two cases and review of the literature.

OBJECTIVES: Perforation of the aorta by pedicle screws is a rare but serious complication of spine fixation surgery. This article reviews the clinical presentation and management of this complication. METHODS: Presented are two cases of thoracic aorta perforation by a pedicle screw and a review of the appropriate literature performed using a MEDLINE search. RESULTS: Literature review identified eight additional patients. In most cases, aortic perforation was recognized and managed within 18 months of the spine surgery. Clinical presentation included acute bleeding, necessitating urgent exploration in two patients, and pseudoaneurysm formation in five cases, two of which were infected. Depending on the extent of aortic damage and the presence or absence of infection, management ranged from endovascular grafting, to screw burring with closure of the perforation site, to aortic reconstruction with a tube graft and complete orthopedic hardware removal. Outcome was favorable in all patients who were operated on. CONCLUSIONS: The small number of reported cases indicates either the rarity of this complication or unawareness of its existence. The true incidence of this complication is probably under-reported. Orthopedic and vascular surgeons should be aware of this potentially fatal problem. Prevention remains the best treatment. Once encountered, a variety of techniques are available to manage this complication with reasonable outcome.