Aspirin or Low-Molecular-Weight Heparin for Thromboprophylaxis after a Fracture.

BACKGROUND: Clinical guidelines recommend low-molecular-weight heparin for thromboprophylaxis in patients with fractures, but trials of its effectiveness as compared with aspirin are lacking. METHODS: In this pragmatic, multicenter, randomized, noninferiority trial, we enrolled patients 18 years of age or older who had a fracture of an extremity (anywhere from hip to midfoot or shoulder to wrist) that had been treated operatively or who had any pelvic or acetabular fracture. Patients were randomly assigned to receive low-molecular-weight heparin (enoxaparin) at a dose of 30 mg twice daily or aspirin at a dose of 81 mg twice daily while they were in the hospital. After hospital discharge, the patients continued to receive thromboprophylaxis according to the clinical protocols of each hospital. The primary outcome was death from any cause at 90 days. Secondary outcomes were nonfatal pulmonary embolism, deep-vein thrombosis, and bleeding complications. RESULTS: A total of 12,211 patients were randomly assigned to receive aspirin (6101 patients) or low-molecular-weight heparin (6110 patients). Patients had a mean (±SD) age of 44.6±17.8 years, 0.7% had a history of venous thromboembolism, and 2.5% had a history of cancer. Patients received a mean of 8.8±10.6 in-hospital thromboprophylaxis doses and were prescribed a median 21-day supply of thromboprophylaxis at discharge. Death occurred in 47 patients (0.78%) in the aspirin group and in 45 patients (0.73%) in the low-molecular-weight-heparin group (difference, 0.05 percentage points; 96.2% confidence interval, -0.27 to 0.38; P<0.001 for a noninferiority margin of 0.75 percentage points). Deep-vein thrombosis occurred in 2.51% of patients in the aspirin group and 1.71% in the low-molecular-weight-heparin group (difference, 0.80 percentage points; 95% CI, 0.28 to 1.31). The incidence of pulmonary embolism (1.49% in each group), bleeding complications, and other serious adverse events were similar in the two groups. CONCLUSIONS: In patients with extremity fractures that had been treated operatively or with any pelvic or acetabular fracture, thromboprophylaxis with aspirin was noninferior to low-molecular-weight heparin in preventing death and was associated with low incidences of deep-vein thrombosis and pulmonary embolism and low 90-day mortality. (Funded by the Patient-Centered Outcomes Research Institute; PREVENT CLOT ClinicalTrials.gov number, NCT02984384.).

An Updated Systematic Review and Meta-analysis of the Impact of Graduated Compression Stockings in Addition to Pharmacological Thromboprophylaxis for Prevention of Venous Thromboembolism in Surgical Inpatients.

OBJECTIVE: To compare the rate of venous thromboembolism (VTE) in surgical inpatients with pharmacological thromboprophylaxis and additional graduated compression stockings (GCSs) versus pharmacological thromboprophylaxis alone. BACKGROUND: Surgical inpatients have elevated VTE risk; recent studies cast doubt on whether GCS confers additional protection against VTE, compared with pharmacological thromboprophylaxis alone. METHODS: The review followed "Preferred Reporting Items for Systematic Reviews and Meta-analyses" guidelines using a registered protocol (CRD42017062655). The MEDLINE and Embase databases were searched up to November 2022. Randomized trials reporting VTE rate after surgical procedures, utilizing pharmacological thromboprophylaxis, with or without GCS, were included. The rates of deep venous thrombosis (DVT), pulmonary embolism, and VTE-related mortality were pooled through fixed and random effects. RESULTS: In a head-to-head meta-analysis, the risk of DVT for GCS and pharmacological thromboprophylaxis was 0.85 (95% CI: 0.54-1.36) versus for pharmacological thromboprophylaxis alone (2 studies, 70 events, 2653 participants). The risk of DVT in pooled trial arms for GCS and pharmacological thromboprophylaxis was 0.54 (95% CI: 0.23-1.25) versus pharmacological thromboprophylaxis alone (33 trial arms, 1228 events, 14,108 participants). The risk of pulmonary embolism for GCS and pharmacological prophylaxis versus pharmacological prophylaxis alone was 0.71 (95% CI: 0.0-30.0) (27 trial arms, 32 events, 11,472 participants). There were no between-group differences in VTE-related mortality (27 trial arms, 3 events, 12,982 participants). CONCLUSIONS: Evidence from head-to-head meta-analysis and pooled trial arms demonstrates no additional benefit for GCS in preventing VTE and VTE-related mortality. GCS confer a risk of skin complications and an economic burden; current evidence does not support their use for surgical inpatients.

Structured benefit-risk assessment for enoxaparin, in the context of its label extension, for the extended treatment of deep vein thrombosis and pulmonary embolism, and prevention of its recurrence in patients with active cancer.

PURPOSE: Guidelines recommend low-molecular-weight heparins (LMWHs) for patients with cancer-associated thrombosis. However, until recently, only dalteparin and tinzaparin were approved in the European Economic Area (EEA) for these patients. This study compares the benefit-risk profile of enoxaparin with dalteparin and tinzaparin for the extended treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrence in adult patients with active cancer. METHODS: A semi-quantitative structured benefit-risk assessment was conducted for the label-extension application of enoxaparin based on the benefit-risk action team descriptive framework: define decision context; determine key benefit and risk outcomes; identify data sources; extract data; interpret results. RESULTS: The key benefits were defined as reduced all-cause mortality and venous thromboembolism (VTE) recurrence (including symptomatic DVT, fatal PE or non-fatal PE); the key risks were major and non-major bleeding of clinical significance, and heparin-induced thrombocytopenia (HIT). Enoxaparin demonstrated comparable effects for the reduction of VTE recurrence and all-cause mortality versus other EEA-approved LMWHs (dalteparin, tinzaparin). There was no evidence of a significant difference between enoxaparin and the comparator groups with regard to incidence of major and non-major bleeding. The data on HIT were too limited to assess the difference between the two groups. CONCLUSIONS: The assessment demonstrated a favourable benefit-risk profile for enoxaparin similar to that of other EEA-approved LMWHs for the treatment of DVT and PE and the prevention of recurrence in patients with active cancer and thus supported the label-extension approval.

A change in strategy for filter choice leads to improved filter retrieval rates.

OBJECTIVE: To assess whether a new strategy for the choice of inferior vena cava filter placed would improve filter retrieval rates at our institution. METHODS: Consecutive patients who underwent retrievable filter placement for temporary embolic protection between January 2021 and January 2023 were considered for study inclusion. Risk factors for nonretrieval of short-term filters were identified in patients receiving filters between January 2021 and January 2022 (prestrategy group). For patients treated between February 2022 and January 2023 (poststrategy group), a long-term filter was recommended for those with these risk factors, and a short-term filter was recommended for those without these risk factors. RESULTS: The study population included 303 patients (prestrategy group, n = 154; poststrategy group, n = 149). Long-term immobilization (odds ratio [OR] = 38.000; 95% confidence interval [CI]: 6.858-210.564), active cancer (OR = 17.643; 95% CI: 5.462-56.993), and venous thromboembolism detected in the intensive care unit (OR = 28.500; 95% CI: 7.419-109.477) were identified as independent risk factors for nonretrieval of short-term filters. The total retrieval rate was significantly higher in the poststrategy group (87.2%) than in the prestrategy group (72.7%; P = 0.002); the short-term filter retrieval rate was also significantly higher in the poststrategy group (84.5%) than in the prestrategy group (68.5%; P < 0.001). CONCLUSION: The proposed strategy for filter choice based on risk factors for short-term filter nonretrieval can accurately identify patients who need long-term filter placement while also increasing the retrieval rates for both short-term filters retrieval rates and overall retrieval rates.

Risk stratification-based thromboprophylaxis does not affect mortality after fast-track hip and knee arthroplasty.

BACKGROUND AND PURPOSE: Use of thromboprophylaxis effectively prevents pulmonary embolism (PE) and deaths after total hip and knee arthroplasty (THA and TKA). The optimum length of thromboprophylaxis is not known and has traditionally been based on the type of operation. Nowadays, a more individualized approach is preferred. This study analyzed if risk stratification-based planning of thromboprophylaxis has an association with the all-cause mortality after fast-track THA and TKA. PATIENTS AND METHODS: We compared fast-track THAs and TKAs operated between 2015-2016 and 2020-2021. Between 2015 and 2016, all patients received a routine length of thromboprophylaxis. From 2020 onwards, thromboprophylaxis was planned by risk stratification, and patients at low risk for venous thromboembolism received thromboprophylaxis only during hospitalization. All causes of death within 90 days of surgery were identified and the incidence of mortality was calculated. Mortality rates between the two periods were then compared. RESULTS: Between 2015 and 2016, 3192 arthroplasties were performed. A total of eight deaths occurred within 90 days of surgery, yielding an incidence of all-cause mortality of 0.3% (95% CI 0.1-0.5). Between 2020 and 2021, a total of 3713 arthroplasties were performed to patients who received risk stratification-based thromboprophylaxis. Thirteen of these patients died within 90 days of surgery, yielding an all-cause mortality incidence of 0.4% (95% CI 0.2-0.6). Cardiovascular diseases were the main cause of death during both study periods. None of the deaths were caused by PEs. INTERPRETATION: Risk stratification-based thromboprophylaxis was not associated with increased all-cause mortality within 90 days of fast-track THA and TKA.

[Prevention and treatment of venous thromboembolic complications in orthopedic patients]. / Kompleksnaya profilaktika i lechenie venoznykh tromboembolicheskikh oslozhnenii u patsientov ortopedicheskogo profilya.

OBJECTIVE: To analyze the comprehensive program for prevention of thromboembolic complications in orthopedic patients. MATERIAL AND METHODS: We have analyzed thromboembolic complications in orthopedic patients after surgeries on large joints over the past 5 years (2018-2022). CONCLUSION: A comprehensive approach to prevention and treatment of thromboembolic complications including ultrasound, early surgical prevention of pulmonary embolism can significantly improve postoperative outcomes after joint replacement surgery. Vacuum aspiration retrograde thrombectomy is effective, feasible and safe for acute ilio-femoral venous thrombosis reducing hospital-stay (p=0.0124) and restoring vein patency. Widespread thromboembolic complications, especially for pulmonary embolism in 2022, are likely due to a new coronavirus infection and require careful screening of patients with risk factors with appropriate preventive antithrombotic therapy.

Efficacy and Safety of Anti-Xa-Guided Versus Fixed Dosing of Low Molecular Weight Heparin for Prevention of Venous Thromboembolism in Trauma Patients: A Systematic Review and Meta-Analysis.

PURPOSE: Trauma patients are at high risk of venous thromboembolism (VTE). We summarize the comparative efficacy and safety of anti-Xa-guided versus fixed dosing for low molecular weight heparin (LMWH) for the prevention of VTE in adult trauma patients. METHODS: We searched Medline and Embase from inception through June 1, 2022. We included randomized controlled trials or observational studies comparing anti-Xa-guided versus fixed dosing of LMWH for thromboprophylaxis in adult trauma patients. We incorporated primary data from 2 large observational cohorts. We pooled effect estimates using a random-effects model. We assessed risk of bias using the ROBINS-I tool for observational studies and assessed certainty of findings using GRADE methodology. RESULTS: We included 15 observational studies involving 10,348 patients. No randomized controlled trials were identified. determined that, compared to fixed LMWH dosing, anti-Xa-guided dosing may reduce deep vein thrombosis [adjusted odds ratio (aOR); 0.52, 95% CI: 0.40-0.69], pulmonary embolism (aOR: 0.48, 95% CI: 0.30-0.78) or any VTE (aOR: 0.54, 95% CI: 0.42-0.69), though all estimates are based on low certainty evidence. There was an uncertain effect on mortality (aOR: 1.06, 95% CI: 0.85-1.32) and bleeding events (aOR: 0.84, 95% CI: 0.50-1.39), limited by serious imprecision. We used several sensitivity and subgroup analyses to confirm the validity of our assumptions. CONCLUSION: Anti-Xa-guided dosing may be more effective than fixed dosing for prevention of deep vein thrombosis, pulmonary embolism, and VTE for adult trauma patients. These promising findings justify the need for a high-quality randomized study with the potential to deliver practice changing results.

Intermediate-dose versus low-dose low-molecular-weight heparin in pregnant and post-partum women with a history of venous thromboembolism (Highlow study): an open-label, multicentre, randomised, controlled trial.

BACKGROUND: Pregnancy-related venous thromboembolism is a leading cause of maternal morbidity and mortality, and thromboprophylaxis is indicated in pregnant and post-partum women with a history of venous thromboembolism. The optimal dose of low-molecular-weight heparin to prevent recurrent venous thromboembolism in pregnancy and the post-partum period is uncertain. METHODS: In this open-label, randomised, controlled trial (Highlow), pregnant women with a history of venous thromboembolism were recruited from 70 hospitals in nine countries (the Netherlands, France, Ireland, Belgium, Norway, Denmark, Canada, the USA, and Russia). Women were eligible if they were aged 18 years or older with a history of objectively confirmed venous thromboembolism, and with a gestational age of 14 weeks or less. Eligible women were randomly assigned (1:1), before 14 weeks of gestational age, using a web-based system and permuted block randomisation (block size of six), stratified by centre, to either weight-adjusted intermediate-dose or fixed low-dose low-molecular-weight heparin subcutaneously once daily until 6 weeks post partum. The primary efficacy outcome was objectively confirmed venous thromboembolism (ie, deep-vein thrombosis, pulmonary embolism, or unusual site venous thrombosis), as determined by an independent central adjudication committee, in the intention-to-treat (ITT) population (ie, all women randomly assigned to treatment). The primary safety outcome was major bleeding which included antepartum, early post-partum (within 24 h after delivery), and late post-partum major bleeding (24 h or longer after delivery until 6 weeks post partum), assessed in all women who received at least one dose of assigned treatment and had a known end of treatment date. This study is registered with ClinicalTrials.gov, NCT01828697, and is now complete. FINDINGS: Between April 24, 2013, and Oct 31, 2020, 1339 pregnant women were screened for eligibility, of whom 1110 were randomly assigned to weight-adjusted intermediate-dose (n=555) or fixed low-dose (n=555) low-molecular-weight heparin (ITT population). Venous thromboembolism occurred in 11 (2%) of 555 women in the weight-adjusted intermediate-dose group and in 16 (3%) of 555 in the fixed low-dose group (relative risk [RR] 0·69 [95% CI 0·32-1·47]; p=0·33). Venous thromboembolism occurred antepartum in five (1%) women in the intermediate-dose group and in five (1%) women in the low-dose group, and post partum in six (1%) women and 11 (2%) women. On-treatment major bleeding in the safety population (N=1045) occurred in 23 (4%) of 520 women in the intermediate-dose group and in 20 (4%) of 525 in the low-dose group (RR 1·16 [95% CI 0·65-2·09]). INTERPRETATION: In women with a history of venous thromboembolism, weight-adjusted intermediate-dose low-molecular-weight heparin during the combined antepartum and post-partum periods was not associated with a lower risk of recurrence than fixed low-dose low-molecular-weight heparin. These results indicate that low-dose low-molecular-weight heparin for thromboprophylaxis during pregnancy is the appropriate dose for the prevention of pregnancy-related recurrent venous thromboembolism. FUNDING: French Ministry of Health, Health Research Board Ireland, GSK/Aspen, and Pfizer.

Rivaroxaban or Enoxaparin in Nonmajor Orthopedic Surgery.

BACKGROUND: Nonmajor orthopedic surgery of the lower limbs that results in transient reduced mobility places patients at risk for venous thromboembolism. Rivaroxaban may be noninferior to enoxaparin with regard to the prevention of major venous thromboembolism in these patients. METHODS: In this international, parallel-group, randomized, double-blind, noninferiority trial, we randomly assigned adult patients undergoing lower-limb nonmajor orthopedic surgery who were considered to be at risk for venous thromboembolism on the basis of the investigator's judgment to receive either rivaroxaban or enoxaparin. The primary efficacy outcome of major venous thromboembolism was a composite of symptomatic distal or proximal deep-vein thrombosis, pulmonary embolism, or venous thromboembolism-related death during the treatment period or asymptomatic proximal deep-vein thrombosis at the end of treatment. A test for superiority was planned if rivaroxaban proved to be noninferior to enoxaparin. For all outcomes, multiple imputation was used to account for missing data. Prespecified safety outcomes included major bleeding (fatal, critical, or clinically overt bleeding or bleeding at the surgical site leading to intervention) and nonmajor clinically relevant bleeding. RESULTS: A total of 3604 patients underwent randomization; 1809 patients were assigned to receive rivaroxaban, and 1795 to receive enoxaparin. Major venous thromboembolism occurred in 4 of 1661 patients (0.2%) in the rivaroxaban group and in 18 of 1640 patients (1.1%) in the enoxaparin group (risk ratio with multiple imputation, 0.25; 95% confidence interval, 0.09 to 0.75; P<0.001 for noninferiority; P = 0.01 for superiority). The incidence of bleeding did not differ significantly between the rivaroxaban group and the enoxaparin group (1.1% and 1.0%, respectively, for major bleeding or nonmajor clinically relevant bleeding; 0.6% and 0.7%, respectively, for major bleeding). CONCLUSIONS: Rivaroxaban was more effective than enoxaparin in the prevention of venous thromboembolic events during a period of immobilization after nonmajor orthopedic surgery of the lower limbs. (Funded by Centre Hospitalier Universitaire de Saint-Etienne and Bayer; PRONOMOS ClinicalTrials.gov number, NCT02401594.).

Apixaban for the Treatment of Venous Thromboembolism Associated with Cancer.

BACKGROUND: Recent guidelines recommend consideration of the use of oral edoxaban or rivaroxaban for the treatment of venous thromboembolism in patients with cancer. However, the benefit of these oral agents is limited by the increased risk of bleeding associated with their use. METHODS: This was a multinational, randomized, investigator-initiated, open-label, noninferiority trial with blinded central outcome adjudication. We randomly assigned consecutive patients with cancer who had symptomatic or incidental acute proximal deep-vein thrombosis or pulmonary embolism to receive oral apixaban (at a dose of 10 mg twice daily for the first 7 days, followed by 5 mg twice daily) or subcutaneous dalteparin (at a dose of 200 IU per kilogram of body weight once daily for the first month, followed by 150 IU per kilogram once daily). The treatments were administered for 6 months. The primary outcome was objectively confirmed recurrent venous thromboembolism during the trial period. The principal safety outcome was major bleeding. RESULTS: Recurrent venous thromboembolism occurred in 32 of 576 patients (5.6%) in the apixaban group and in 46 of 579 patients (7.9%) in the dalteparin group (hazard ratio, 0.63; 95% confidence interval [CI], 0.37 to 1.07; P<0.001 for noninferiority). Major bleeding occurred in 22 patients (3.8%) in the apixaban group and in 23 patients (4.0%) in the dalteparin group (hazard ratio, 0.82; 95% CI, 0.40 to 1.69; P = 0.60). CONCLUSIONS: Oral apixaban was noninferior to subcutaneous dalteparin for the treatment of cancer-associated venous thromboembolism without an increased risk of major bleeding. (Funded by the Bristol-Myers Squibb-Pfizer Alliance; Caravaggio ClinicalTrials.gov number, NCT03045406.).

Risk of venous thromboembolism in patients undergoing gastric cancer surgery: a systematic review and meta-analysis.

BACKGROUND: Venous thromboembolism (VTE) is a common postoperative complication in patients undergoing surgery for gastric cancer (GC). Although VTE incidence may vary among cancers, guidelines rarely stratify preventive methods for postoperative VTE by cancer type. The risk of VTE in patients undergoing surgery for GC remains unclear. METHODS: A systematic review and meta-analysis was undertaken to determine the risk of VTE after GC surgery and discuss the clinical value of pharmacological thromboprophylaxis in these cases. Medline, Embase, Web of Science, and Cochrane Library databases were searched for articles published from their inception to September 2022. RESULTS: Overall, 13 studies (111,936 patients) were included. The overall 1-month incidence of VTE, deep vein thrombosis (DVT), and pulmonary embolism (PE) after GC surgery was 1.8% (95% CI, 0.8-3.1%; I²=98.5%), 1.2% (95% CI, 0.5-2.1%; I²=96.1%), and 0.4% (95% CI, 0.1-1.1%; I²=96.3%), respectively. The prevalence of postoperative VTE was comparable between Asian and Western populations (1.8% vs. 1.8%; P > 0.05). Compared with mechanical prophylaxis alone, mechanical plus pharmacological prophylaxis was associated with a significantly lower 1-month rate of postoperative VTE and DVT (0.6% vs. 2.9% and 0.6% vs. 2.8%, respectively; all P < 0.05), but not PE (P > 0.05). The 1-month postoperative incidence of VTE was not significantly different between laparoscopic and open surgery (1.8% vs. 4.3%, P > 0.05). CONCLUSION: Patients undergoing GC surgery do not have a high risk of VTE. The incidence of VTE after GC surgery is not significantly different between Eastern and Western patients. Mechanical plus pharmacological prophylaxis is more effective than mechanical prophylaxis alone in postoperative VTE prevention. The VTE risk is comparable between open and laparoscopic surgery for GC.

Angioembolization in Severe Pelvic Trauma is Associated with Venous Thromboembolism.

INTRODUCTION: Management of hemorrhage from pelvic fractures is complex and requires multidisciplinary attention. Pelvic angioembolization (AE) has become a key intervention to aid in obtaining definitive hemorrhage control. We hypothesized that pelvic AE would be associated with an increased risk of venous thromboembolism (VTE). METHODS: All adults (age >16) with a severe pelvic fracture (Abbreviated Injury Scale ≥ 4) secondary to a blunt traumatic mechanism in the 2017-2019 American College of Surgeons Trauma Quality Improvement Program database were included. Patients who did not receive VTE prophylaxis during their admission were excluded. Patients who underwent pelvic AE during the first 24 h of admission were compared to those who did not using propensity score matching. Matching was performed based on patient demographics, admission physiology, comorbidities, injury severity, associated injuries, other hemorrhage control procedures, and VTE prophylaxis type, and time to initiation of VTE prophylaxis. The rates of VTE (deep vein thrombosis and pulmonary embolism) were compared between the matched groups. RESULTS: Of 72,985 patients with a severe blunt pelvic fracture, 1887 (2.6%) underwent pelvic AE during the first 24 h of admission versus 71,098 (97.4%) who did not. Pelvic AE patients had a higher median Injury Severity Score and more often required other hemorrhage control procedures, with laparotomy being most common (24.7%). The median time to initiation of VTE prophylaxis in pelvic AE versus no pelvic AE patients was 60.1 h (interquartile range = 36.6-98.6) versus 27.7 h (interquartile range = 13.9-52.4), respectively. After propensity score matching, pelvic AE patients were more likely to develop VTE compared to no pelvic AE patients (11.8% versus 9.5%, P = 0.03). CONCLUSIONS: Pelvic AE for control of hemorrhage from severe pelvic fractures is associated with an increased risk of in-hospital VTE. Patients who undergo pelvic AE are especially high risk for VTE and should be started as early as safely possible on VTE prophylaxis.

Predicting the Safety and Effectiveness of Inferior Vena Cava Filters (PRESERVE): Outcomes at 12 months.

OBJECTIVE: To determine the safety and effectiveness of vena cava filters (VCFs). METHODS: A total of 1429 participants (62.7 ± 14.7 years old; 762 [53.3% male]) consented to enroll in this prospective, nonrandomized study at 54 sites in the United States between October 10, 2015, and March 31, 2019. They were evaluated at baseline and at 3, 6, 12, 18, and 24 months following VCF implantation. Participants whose VCFs were removed were followed for 1 month after retrieval. Follow-up was performed at 3, 12, and 24 months. Predetermined composite primary safety (freedom from perioperative serious adverse events [AEs] and from clinically significant perforation, VCF embolization, caval thrombotic occlusion, and/or new deep vein thrombosis [DVT] within 12-months) and effectiveness (composite comprising procedural and technical success and freedom from new symptomatic pulmonary embolism [PE] confirmed by imaging at 12-months in situ or 1 month postretrieval) end points were assessed. RESULTS: VCFs were implanted in 1421 patients. Of these, 1019 (71.7%) had current DVT and/or PE. Anticoagulation therapy was contraindicated or had failed in 1159 (81.6%). One hundred twenty-six (8.9%) VCFs were prophylactic. Mean and median follow-up for the entire population and for those whose VCFs were not removed was 243.5 ± 243.3 days and 138 days and 332.6 ± 290 days and 235 days, respectively. VCFs were removed from 632 (44.5%) patients at a mean of 101.5 ± 72.2 days and median 86.3 days following implantation. The primary safety end point and primary effectiveness end point were both achieved. Procedural AEs were uncommon and usually minor, but one patient died during attempted VCF removal. Excluding strut perforation greater than 5 mm, which was demonstrated on 31 of 201 (15.4%) patients' computed tomography scans available to the core laboratory, and of which only 3 (0.2%) were deemed clinically significant by the site investigators, VCF-related AEs were rare (7 of 1421, 0.5%). Postfilter, venous thromboembolic events (none fatal) occurred in 93 patients (6.5%), including DVT (80 events in 74 patients [5.2%]), PE (23 events in 23 patients [1.6%]), and/or caval thrombotic occlusions (15 events in 15 patients [1.1%]). No PE occurred in patients following prophylactic placement. CONCLUSIONS: Implantation of VCFs in patients with venous thromboembolism was associated with few AEs and with a low incidence of clinically significant PEs.

Prevention of venous thromboembolism in right heart-sided electrophysiological procedures: results of an European Heart Rhythm Association survey.

Limited data are available regarding venous thromboembolism (VTE), specifically deep vein thrombosis (DVT) and pulmonary embolism (PE), following right-sided ablations and electrophysiological (EP) studies. Compared to left-sided procedures, no guidelines on antithrombotic management strategies for the prevention of DVT and PE are available. The main purpose of the present European Heart Rhythm Association (EHRA) survey is to report the current management of right-sided EP procedures, focusing on anticoagulation and prevention of VTE. An online survey was conducted using the EHRA infrastructure. A total of 244 participants answered a 19-items questionnaire on the periprocedural management of EP studies and right-sided catheter ablations. The right femoral vein is the most common access for EP studies and right-sided procedures. An ultrasound-guided approach is employed by more than 2/3 of respondents. Intravenous heparin is not commonly given by the majority of participants. About 1/3 of participants (34%) routinely prescribe VTE prophylaxis during (mostly aspirin and low molecular weight heparin) and 1/4 of respondents (25%) commonly prescribe VTE prophylaxis after discharge (mostly aspirin). Of note, respectively 13% and 9% of participants observed at least one DVT and one PE related to right-sided ablation or EP study within the last year in their center. The present survey shows that only a minority of operators routinely gives intraprocedural intravenous heparin and prescribes VTE prophylaxis after right-sided EP procedures. Compared to left-sided procedures like atrial fibrillation (AF) ablation, there are no consistent systematic antithrombotic management strategies.

Prophylactic Inferior Vena Cava Filters for Venous Thromboembolism in Adults With Trauma: An Updated Systematic Review and Meta-Analysis.

Background: Trauma is an independent risk factor for venous thromboembolism (VTE). Due to contraindications or delay in starting pharmacological prophylaxis among trauma patients with a high risk of bleeding, the inferior vena cava (IVC) filter has been utilized as alternative prevention for pulmonary embolism (PE). Albeit, its clinical efficacy has remained uncertain. Therefore, we performed an updated systematic review and meta-analysis on the effectiveness and safety of prophylactic IVC filters in severely injured patients. Methods: Three databases (MEDLINE, EMBASE, and Cochrane) were searched from August 1, 2012, to October 27, 2021. Independent reviewers performed data extraction and quality assessment. Relative risk (RR) at 95% confidence interval (CI) pooled in a randomized meta-analysis. A parallel clinical practice guideline committee assessed the certainty of evidence using the GRADE approach. The outcomes of interest included VTE, PE, deep venous thrombosis, mortality, and IVC filter complications. Results: We included 10 controlled studies (47 140 patients), of which 3 studies (310 patients) were randomized controlled trials (RCTs) and 7 were observational studies (46 830 patients). IVC filters demonstrated no significant reduction in PE and fatal PE (RR, 0.27; 95% CI, 0.06-1.28 and RR, 0.32; 95% CI, 0.01-7.84, respectively) by pooling RCTs with low certainty. However, it demonstrated a significant reduction in the risk of PE and fatal PE (RR, 0.25; 95% CI, 0.12-0.55 and RR, 0.09; 95% CI, 0.011-0.81, respectively) by pooling observational studies with very low certainty. IVC filter did not improve mortality in both RCTs and observational studies (RR, 1.44; 95% CI, 0.86-2.43 and RR, 0.63; 95% CI, 0.3-1.31, respectively). Conclusion: In trauma patients, moderate risk reduction of PE and fatal PE was demonstrated among observational data but not RCTs. The desirable effect is not robust to outweigh the undesirable effects associated with IVC filter complications. Current evidence suggests against routinely using prophylactic IVC filters.

Intravascular Tumor Extension and Pulmonary Tumor Embolism in Children With Solid Malignancies: Is There a Role for Inferior Vena Cava Filters?

Intravascular tumor extension is an uncommon complication of solid malignancies that, when present in the inferior vena cava (IVC), can result in fatal pulmonary tumor embolism. Currently, neoadjuvant chemotherapy and surgery are the mainstays of treatment; however, there are no consensus guidelines for management. We describe three cases of pediatric solid malignancies with associated IVC extension and pulmonary tumor embolism. We hypothesize that there is scope for IVC filter placement in such cases to mitigate the risk of fatal pulmonary tumor embolism.

Prophylactic anticoagulants for non-hospitalised people with COVID-19.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has impacted healthcare systems worldwide. Multiple reports on thromboembolic complications related to COVID-19 have been published, and researchers have described that people with COVID-19 are at high risk for developing venous thromboembolism (VTE). Anticoagulants have been used as pharmacological interventions to prevent arterial and venous thrombosis, and their use in the outpatient setting could potentially reduce the prevalence of vascular thrombosis and associated mortality in people with COVID-19. However, even lower doses used for a prophylactic purpose may result in adverse events such as bleeding. It is important to consider the evidence for anticoagulant use in non-hospitalised people with COVID-19. OBJECTIVES: To evaluate the benefits and harms of prophylactic anticoagulants versus active comparators, placebo or no intervention, or non-pharmacological interventions in non-hospitalised people with COVID-19. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 18 April 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing prophylactic anticoagulants with placebo or no treatment, another active comparator, or non-pharmacological interventions in non-hospitalised people with COVID-19. We included studies that compared anticoagulants with a different dose of the same anticoagulant. We excluded studies with a duration of under two weeks. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. Our primary outcomes were all-cause mortality, VTE (deep vein thrombosis (DVT) or pulmonary embolism (PE)), and major bleeding. Our secondary outcomes were DVT, PE, need for hospitalisation, minor bleeding, adverse events, and quality of life. We used GRADE to assess the certainty of the evidence. MAIN RESULTS: We included five RCTs with up to 90 days of follow-up (short term). Data were available for meta-analysis from 1777 participants. Anticoagulant compared to placebo or no treatment Five studies compared anticoagulants with placebo or no treatment and provided data for three of our outcomes of interest (all-cause mortality, major bleeding, and adverse events). The evidence suggests that prophylactic anticoagulants may lead to little or no difference in all-cause mortality (risk ratio (RR) 0.36, 95% confidence interval (CI) 0.04 to 3.61; 5 studies; 1777 participants; low-certainty evidence) and probably reduce VTE from 3% in the placebo group to 1% in the anticoagulant group (RR 0.36, 95% CI 0.16 to 0.85; 4 studies; 1259 participants; number needed to treat for an additional beneficial outcome (NNTB) = 50; moderate-certainty evidence). There may be little to no difference in major bleeding (RR 0.36, 95% CI 0.01 to 8.78; 5 studies; 1777 participants; low-certainty evidence). Anticoagulants probably result in little or no difference in DVT (RR 1.02, 95% CI 0.30 to 3.46; 3 studies; 1009 participants; moderate-certainty evidence), but probably reduce the risk of PE from 2.7% in the placebo group to 0.7% in the anticoagulant group (RR 0.25, 95% CI 0.08 to 0.79; 3 studies; 1009 participants; NNTB 50; moderate-certainty evidence). Anticoagulants probably lead to little or no difference in reducing hospitalisation (RR 1.01, 95% CI 0.59 to 1.75; 4 studies; 1459 participants; moderate-certainty evidence) and may lead to little or no difference in adverse events (minor bleeding, RR 2.46, 95% CI 0.90 to 6.72; 5 studies, 1777 participants; low-certainty evidence). Anticoagulant compared to a different dose of the same anticoagulant One study compared anticoagulant (higher-dose apixaban) with a different (standard) dose of the same anticoagulant and reported five relevant outcomes. No cases of all-cause mortality, VTE, or major bleeding occurred in either group during the 45-day follow-up (moderate-certainty evidence). Higher-dose apixaban compared to standard-dose apixaban may lead to little or no difference in reducing the need for hospitalisation (RR 1.89, 95% CI 0.17 to 20.58; 1 study; 278 participants; low-certainty evidence) or in the number of adverse events (minor bleeding, RR 0.47, 95% CI 0.09 to 2.54; 1 study; 278 participants; low-certainty evidence). Anticoagulant compared to antiplatelet agent One study compared anticoagulant (apixaban) with antiplatelet agent (aspirin) and reported five relevant outcomes. No cases of all-cause mortality or major bleeding occurred during the 45-day follow-up (moderate-certainty evidence). Apixaban may lead to little or no difference in VTE (RR 0.36, 95% CI 0.01 to 8.65; 1 study; 279 participants; low-certainty evidence), need for hospitalisation (RR 3.20, 95% CI 0.13 to 77.85; 1 study; 279 participants; low-certainty evidence), or adverse events (minor bleeding, RR 2.13, 95% CI 0.40 to 11.46; 1 study; 279 participants; low-certainty evidence). No included studies reported on quality of life or investigated anticoagulants compared to a different anticoagulant, or anticoagulants compared to non-pharmacological interventions. AUTHORS' CONCLUSIONS: We found low- to moderate-certainty evidence from five RCTs that prophylactic anticoagulants result in little or no difference in major bleeding, DVT, need for hospitalisation, or adverse events when compared with placebo or no treatment in non-hospitalised people with COVID-19. Low-certainty evidence indicates that prophylactic anticoagulants may result in little or no difference in all-cause mortality when compared with placebo or no treatment, but moderate-certainty evidence indicates that prophylactic anticoagulants probably reduce the incidence of VTE and PE. Low-certainty evidence suggests that comparing different doses of the same prophylactic anticoagulant may result in little or no difference in need for hospitalisation or adverse events. Prophylactic anticoagulants may result in little or no difference in risk of VTE, hospitalisation, or adverse events when compared with antiplatelet agents (low-certainty evidence). Given that there were only short-term data from one study, these results should be interpreted with caution. Additional trials of sufficient duration are needed to clearly determine any effect on clinical outcomes.

Oral direct thrombin inhibitors or oral factor Xa inhibitors versus conventional anticoagulants for the treatment of pulmonary embolism.

BACKGROUND: Pulmonary embolism (PE) is a potentially life-threatening condition in which a clot can migrate from the deep veins, most commonly in the leg, to the lungs. Conventional treatment of PE used unfractionated heparin (UFH), low molecular weight heparin (LMWH), fondaparinux, and vitamin K antagonists (VKAs). Recently, two forms of direct oral anticoagulants (DOACs) have been developed: oral direct thrombin inhibitors (DTIs) and oral factor Xa inhibitors. DOACs have characteristics that may be favourable to conventional treatment, including oral administration, a predictable effect, no need for frequent monitoring or re-dosing, and few known drug interactions. This review reports the efficacy and safety of these drugs in the long-term treatment of PE (minimum duration of three months). This is an update of a Cochrane Review first published in 2015.  OBJECTIVES: To assess the efficacy and safety of oral DTIs and oral factor Xa inhibitors versus conventional anticoagulants for the long-term treatment of PE. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL databases, the World Health Organization International Clinical Trials Registry Platform and the ClinicalTrials.gov trials registers to 2 March 2022. We checked the reference lists of relevant articles for additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in which people with a PE confirmed by standard imaging techniques were allocated to receive an oral DTI or an oral factor Xa inhibitor compared with a conventional anticoagulant or compared with each other for the long-term treatment of PE (minimum duration three months). DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were recurrent PE, recurrent venous thromboembolism (VTE), and deep vein thrombosis (DVT). Secondary outcomes were all-cause mortality, major bleeding, and health-related quality of life. We used GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: We identified five additional RCTs with 1484 participants for this update. Together with the previously included trials, we have included ten RCTs with a total of 13,073 participants. Two studies investigated an oral DTI (dabigatran) and eight studies investigated oral factor Xa inhibitors (three rivaroxaban, three apixaban, and two edoxaban). The studies were of good methodological quality overall.  Meta-analysis showed no clear difference in the efficacy and safety of oral DTI compared with conventional anticoagulation in preventing recurrent PE (odds ratio (OR) 1.02, 95% confidence interval (CI) 0.50 to 2.04; 2 studies, 1602 participants; moderate-certainty evidence), recurrent VTE (OR 0.93, 95% CI 0.52 to 1.66; 2 studies, 1602 participants; moderate-certainty evidence), DVT (OR 0.79, 95% CI 0.29 to 2.13; 2 studies, 1602 participants; moderate-certainty evidence), and major bleeding (OR 0.50, 95% CI 0.15 to 1.68; 2 studies, 1527 participants; moderate-certainty evidence). We downgraded the certainty of evidence by one level for imprecision due to the low number of events. There was also no clear difference between the oral factor Xa inhibitors and conventional anticoagulation in the prevention of recurrent PE (OR 0.92, 95% CI 0.66 to 1.29; 3 studies, 8186 participants; moderate-certainty evidence), recurrent VTE (OR 0.83, 95% CI 0.66 to 1.03; 8 studies, 11,416 participants; moderate-certainty evidence), DVT (OR 0.77, 95% CI 0.48 to 1.25; 2 studies, 8151 participants; moderate-certainty evidence), all-cause mortality (OR 1.16, 95% CI 0.79 to 1.70; 1 study, 4817 participants; moderate-certainty evidence) and major bleeding (OR 0.71, 95% CI 0.36 to 1.41; 8 studies, 11,447 participants; low-certainty evidence); the heterogeneity for major bleeding was significant (I2 = 79%). We downgraded the certainty of the evidence to moderate and low because of imprecision due to the low number of events and inconsistency due to clinical heterogeneity. None of the included studies measured health-related quality of life. AUTHORS' CONCLUSIONS: Available evidence shows there is probably little or no difference between DOACs and conventional anticoagulation in the prevention of recurrent PE, recurrent VTE, DVT, all-cause mortality, and major bleeding. The certainty of evidence was moderate or low. Future large clinical trials are required to identify if individual drugs differ in effectiveness and bleeding risk, and to explore effect differences in subgroups, including people with cancer and obesity.

Oral direct thrombin inhibitors or oral factor Xa inhibitors versus conventional anticoagulants for the treatment of deep vein thrombosis.

BACKGROUND: Deep vein thrombosis (DVT) is a condition in which a clot forms in the deep veins, most commonly of the leg. It occurs in approximately one in 1000 people. If left untreated, the clot can travel up to the lungs and cause a potentially life-threatening pulmonary embolism (PE). Previously, a DVT was treated with the anticoagulants heparin and vitamin K antagonists. However, two forms of direct oral anticoagulants (DOACs) have been developed: oral direct thrombin inhibitors (DTIs) and oral factor Xa inhibitors, which have characteristics that may be favourable compared to conventional treatment, including oral administration, a predictable effect, lack of frequent monitoring or dose adjustment and few known drug interactions. DOACs are now commonly being used for treating DVT: recent guidelines recommended DOACs over conventional anticoagulants for both DVT and PE treatment. This Cochrane Review was first published in 2015. It was the first systematic review to measure the effectiveness and safety of these drugs in the treatment of DVT. This is an update of the 2015 review.  OBJECTIVES: To assess the effectiveness and safety of oral DTIs and oral factor Xa inhibitors versus conventional anticoagulants for the long-term treatment of DVT. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL databases and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 1 March 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in which people with a DVT, confirmed by standard imaging techniques, were allocated to receive an oral DTI or an oral factor Xa inhibitor compared with conventional anticoagulation or compared with each other for the treatment of DVT.  DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were recurrent venous thromboembolism (VTE), recurrent DVT and PE. Secondary outcomes included all-cause mortality, major bleeding, post-thrombotic syndrome (PTS) and quality of life (QoL). We used GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: We identified 10 new studies with 2950 participants for this update. In total, we included 21 RCTs involving 30,895 participants. Three studies investigated oral DTIs (two dabigatran and one ximelagatran), 17 investigated oral factor Xa inhibitors (eight rivaroxaban, five apixaban and four edoxaban) and one three-arm trial investigated both a DTI (dabigatran) and factor Xa inhibitor (rivaroxaban). Overall, the studies were of good methodological quality. Meta-analysis comparing DTIs to conventional anticoagulation showed no clear difference in the rate of recurrent VTE (odds ratio (OR) 1.17, 95% confidence interval (CI) 0.83 to 1.65; 3 studies, 5994 participants; moderate-certainty evidence), recurrent DVT (OR 1.11, 95% CI 0.74 to 1.66; 3 studies, 5994 participants; moderate-certainty evidence), fatal PE (OR 1.32, 95% CI 0.29 to 6.02; 3 studies, 5994 participants; moderate-certainty evidence), non-fatal PE (OR 1.29, 95% CI 0.64 to 2.59; 3 studies, 5994 participants; moderate-certainty evidence) or all-cause mortality (OR 0.66, 95% CI 0.41 to 1.08; 1 study, 2489 participants; moderate-certainty evidence). DTIs reduced the rate of major bleeding (OR 0.58, 95% CI 0.38 to 0.89; 3 studies, 5994 participants; high-certainty evidence).   For oral factor Xa inhibitors compared with conventional anticoagulation, meta-analysis demonstrated no clear difference in recurrent VTE (OR 0.85, 95% CI 0.71 to 1.01; 13 studies, 17,505 participants; moderate-certainty evidence), recurrent DVT (OR 0.70, 95% CI 0.49 to 1.01; 9 studies, 16,439 participants; moderate-certainty evidence), fatal PE (OR 1.18, 95% CI 0.69 to 2.02; 6 studies, 15,082 participants; moderate-certainty evidence), non-fatal PE (OR 0.93, 95% CI 0.68 to 1.27; 7 studies, 15,166 participants; moderate-certainty evidence) or all-cause mortality (OR 0.87, 95% CI 0.67 to 1.14; 9 studies, 10,770 participants; moderate-certainty evidence). Meta-analysis showed a reduced rate of major bleeding with oral factor Xa inhibitors compared with conventional anticoagulation (OR 0.63, 95% CI 0.45 to 0.89; 17 studies, 18,066 participants; high-certainty evidence).  AUTHORS' CONCLUSIONS: The current review suggests that DOACs may be superior to conventional therapy in terms of safety (major bleeding), and are probably equivalent in terms of efficacy. There is probably little or no difference between DOACs and conventional anticoagulation in the prevention of recurrent VTE, recurrent DVT, pulmonary embolism and all-cause mortality. DOACs reduced the rate of major bleeding compared to conventional anticoagulation. The certainty of evidence was moderate or high.

Sex differences in thromboprophylaxis of the critically ill: a secondary analysis of a randomized trial.

PURPOSE: Venous thromboembolism (VTE) is a common complication of critical illness. Sex- or gender-based analyses are rarely conducted and their effect on outcomes is unknown. We assessed for an effect modification of thromboprophylaxis (dalteparin or unfractionated heparin [UFH]) by sex on thrombotic (deep venous thrombosis [DVT], pulmonary embolism [PE], VTE) and mortality outcomes in a secondary analysis of the Prophylaxis for Thromboembolism in Critical Care Trial (PROTECT). METHODS: We conducted unadjusted analyses using Cox proportional hazards analysis, stratified by centre and admission diagnostic category, including sex, treatment, and an interaction term. Additionally, we performed adjusted analyses and assessed the credibility of our findings. RESULTS: Critically ill female (n = 1,614) and male (n = 2,113) participants experienced similar rates of DVT, proximal DVT, PE, any VTE, ICU death, and hospital death. In unadjusted analyses, we did not find significant differences in treatment effect favouring males (vs females) treated with dalteparin (vs UFH) for proximal leg DVT, any DVT, or any PE, but found a statistically significant effect (moderate certainty) favouring dalteparin in males for any VTE (males: hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.52 to 0.96 vs females: HR, 1.16; 95% CI, 0.81 to 1.68; P = 0.04). This effect remained after adjustment for baseline characteristics (males: HR, 0.70; 95% CI, 0.52 to 0.96 vs females: HR, 1.17; 95% CI, 0.81 to 1.68; P = 0.04) and weight (males: HR, 0.70; 95% CI, 0.52 to 0.96 vs females: HR, 1.20; 95% CI, 0.83 to 1.73; P = 0.03). We did not identify a significant effect modification by sex on mortality. CONCLUSIONS: We found an effect modification by sex of thromboprophylaxis on VTE in critically ill patients that requires confirmation. Our findings highlight the need for sex- and gender-based analyses in acute care research.

RéSUMé: OBJECTIF: La maladie thromboembolique veineuse (MTEV) est une complication fréquente au cours des maladies critiques. Des analyses basées sur le sexe ou le genre sont rarement effectuées et leur effet sur les critères d'évaluation est inconnu. Nous avons évalué une modification de l'effet de la thromboprophylaxie (daltéparine ou héparine non fractionnée [HNF]) selon le sexe sur la maladie thrombotique (thrombose veineuse profonde [TVP], embolie pulmonaire [EP], MTEV) et sur les critères de mortalité au cours d'une analyse secondaire de l'étude PROTECT (essai de prophylaxie de la thromboembolie en soins critiques). MéTHODE: Nous avons réalisé des analyses non ajustées au moyen d'une analyse des risques proportionnels de Cox, stratifiées par site et catégorie diagnostique à l'admission, incluant le sexe, le traitement et un terme d'interaction. Nous avons aussi réalisé des analyses ajustées et avons évalué la crédibilité de nos constatations. RéSULTATS: Les participant·es dans un état critique de sexe féminin (n = 1 614) et masculin (n = 2 113) ont présenté des taux semblables de TVP, EP, et MTEV de tout type, de décès en soins intensifs et de décès en milieu hospitalier. Nous n'avons pas trouvé de différences significatives dans les analyses non ajustées en faveur des hommes (par rapport aux femmes) traités par la daltéparine (par rapport à l'HNF) pour la TVP de la cuisse, la TVP de tout type, ou tout type d'EP; en revanche, nous avons trouvé un effet statistiquement significatif (certitude modérée) en faveur de la daltéparine pour la MTEV de tout type (hommes : rapport de risque [RR], 0,71; intervalle de confiance [IC] à 95 %, 0,52 à 0,96 par rapport aux femmes : RR, 1,16; IC 95 %, 0,81 à 1,68; P = 0,04). Cet effet a persisté après ajustement pour les caractéristiques à l'inclusion (hommes : RR, 0,70; IC 95 %, 0,52 à 0,96 par rapport aux femmes : RR, 1,17; IC 95 %, 0,81 à 1,68; P = 0,04) et le poids (hommes : RR, 0,70; IC 95 %, 0,52 à 0,96 par rapport aux femmes : RR, 1,20; IC 95 %, 0,83 à 1,73; P = 0,03). Nous n'avons pas identifié de modification significative de l'effet en fonction du sexe sur la mortalité. CONCLUSION: Nous avons trouvé une modification de l'effet en fonction du sexe sur la thromboprophylaxie sur la MTEV chez les patient·es en état critique; cette constatation nécessite une confirmation. Nos constatations soulignent le besoin d'analyses en fonction du sexe et du genre dans la recherche sur les soins aigus.