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Journal of Thrombosis and Haemostasis :... Dec 2022In recent years, many important advances have been seen in anticoagulation therapy. However, bleeding risk is still a major concern. Factor XI (FXI) inhibition has... (Meta-Analysis)
Meta-Analysis
Achieving higher efficacy without compromising safety with factor XI inhibitors versus low molecular weight heparin for the prevention of venous thromboembolism in major orthopedic surgery-Systematic review and meta-analysis.
BACKGROUND
In recent years, many important advances have been seen in anticoagulation therapy. However, bleeding risk is still a major concern. Factor XI (FXI) inhibition has emerged as a potential advantageous target to minimize this risk.
OBJECTIVES
We conducted a systematic review and meta-analysis of current evidence on FXI inhibitors for thromboprophylaxis in major orthopedic surgery.
METHODS
We performed a systematic search of electronic databases (PubMed, CENTRAL, and Scopus) until May of 2022. Studies were considered eligible if they were randomized controlled trials (RCTs) evaluating FXI inhibitors in thromboprophylaxis versus low molecular weight heparin (LMWH). For analysis purposes, we considered efficacy (venous thromboembolism [VTE], symptomatic VTE) and safety (major and clinically relevant non-major [CRNM] bleeding events, major bleeding events, blood transfusion necessities, adverse events, major adverse events) outcomes.
RESULTS
Overall, four RCTs were included, with a total of 2269 patients, 372 VTE events, and 50 major or CRNM bleeding events. Regarding efficacy outcomes, FXI inhibitors were associated with a significant reduction in the incidence of VTE events (odds ratio [OR] 0.50; 95% confidence interval [CI: 0.36, 0.69]). Concerning safety outcomes, FXI inhibitors significantly reduced major or CRNM bleeding events (OR 0.41; 95% CI [0.22, 0.75]). It was also associated with a lower percentage of patients needing a blood transfusion, despite not meeting statistical significance (OR 0.69; 95% CI [0.32, 1.48]). Incidence of adverse events and major adverse events were similar between groups.
CONCLUSION
Factor XI inhibitors showed a significant reduction in the incidence of VTE and bleeding events among patients submitted to major orthopedic surgery.
Topics: Humans; Heparin, Low-Molecular-Weight; Venous Thromboembolism; Factor XI; Anticoagulants; Hemorrhage; Orthopedic Procedures; Heparin
PubMed: 36128769
DOI: 10.1111/jth.15890 -
Environmental Pollution (Barking, Essex... Sep 2023Phthalates are chemicals widely used in plastic-based consumer products, and human exposure is universal. They are classified as endocrine disruptors, and specific... (Meta-Analysis)
Meta-Analysis Review
Phthalates are chemicals widely used in plastic-based consumer products, and human exposure is universal. They are classified as endocrine disruptors, and specific phthalate metabolites have been associated with an increased risk of cardiometabolic diseases. The aim of this study was to assess the association between phthalate exposure and the metabolic syndrome in the general population. A comprehensive literature search was performed in four databases (Web of Science, Medline, PubMed, and Scopus). We included all the observational studies that evaluate the association between phthalate metabolites and the metabolic syndrome available until January 31st, 2023. Pooled Odds Ratios (OR) and their 95% confidence intervals were calculated by using the inverse-variance weighted method. Nine cross-sectional studies and 25,365 participants aged from 12 to 80 were included. Comparing extreme categories of phthalate exposure, the pooled ORs for the metabolic syndrome were: 1.08 (95% CI, 1.02-1.16, I = 28%) for low molecular weight phthalates, and 1.11 (95% CI, 1.07-1.16, I = 7%) for high molecular weight phthalates. For individual phthalate metabolites, the pooled ORs that achieved statistical significance were: 1.13 (95% CI, 1.00-1.27, I = 24%) for MiBP; 1.89 (95% CI, 1.17-3.07, I = 15%) for MMP in men; 1.12 (95% CI, 1.00-1.25, I = 22%) for MCOP; 1.09 (95% CI, 0.99-1.20, I = 0%) for MCPP; 1.16 (95% CI, 1.05-1.28, I = 6%) for MBzP; and 1.16 (95% CI, 1.09-1.24, I = 14%) for DEHP (including ΣDEHP and its metabolites). In conclusion, both low molecular weight and high molecular weight phthalates were associated with an 8 and 11% higher prevalence of the MetS, respectively. The exposure to six specific phthalate metabolites was associated with a higher prevalence of the MetS.
Topics: Male; Humans; Metabolic Syndrome; Environmental Pollutants; Cross-Sectional Studies; Phthalic Acids; Plastics; Environmental Exposure
PubMed: 37328121
DOI: 10.1016/j.envpol.2023.121957 -
Journal of Clinical Pharmacy and... Aug 2020Low-molecular-weight heparin (LMWH) is widely used in the prevention and treatment of venous thromboembolism (VTE), and anti-Xa assay is the gold standard for... (Meta-Analysis)
Meta-Analysis
WHAT IS KNOWN AND OBJECTIVE
Low-molecular-weight heparin (LMWH) is widely used in the prevention and treatment of venous thromboembolism (VTE), and anti-Xa assay is the gold standard for monitoring LMWH. However, it is still controversial whether monitoring is necessary for patients receiving LMWH therapy. Therefore, we conducted a meta-analysis to explore the effect of anti-Xa monitoring on the safety and efficacy of LMWH anticoagulant therapy.
METHODS
PubMed, EMBASE, Web of Science and The Cochrane Library were searched on 27 May 2019 for eligible studies published in English. Odds ratio (OR) and 95% confidence intervals (CI) were estimated (Mantel-Haenszel method) using Review Manager version 5.3 software. The systematic review and meta-analysis was performed according to the recommendations of the Preferred Reporting Items of Systematic Reviews and Meta-Analyses (PRISMA) statement.
RESULTS AND DISCUSSION
Six studies involving 1617 patients were eligible for our meta-analysis, with 724 patients in the anti-Xa monitoring group and 893 patients in the control group. There was no significant difference in the incidence of bleeding events between the two groups, while the anti-Xa monitoring group had a lower incidence of venous thromboembolism events (OR 0.44, 95% CI 0.29-0.68, P = .0002). Subgroup analysis showed that the incidence of venous thromboembolism events in the anti-Xa monitoring group was lower than that in the control group when the trough level was monitored (OR 0.40, 95% CI 0.25-0.63, P < .0001), while there was no significant difference between the two groups when the peak level was monitored.
WHAT IS NEW AND CONCLUSION
Patients receiving LMWH anticoagulant therapy to prevent VTE can benefit from anti-Xa monitoring, for which the trough level may be the more appropriate time status to monitor.
Topics: Anticoagulants; Blood Coagulation; Factor Xa; Factor Xa Inhibitors; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Odds Ratio; Venous Thromboembolism
PubMed: 32449992
DOI: 10.1111/jcpt.13169 -
Journal of Thrombosis and Haemostasis :... Jul 2014Tumors may exploit the coagulation system to enhance the survival and dissemination of cancer cells. Some studies have suggested that heparin and low molecular weight... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Tumors may exploit the coagulation system to enhance the survival and dissemination of cancer cells. Some studies have suggested that heparin and low molecular weight heparin (LMWH) have antitumor effects. We reported a previous meta-analysis that suggested a modest improvement in overall survival with the use of LMWH in patients with cancer. Herein, we present the results of an updated systematic review and meta-analysis.
OBJECTIVE
To evaluate the effect of LMWH as compared with placebo or no anticoagulant on the overall survival in patients with solid cancers.
METHODS
We conducted a systematic review and meta-analysis of randomized trials evaluating the use of LMWH vs. placebo or no anticoagulant in cancer patients without venous thrombosis. A meta-analysis was conducted with a random-effects model, and data were analyzed by the use of odds ratios (ORs) and relative risks (RRs) calculated for 1-year overall mortality.
RESULTS
We identified 724 potentially relevant studies, nine of which met our inclusion criteria, and reported data on 1-year overall mortality. Studies were heterogeneous regarding types of cancer and interventions, and included 5987 patients, 98.4% of whom had advanced-stage disease (III and IV). There was no discernible effect on mortality with the use of LMWH (pooled OR 0.87, 95% CI 0.70-1.08; RR 0.94, 95% CI 0.86-1.04).
CONCLUSIONS
In contrast to the previous study, these results did not show a survival benefit in cancer patients receiving LMWH. The effect of LMWH on overall survival in patients with limited-stage disease still is unknown.
Topics: Aged; Anticoagulants; Blood Coagulation; Female; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Neoplasms; Odds Ratio; Randomized Controlled Trials as Topic; Risk; Treatment Outcome; Venous Thrombosis
PubMed: 24796727
DOI: 10.1111/jth.12595 -
World Journal of Surgical Oncology Feb 2024Direct oral anticoagulants (DOACs) used as an alternative to low-molecular-weight heparin (LMWH) for thromboprophylaxis after cancer surgery for venous thromboembolic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Direct oral anticoagulants (DOACs) used as an alternative to low-molecular-weight heparin (LMWH) for thromboprophylaxis after cancer surgery for venous thromboembolic events (VTE) remains unclear. This study aimed to investigate the efficacy and safety of DOACs versus LMWH in these patients.
MATERIALS AND METHODS
A search of EMBASE, MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science was carried out and included all randomized controlled trials (RCTs) and observational studies that directly compared DOACs with LMWH for thromboprophylaxis in patients after cancer surgery through July 25, 2023. The primary efficacy and safety outcomes were VTE, major bleeding, and clinically relevant non-major bleeding (CRNMB) within 30 days of surgery. The risk of bias was assessed using the Cochrane Risk of Bias 2 (RoB2) tool for RCTs and ROBINS-I tool for non-randomized studies. This study was registered in PROSPERO (CRD42023445386).
RESULTS
We retrieved 5149articles, selected 27 for eligibility, and included 10 studies (three RCTs and seven observational studies) encompassing 3054 patients who underwent postoperative thromboprophylaxis with DOACs (41%) or LMWH (59%). Compared to LMWH thromboprophylaxis, DOACs had a comparable risk of VTE (RR:0.69[95% CI:0.46-1.02], I = 0%), major bleeding (RR:1.55 [95% CI:0.82-2.93], I = 2%), and CRNMB (RR, 0.89 [95% CI, 0.4-1.98], I = 31%) during the 30-day postoperative period. Subgroup analysis of VTE and major bleeding suggested no differences according to study type, extended thromboprophylaxis, tumor types, or different types of DOAC.
CONCLUSION
DOACs are potentially effective alternatives to LMWH for thromboprophylaxis in patients undergoing cancer surgery, without increasing the risk of major bleeding events.
Topics: Humans; Heparin, Low-Molecular-Weight; Anticoagulants; Venous Thromboembolism; Hemorrhage; Neoplasms
PubMed: 38403630
DOI: 10.1186/s12957-024-03341-5 -
The Lancet. Oncology Oct 2019Venous thromboembolism (VTE) is the second leading cause of death in patients with cancer. These patients are at a high risk of VTE recurrence and bleeding during...
Venous thromboembolism (VTE) is the second leading cause of death in patients with cancer. These patients are at a high risk of VTE recurrence and bleeding during anticoagulant therapy. The International Initiative on Thrombosis and Cancer is an independent academic working group aimed at establishing a global consensus for the treatment and prophylaxis of VTE in patients with cancer. The International Initiative on Thrombosis and Cancer last updated its evidence-based clinical practice guidelines in 2016 with a free, web-based mobile phone application, which was subsequently endorsed by the International Society on Thrombosis and Haemostasis. The 2019 International Initiative on Thrombosis and Cancer clinical practice guidelines, which are based on a systematic review of the literature published up to December, 2018, are presented along with a Grading of Recommendations Assessment Development and Evaluation scale methods, with the support of the French National Cancer Institute. These guidelines were reviewed by an expanded international advisory committee and endorsed by the International Society on Thrombosis and Haemostasis. Results from head-to-head clinical trials that compared direct oral anticoagulant with low-molecular-weight heparin are also summarised, along with new evidence for the treatment and prophylaxis of VTE in patients with cancer.
Topics: Anticoagulants; Central Venous Catheters; Factor Xa Inhibitors; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Vena Cava Filters; Venous Thromboembolism; Vitamin K
PubMed: 31492632
DOI: 10.1016/S1470-2045(19)30336-5 -
International Journal of Surgery... Jun 2018To systematically evaluate the prophylaxis efficacy of low-molecular-weight heparin (LMWH) in the prevention of deep venous thrombosis (DVT) after total knee... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
To systematically evaluate the prophylaxis efficacy of low-molecular-weight heparin (LMWH) in the prevention of deep venous thrombosis (DVT) after total knee arthroplasty (TKA).
METHOD
PubMed, Cochrane, Embase, Wanfang, CNKI, and VIP databases were searched by index words to identify the eligible RCTs; relevant literature sources were also searched. The latest research was conducted in March 2017. Relative risks (RR), mean difference (MD), and their corresponding 95% confidence intervals (95% CIs) were used to analyze the main outcomes.
RESULT
A total of 22 articles were included in the meta-analysis with a total number of 11,320 patients (5543 in the LMWH group and 5777 in the control group). The results indicated that in the LMWH group, the incidence of DVT (OR: 0.57, 95% CI: 0.41-0.77) and wound complications (SMD: 0.96, 95% CI: 0.75-1.22) was significantly lower than that in the control group. Furthermore, LMWH also increased the occurrence of bleeding event (OR: 1.57, 95% CI: 1.31-1.88) and the total blood transfused (SMD: 0.12, 95% CI: 0.04-0.19). However, no statistical difference was found in blood loss (SMD: -0.26, 95% CI: -0.65-0.14) between the two group. In the subgroup analysis, the incidence of DVT was significantly decreased in the ardeparin sodium group (OR: 0.70, 95%CI: 0.53-0.94) and the dalteparin group (OR:0.40, 95%CI:0.32-0.50).
CONCLUSION
Our meta-analysis demonstrated that LMWH is obviously efficacious in the prophylaxis of DVT after TKA. However, it has some negative effects, such as the increase in the number of bleeding events and the total blood transfused.
Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Knee; Blood Transfusion; Dalteparin; Female; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Postoperative Complications; Postoperative Hemorrhage; Venous Thrombosis
PubMed: 29733996
DOI: 10.1016/j.ijsu.2018.04.059 -
Annals of Surgery Jan 2022Trauma patients are at high risk of VTE. We summarize the efficacy and safety of LMWH versus UFH for the prevention of VTE in trauma patients. (Meta-Analysis)
Meta-Analysis
Efficacy and Safety of Low Molecular Weight Heparin Versus Unfractionated Heparin for Prevention of Venous Thromboembolism in Trauma Patients: A Systematic Review and Meta-analysis.
PURPOSE
Trauma patients are at high risk of VTE. We summarize the efficacy and safety of LMWH versus UFH for the prevention of VTE in trauma patients.
METHODS
We searched 6 databases from inception through March 12, 2021. We included randomized controlled trials (RCTs) or observational studies comparing LMWH versus UFH for thromboprophylaxis in adult trauma patients. We pooled effect estimates across RCTs and observational studies separately, using random-effects model and inverse variance weighting. We assessed risk of bias using the Cochrane tool for RCTs and the Risk of Bias in Non-Randomized Studies (ROBINS)-I tool for observational studies and assessed certainty of findings using Grading of Recommendations, Assessment, Development and Evaluations methodology.
RESULTS
We included 4 RCTs (879 patients) and 8 observational studies (306,747 patients). Based on pooled RCT data, compared to UFH, LMWH reduces deep vein thrombosis (RR 0.67, 95% CI 0.50 to 0.88, moderate certainty) and VTE (RR 0.68, 95% CI 0.51 to 0.90, moderate certainty). As compared to UFH, LMWH may reduce pulmonary embolism [adjusted odds ratio from pooled observational studies 0.56 (95% CI 0.50 to 0.62)] and mortality (adjusted odds ratio from pooled observational studies 0.54, 95% CI 0.45 to 0.65), though based on low certainty evidence. There was an uncertain effect on adverse events (RR from pooled RCTs 0.80, 95% CI 0.48 to 1.33, very low certainty) and heparin induced thrombocytopenia [RR from pooled RCTs 0.26 (95% CI 0.03 to 2.38, very low certainty)].
CONCLUSIONS
Among adult trauma patients, LMWH is superior to UFH for deep vein thrombosis and VTE prevention and may additionally reduce pulmonary embolism and mortality. The impact on adverse events and heparin induced thrombocytopenia is uncertain.
Topics: Anticoagulants; Heparin; Heparin, Low-Molecular-Weight; Humans; Pulmonary Embolism; Venous Thromboembolism; Venous Thrombosis; Wounds and Injuries
PubMed: 34387202
DOI: 10.1097/SLA.0000000000005157 -
Clinical and Applied... 2021Cancer-associated thrombosis (CAT) carries significant morbidity and mortality. Low-molecular-weight heparin (LMWH) remains the standard of care, with recent systematic... (Meta-Analysis)
Meta-Analysis
Cancer-associated thrombosis (CAT) carries significant morbidity and mortality. Low-molecular-weight heparin (LMWH) remains the standard of care, with recent systematic studies suggesting the efficacy and safety of rivaroxaban in the treatment of CAT. Uncertainty, however, remains regarding rivaroxaban efficacy and safety in real-world settings. We performed a systematic review and meta-analysis of studies comparing rivaroxaban to LMWH. We searched PubMed, MEDLINE, and EMBASE. The primary outcome was the net clinical benefit (NCB), while rates of major bleeding (MB), venous thromboembolism (VTE), clinically relevant nonmajor bleeding (CRNMB), and all-cause mortality events were secondary outcomes. Seventeen studies were included in the final analysis. Rivaroxaban had a better NCB (relative risk [RR] = 0.82; 95% CI = 0.75-0.89, Q = 10.51, 0%), less VTE events (RR = 0.73, 95% CI = 0.65-0.82, Q = 6.76, = 0%), and lower all-cause mortality (RR = 0.72, 95% CI = 0.57-0.91, Q = 32.8, = 79%) compared to LMWH. Additionally, comparable MB events (RR = 1.07, 95% CI = 0.85-1.33, Q = 16.9, = 11%). However, CRNMB events were higher in the rivaroxaban group (RR = 2.02, 95% CI = 1.46-2.80, Q = 9.9, = 19%). Additional analyses demonstrated consistency of results. Our review encompassing data from randomized and real-world data suggested rivaroxaban superiority compared to LMWH in terms of a better NCB, fewer VTE events, lower all-cause mortality, and comparable MB risk while carrying a higher risk of CRNMB. These findings support the use of rivaroxaban in the treatment of CAT. Additionally, it warrants a sizable randomized controlled study testing the superiority of rivaroxaban versus LMWH formulation and ascertaining bleeding outcomes according to cancer type and site.
Topics: Aged; Factor Xa Inhibitors; Heparin, Low-Molecular-Weight; Humans; Middle Aged; Neoplasms; Rivaroxaban; Thrombosis
PubMed: 33651658
DOI: 10.1177/1076029620940046 -
Pharmacotherapy Sep 2012To evaluate the comparative efficacy and safety of low-molecular-weight heparins (LMWHs) versus other anticoagulants as venous thromboembolism prophylaxis in major... (Comparative Study)
Comparative Study Meta-Analysis Review
STUDY OBJECTIVE
To evaluate the comparative efficacy and safety of low-molecular-weight heparins (LMWHs) versus other anticoagulants as venous thromboembolism prophylaxis in major orthopedic surgery.
DESIGN
Systematic review with meta-analysis of 37 randomized controlled trials.
PATIENTS
Patients undergoing total hip replacement, total knee replacement, or hip fracture surgery who received prophylaxis with a LMWH or another anticoagulant.
MEASUREMENTS AND MAIN RESULTS
We conducted a systematic literature search of the MEDLINE, Cochrane Central Register of Controlled Trials, and Scopus databases (1980-July 2011) to identify randomized controlled trials. Trials were included if they directly compared LMWH prophylaxis with another anticoagulant class and reported outcomes of interest. Compared with patients who received unfractionated heparin (UFH), patients who received LMWHs had fewer pulmonary embolism, total deep vein thrombosis (DVT), major bleeding, and heparin-induced thrombocytopenia events. Compared with patients who received vitamin K antagonists (VKAs), patients who received LMWHs had fewer total DVT and distal DVT events but reported increased major bleeding, minor bleeding, and surgical site bleeding events. Major efficacy end points such as symptomatic venous thromboembolism, pulmonary embolism, and nonfatal pulmonary embolism showed similar benefits of therapy with LMWHs and VKAs. Compared with patients receiving factor Xa inhibitors, patients who received LMWHs had more major venous thromboembolism, pulmonary embolism, total DVT, asymptomatic DVT, proximal DVT, and distal DVT events but fewer major bleeding events. Compared with patients receiving direct thrombin inhibitors (DTIs), patients who received LMWHs had more major venous thromboembolism, total DVT, and proximal DVT events without significantly negatively affecting bleeding. However, patients who received LMWHs had fewer distal DVT events versus those who received DTIs. Subgroup analyses indicated differences based on the surgical procedure and individual drug within certain pharmacologic classes.
CONCLUSION
According to moderate-to-high strength of evidence, LMWH prophylaxis provides additional benefits with less harm compared with UFH. With predominantly moderate strength of evidence, the balance of benefits to harms for factor Xa inhibitors or DTIs compared with LMWHs seems favorable. With predominantly low-to-moderate strength of evidence, the known benefits in total DVT and distal DVT with LMWHs versus VKAs may not be sufficient to counteract the increased risk of bleeding.
Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Hip Fractures; Humans; Randomized Controlled Trials as Topic; Thromboembolism; Vitamin K
PubMed: 22744711
DOI: 10.1002/j.1875-9114.2012.01106.x