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Frontiers in Cardiovascular Medicine 2020Venous thromboembolism (VTE) is highly prevalent in cancer patients. Recent guidelines recommend considering direct oral anticoagulants (DOACs) for the treatment of...
Venous thromboembolism (VTE) is highly prevalent in cancer patients. Recent guidelines recommend considering direct oral anticoagulants (DOACs) for the treatment of cancer-associated thrombosis (CAT). However, direct head-to-head comparisons among DOACs are lacking, and almost no net clinical benefit (NCB) analysis has been performed in patients with CAT. We systematically searched PubMed, EMBASE, Cochrane Library, and ClinicalTrials.gov for randomized controlled trials (RCTs) reporting on recurrent VTE, major bleeding, or clinically relevant bleeding events in patients with CAT who received DOACs and low-molecular-weight heparins. Relative risks (RRs) and 95% confidence intervals (95% CIs) were calculated using a random-effect model. Surface under the cumulative ranking curve (SUCRA) values were calculated, and a trade-off analysis was performed to estimate the NCB. Overall, four RCTs involving 2,894 patients were enrolled. DOACs were more effective than dalteparin in reducing the risk of recurrent VTE (RR: 0.62, 95% CI: 0.44-0.87), with a comparative risk of major bleeding (RR: 1.33, 95% CI: 0.84-2.11) and an increased risk of clinically relevant bleeding (RR: 1.45, 95% CI: 1.05-1.99). No significant difference was observed among individual anticoagulants in terms of recurrent VTE and major bleeding. With respect to the ranking of each anticoagulant for the primary outcome, edoxaban (SUCRA: 69.2) was more effective than dalteparin (SUCRA: 60.7), rivaroxaban (SUCRA: 60.7), and apixaban (SUCRA: 25.5) in reducing VTE recurrence. For major bleeding, apixaban (SUCRA: 76.3) had the highest cumulative ranking probability, followed by edoxaban (SUCRA: 66.4), dalteparin (SUCRA: 28.8), and rivaroxaban (SUCRA: 28.5). Similar results were observed for clinically relevant bleeding. In terms of both benefit and safety outcomes, DOACs, especially edoxaban, seemed to confer a better NCB profile than dalteparin. DOACs are a safe and effective alternative therapy to dalteparin in patients with CAT. Among them, edoxaban might provide a good risk-to-benefit balance. However, because of the lack of head-to-head studies, further investigations are needed to confirm our findings.
PubMed: 33304929
DOI: 10.3389/fcvm.2020.586020 -
The American Journal of Medicine Aug 2011Post-thrombotic syndrome causes considerable morbidity. The Home-LITE study showed a lower incidence of post-thrombotic syndrome and venous ulcers after 3 months of... (Comparative Study)
Comparative Study Review
OBJECTIVE
Post-thrombotic syndrome causes considerable morbidity. The Home-LITE study showed a lower incidence of post-thrombotic syndrome and venous ulcers after 3 months of treating deep vein thrombosis with the low-molecular-weight heparin tinzaparin versus oral anticoagulation. This systematic review examined whether long-term treatment of deep vein thrombosis using low-molecular-weight heparin, rather than oral anticoagulation, reduces development of post-thrombotic syndrome.
METHODS
We identified 9 articles comparing treatment of deep vein thrombosis using long-term low-molecular-weight heparin with any comparator, which reported outcomes relevant to the post-thrombotic syndrome assessed ≥ 3 months post-deep vein thrombosis.
RESULTS
Pooled analysis of 2 studies yielded an 87% risk reduction with low-molecular-weight heparin in the incidence of venous ulcers at ≥ 3 months (P = .019). One study showed an overall odds ratio of 0.77 (P = .001) favoring low-molecular-weight heparin for the presence of 8 patient-reported post-thrombotic syndrome signs and symptoms. Pooled analysis of 5 studies showed a risk ratio for low-molecular-weight heparin versus oral anticoagulation of 0.66 (P < .0001) for complete recanalization of thrombosed veins.
CONCLUSION
These results support the lower incidence of post-thrombotic syndrome and venous ulcers observed in Home-LITE. Long-term treatment with low-molecular-weight heparin rather than oral anticoagulation after a deep vein thrombosis may reduce or prevent development of signs and symptoms associated with post-thrombotic syndrome. Post-thrombotic syndrome and associated acute ulcers may develop more rapidly after deep vein thrombosis than previously recognized.
Topics: Anticoagulants; Dalteparin; Drug Administration Schedule; Enoxaparin; Heparin, Low-Molecular-Weight; Humans; Incidence; Nadroparin; Postthrombotic Syndrome; Severity of Illness Index; Tinzaparin; Varicose Ulcer; Veins; Venous Thrombosis
PubMed: 21787905
DOI: 10.1016/j.amjmed.2011.02.033 -
Pharmacological Research Apr 2021Anticoagulants are essential in the prevention of venous thromboembolism. However, the effectiveness and safety of different anticoagulants have always been... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Anticoagulants are essential in the prevention of venous thromboembolism. However, the effectiveness and safety of different anticoagulants have always been controversial. Therefore, we aimed to expand the sample of anticoagulant results and rank the efficacy and safety of 19 anticoagulants in the prevention of venous thromboembolism when total knee or total hip arthroplasty procedure is performed.
METHODS
A systematic review and network meta-analysis of randomized trials of adult patients undergoing total hip or knee arthroplasty were conducted. The trials were identified from PubMed, Web of Science, Cochrane Library, and Embase databases, in which anticoagulants were used as interventions randomized controlled trial. The incidence of venous embolism and bleeding are the key outcomes of assessing the efficacy of intervention drugs. We used the Physical Therapy Evidence Database (PEDro) to assess risk bias and used pairwise comparison and network meta-analysis with random effects to estimate the summary relative risk. The study has been registered with PROSPERO, number CRD42020200747.
RESULTS
From the 4083 identified manuscripts, 45,067 participants from 53 randomized trials were included in the analysis and randomly assigned to 19 anticoagulants. With Enoxaparin as a control, Rivaroxaban (risk difference 0.07, 95 % credible interval 0.06 to 0.08), Edoxaban (RD 0.09, 95 % CrI 0.08 to 0.11), and Apixaban (RD 0.05, 95 % CrI 0.04 to 0.06) had the best effect in preventing VTE. However, in terms of comprehensive bleeding rate, Apixaban, Edoxaban, and Darexaban were the most effective and stable. Although effective in preventing VTE, bleeding remains relatively high in Rivaroxaban. Enoxaparin is low-molecular-weight heparin that is widely used in clinics, and although its overall efficacy is not the best, its efficacy and safety are very stable.
CONCLUSION
According to the available data, Apixaban, Edoxaban, and Darexaban are better than any anticoagulants in the prevention of VTE and bleeding during total knee or total hip arthroplasty. In our study, Fondaparinux, Eribaxaban, Dalteparin, Betrixaban, Bemiparin, Reviparin, Acenocoumarol, and Tinzaparin were scarce in the included studies, therefore, more evidence is needed to prove their efficacy and safety.
Topics: Anticoagulants; Arthroplasty, Replacement, Knee; Enoxaparin; Hemorrhage; Humans; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Thiazoles; Venous Thromboembolism
PubMed: 33540046
DOI: 10.1016/j.phrs.2021.105438 -
JACC. CardioOncology Sep 2020Many patients with cancer have a hypercoagulable state and an increased risk of developing venous thromboembolism (VTE), arterial occlusion, and pulmonary emboli....
BACKGROUND
Many patients with cancer have a hypercoagulable state and an increased risk of developing venous thromboembolism (VTE), arterial occlusion, and pulmonary emboli. Patients with cancer may also have an increased risk of bleeding with anticoagulant treatment. Recent trials have reported that direct oral anticoagulants (DOACs) are noninferior to the low-molecular-weight heparin, dalteparin, in preventing VTE, but have a higher bleeding rate.
OBJECTIVES
This study compared the efficacy and risks of DOACs versus dalteparin in patients with cancer-related VTEs across all randomized controlled trials (RCTs).
METHODS
This study performed a systematic analysis of RCTs published in PubMed, SCOPUS, and Google Scholar from September 1, 2007 through March 31, 2020 that reported clinical outcomes of treatment with DOACs versus dalteparin in patients with cancer with acute VTE. Two investigators independently performed study selection and data extraction. Extracted data were recorded and exported to statistical software for all analyses (OpenMetaAnalyst).
RESULTS
This study included 4 randomized trials (N = 2,907). Compared with DOACs, dalteparin was associated with higher VTE recurrence (risk ratio [RR]: 1.55; 95% confidence interval [CI]: 1.19 to 2.03; p = 0.001), whereas clinically relevant nonmajor bleeding (CRNMB) was significantly less frequent with dalteparin than that with DOACs (RR: 0.68; 95% CI: 0.54 to 0.86; p = 0.001). The risk of CRNMB was largely observed with patients with gastrointestinal malignancies. No significant differences were observed in major bleeding (RR: 0.74; 95% CI: 0.52 to 1.06; p = 0.11).
CONCLUSIONS
DOACs were noninferior to dalteparin in preventing VTE recurrence in patients with cancer without a significantly increased risk of major bleeding. However, DOACs were associated with higher rates of CRNMB compared with dalteparin, primarily in patients with gastrointestinal malignancies.
PubMed: 34396250
DOI: 10.1016/j.jaccao.2020.06.001 -
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 -
Spinal Cord Aug 2013The objective of this study is to systematically review and estimate the effect of heparin for thromboprophylaxis in patients with acute spinal cord injury (SCI). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The objective of this study is to systematically review and estimate the effect of heparin for thromboprophylaxis in patients with acute spinal cord injury (SCI).
METHODS
We searched the PubMed database up to February 2013. Only randomized control trials (RCTs), quasi-RCTs, cohorts, case-control and cross-sectional studies were included. The incidence of venous thromboembolism (VTE) and major bleeding complication were recorded as the endpoints. The summary relative risks (RR) were calculated by meta-analysis.
RESULTS
A total of 18 studies with 2578 patients were included. Four studies evaluated the effects of low-dose unfractionated heparin (LDUH) compared placebo or untreated. No significant differences were observed, with the summary RR 0.661 (95% confidence interval (CI) 0.365-1.199; Z=1.36, P=0.173) for VTE. Only one RCT compared fixed-dose LDUH with adjusted-dose LDUH, which showed lower VTE incidence but higher bleeding incidence for adjusted dose. Nine trials have compared LDUH with low-molecular-weight heparin (LMWH). No significant differences were observed for VTE with the summary RR 1.633 (95% CI 0.822-3.243; Z=1.40, P=0.162). But major bleeding was lower with LMWH (summary RR=2.034, 95% CI 1.018-4.063; Z=2.01, P=0.044). Three studies compared different LMWHs, which included one for enoxaparin versus tinzaparin and two for enoxaparin versus dalteparin. No significant differences were observed with the summary RR 0.694 (95% CI 0.336-1.434; Z=0.99, P=0.324) for VTE. Three studies compared different dose of LMWH. No differences were observed.
CONCLUSION
Our meta-analysis showed that in patients with acute SCI, LDUH have no thromboprophylaxis effect compared with placebo or untreated; LMWH seems only can reduce bleeding incidence, but not prophylaxis thromboembolism compared with LDUH. Because of no good quality studies existed in this setting, well-designed RCTs are urgently needed.
Topics: Fibrinolytic Agents; Heparin; Humans; PubMed; Randomized Controlled Trials as Topic; Spinal Cord Injuries; Venous Thromboembolism
PubMed: 23689387
DOI: 10.1038/sc.2013.48 -
Cureus Jul 2023Venous thromboembolism (VTE) is a condition often seen in patients diagnosed with cancer and is recognized as a predictor of poor outcomes in these patients. The... (Review)
Review
Venous thromboembolism (VTE) is a condition often seen in patients diagnosed with cancer and is recognized as a predictor of poor outcomes in these patients. The probability of VTE recurring is generally higher in people with cancer than in those without; hence, addressing this issue is essential when making healthcare decisions. Therefore, our systematic review was primarily designed to compare low-weight- molecular heparin (LMWH) to warfarin in reducing recurrent VTE among cancer patients. However, other outcomes were also evaluated, such as mortality and bleeding events observed more in cancer patients. The selection of relevant articles was carried out using a database search and a manual search, which involved reviewing reference lists of articles eligible for inclusion in the current review. The methodological quality of each included study was then assessed using Cochrane's risk of bias tool in the Review Manager software (RevMan 5.4.1). Additionally, pooled results were examined using the Review Manager software and presented as forest plots. Our search of electronic databases elicited a total of 2163 articles, of which only six were deemed eligible for inclusion and analysis. Data pooled from the six studies demonstrated the effectiveness of LMWH in minimizing the reoccurrence of VTE over warfarin [risk ratio (RR): 0.67; 95% CI: 0.47 - 0.95; p = 0.03]. However, LMWH had a similar effect statistically as warfarin on the major bleeding events (RR: 1.05; 95% CI: 0.62 - 1.77; p = 0.85), minor bleeding events (RR: 0.80; 95% CI: 0.54 - 1.20; p = 0.28), and all-cause mortality (RR: 1.00; 95% CI: 0.88 - 1.13; p = 0.99). While LMWH demonstrated its effectiveness in minimizing the incidence of VTE recurrence over warfarin in cancer patients, it had no statistical difference in terms of mortality or bleeding events when compared to warfarin. Based on our findings, we recommend that LMWH continues to be used as a first-line treatment regimen to mitigate recurrent VTE in cancer patients.
PubMed: 37533609
DOI: 10.7759/cureus.41268 -
Life (Basel, Switzerland) Jan 2024This systematic review addresses the crucial role of anticoagulation in microsurgical procedures, focusing on free flap reconstruction and replantation surgeries. The... (Review)
Review
This systematic review addresses the crucial role of anticoagulation in microsurgical procedures, focusing on free flap reconstruction and replantation surgeries. The objective was to balance the prevention of thrombotic complications commonly leading to flap failure, with the risk of increased bleeding complications associated with anticoagulant use. A meticulous PubMed literature search following Evidence-Based-Practice principles yielded 79 relevant articles, including both clinical and animal studies. The full-texts were carefully reviewed and evaluated by the modified Coleman methodology score. Clinical studies revealed diverse perioperative regimens, primarily based on aspirin, heparin, and dextran. Meta-analyses demonstrated similar flap loss rates with heparin or aspirin. High doses of dalteparin or heparin, however, correlated with higher flap loss rates than low dose administration. Use of dextran is not recommended due to severe systemic complications. In animal studies, systemic heparin administration showed predominantly favorable results, while topical application and intraluminal irrigation consistently exhibited significant benefits in flap survival. The insights from this conducted systematic review serve as a foundational pillar towards the establishment of evidence-based guidelines for anticoagulation in microsurgery. An average Coleman score of 55 (maximum 103), indicating low overall study quality, however, emphasizes the need for large multi-institutional, randomized-clinical trials as the next vital step.
PubMed: 38255697
DOI: 10.3390/life14010082 -
Frontiers in Pharmacology 2019Venous thromboembolism (VTE) is a common complication in patients with cancer. Direct oral anticoagulants (DOACs) have been proved to be effective on anticoagulation...
Efficacy and Safety of Direct Oral Anticoagulants for Secondary Prevention of Cancer-Associated Thrombosis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials and Prospective Cohort Studies.
Venous thromboembolism (VTE) is a common complication in patients with cancer. Direct oral anticoagulants (DOACs) have been proved to be effective on anticoagulation therapy in many diseases. However, the efficacy and the safety of DOACs in the secondary prevention of cancer-associated thrombosis (CAT) remain unclear. To assess the value of DOACs in patients with CAT, we performed a systematic review and meta-analysis of randomized controlled trials and prospective cohort studies. Medline, Embase, and the Cochrane Library were searched from their earliest date through to June 2018. Two investigators independently assessed eligibility. Data were extracted by one investigator and verified by the second investigator. The efficacy outcome of this study was recurrent VTE, whereas the safety outcome was major and clinically relevant nonmajor bleeding. Relative risks (RRs) and their corresponding 95% confidence interval (CI) were determined. To pool the results, the Mantel-Haenszel fixed-effects or random-effects models were used. A total of nine articles (six randomized controlled trials and three prospective studies) involving 2,697 patients with CAT who were prescribed DOACs (apixaban, edoxaban, rivaroxaban, or dabigatran) and 2,852 patients who were prescribed traditional anticoagulants [vitamin K antagonists (VKAs), low molecular weight heparin (LMWH), dalteparin, or enoxaparin] were compared. VTE recurrence in the DOAC group was significantly lower than that observed in the traditional anticoagulant group (RR: 0.60; 95%CI: 0.49-0.75; : 0%; < 0.00001). No significant difference in bleeding risk between both groups was found (RR: 0.95; 95%CI: 0.67-1.36; : 75%; = 0.79). Our findings showed that anticoagulant therapy with DOACs may be more effective than traditional anticoagulants to prevent recurrent VTE in patients with CAT, while the safety of DOACs may be equal to that of traditional anticoagulants. These findings support the use of DOACs as the first-line therapy for secondary prevention of CAT in most cancer patients.
PubMed: 31354488
DOI: 10.3389/fphar.2019.00773 -
Current Medical Research and Opinion Mar 2014To conduct a systematic review and mixed-treatment comparison (MTC) meta-analysis to compare the efficacy and safety of low molecular weight heparins (LMWHs) for venous... (Comparative Study)
Comparative Study Meta-Analysis Review
OBJECTIVE
To conduct a systematic review and mixed-treatment comparison (MTC) meta-analysis to compare the efficacy and safety of low molecular weight heparins (LMWHs) for venous thromboembolism (VTE) prophylaxis in hospitalized medically ill patients. As a secondary objective we compared all therapies within the network to each other.
METHODS
We conducted a systematic literature search for randomized trials that evaluated pharmacologic VTE prophylaxis in hospitalized medically ill patients. We conducted a traditional meta-analysis for all pairwise comparisons using a random effects model, reporting relative risks (RRs) and 95% confidence intervals for each outcome. To determine the relative efficacy and safety of included therapies we conducted a MTC meta-analysis using a Bayesian framework, reporting odds ratios (OR) and 95% credible intervals.
RESULTS
Twenty trials met inclusion criteria. Enoxaparin, dalteparin, nadroparin and certoparin were the LMWHs evaluated although none in direct comparative trials. Upon MTC, the relative efficacy of all LMWHs was similar in preventing mortality and VTE as well as in the odds of major and minor bleeding. Dalteparin was not included in the network to evaluate deep vein thrombosis (DVT) and pulmonary embolism (PE) due to lack of reported data and the remaining LMWHs were found to be similar in relative efficacy in preventing these outcomes.
LIMITATIONS
Traditional meta-analysis was not possible for many drug comparisons made within the MTC. Heterogeneity was observed in several of the traditional meta-analyses although this may be an inherent limitation of the studied population. Overall rarity of events contributed to imprecise estimates demonstrated by the wide confidence intervals.
CONCLUSIONS
Enoxaparin, dalteparin, nadroparin and certoparin are similar in relative efficacy for the prevention of mortality and VTE and in the odds of major or minor bleeding while enoxaparin, nadroparin and certoparin are similar in relative efficacy for the prevention of PE and DVT in hospitalized medical patients.
Topics: Bayes Theorem; Heparin, Low-Molecular-Weight; Humans; Venous Thromboembolism
PubMed: 23971722
DOI: 10.1185/03007995.2013.837818