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European Journal of Clinical... Aug 2015Although therapeutic dosages of most low-molecular-weight heparins (LMWHs) are known to accumulate in patients with renal insufficiency, for the lower prophylactic... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Although therapeutic dosages of most low-molecular-weight heparins (LMWHs) are known to accumulate in patients with renal insufficiency, for the lower prophylactic dosages this has not been clearly proven. Nevertheless, dose reduction is often recommended. We conducted a systematic review to investigate whether prophylactic dosages of LMWH accumulate in renal insufficient patients.
METHODS
A comprehensive search was conducted on 17 February 2015 using Embase, Medline, Web of Science, Scopus, Cochrane, PubMed publisher, and Google scholar. The syntax emphasized for LMWHs, impaired renal function, and pharmacokinetics. The search yielded 674 publications. After exclusion by reading the titles, abstracts, and if necessary the full paper, 11 publications remained.
RESULTS
For dalteparin and tinzaparin, no accumulation was observed. Enoxaparin, on the other hand, did lead to accumulation in patients with renal insufficiency, although not in patients undergoing renal replacement therapy. Bemiparin and certoparin also did show accumulation. No data were available for nadroparin.
CONCLUSIONS
In this systematic review, we show that prophylactic dosages of tinzaparin and dalteparin are likely to be safe in patients with renal insufficiency and do not need dose reduction based on the absence of accumulation. However, prophylactic dosages of enoxaparin, bemiparin, and certoparin did show accumulation in patients with a creatinine clearance (CrCl) below 30 ml/min, and therefore, dose reduction is required. The differences in occurrence of accumulation seem to depend on the mean molecular weight of LMWHs.
Topics: Anticoagulants; Heparin, Low-Molecular-Weight; Humans; Renal Insufficiency; Venous Thrombosis
PubMed: 26071276
DOI: 10.1007/s00228-015-1880-5 -
Mayo Clinic Proceedings Feb 2022To maintain living, interactive evidence (LIvE) on the benefits and harms of different treatment options in adults with cancer-associated thrombosis (CAT). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To maintain living, interactive evidence (LIvE) on the benefits and harms of different treatment options in adults with cancer-associated thrombosis (CAT).
METHODS
We have used a novel LIvE synthesis framework to maintain this living, interactive systematic review since September 19, 2018. Randomized controlled trials evaluating the efficacy and safety of direct oral anticoagulants (DOACs) compared with low-molecular-weight heparin for CAT are included in this analysis. Details of LIvE synthesis framework are available at the website https://cat.network-meta-analysis.com.
RESULTS
The results are constantly updated as new information becomes available (https://cat.network-meta-analysis.com/CAT.html). The living, interactive systematic review currently includes 4 randomized controlled trials (N=2894). Direct comparisons show that DOACs significantly decrease recurrent venous thromboembolism (VTE) events compared with dalteparin (odds ratio [OR], 0.59; 95% CI, 0.41 to 0.86; I, 25%) without significantly increasing major bleeding (OR, 1.34; 95% CI, 0.83 to 2.18; I, 28%). Mixed treatment comparisons show that apixaban (OR, 0.41; 95% credible interval [CrI], 0.16 to 0.95) and rivaroxaban (OR, 0.58; 95% CrI, 0.37 to 0.90) significantly decrease VTE recurrent events compared with dalteparin. Edoxaban significantly increases major bleeding compared with dalteparin (OR, 1.73; 95% CrI, 1.04 to 3.16), and rivaroxaban significantly increases clinically relevant nonmajor bleeding compared with dalteparin and other DOACs. There are no significant differences between DOACs in terms of VTE recurrences and major bleeding.
CONCLUSION
DOACs should be considered a standard of care for the treatment of CAT except in patients with a high risk of bleeding. Current evidence favors the use of apixaban for the treatment of CAT among other DOACs.
REGISTRATION
Open Science Framework (https://osf.io/dth86).
Topics: Administration, Oral; Anticoagulants; Dalteparin; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Network Meta-Analysis; Venous Thromboembolism
PubMed: 34172290
DOI: 10.1016/j.mayocp.2020.10.041 -
Journal of Cardiovascular Pharmacology... May 2017Venous thromboembolism (VTE) is a common complication that manifests during and/or after hospitalization, as well as postsurgeries including orthopedic surgeries.... (Review)
Review
BACKGROUND
Venous thromboembolism (VTE) is a common complication that manifests during and/or after hospitalization, as well as postsurgeries including orthopedic surgeries. Edoxaban is a new oral direct factor Xa inhibitor that has been recently approved for treating VTE in patients who have already been treated with a parenteral anticoagulant and for the prevention of stroke and non-central nervous system systemic embolism in patients with nonvalvular atrial fibrillation.
OBJECTIVES
The purpose of this systematic review was to evaluate the safety and efficacy of edoxaban for VTE prophylaxis after lower limb orthopedic surgery.
MATERIALS AND METHODS
A comprehensive search was conducted in Google Scholar, PubMed, MEDLINE, and ScienceDirect to identify potential records, then titles, abstracts, and full texts were screened using the inclusion criteria to filter out irrelevant studies. Moreover, the data extraction and quality assessment were undertaken using standardized tools, and the results were narratively synthesized and presented in tables.
RESULTS
Six studies were included in this systematic review after screening 2989 records. The majority of studies demonstrated a statistically significant reduction in VTE events in the edoxaban group(s) compared to the dalteparin, placebo, or enoxaparin groups (P < .05). The differences in VTE cases in some studies reached to approximately 50% favoring edoxaban 30 mg over the comparator (P < .05). However, other studies uncovered a statistically insignificant difference between edoxaban and the comparator "enoxaparin" when used for VTE prophylaxis (P > .05). On the other hand, although edoxaban found to cause more bleeding, the differences between edoxaban and the comparator are statistically insignificant (P > .05).
CONCLUSION
This study helped to amalgamate evidence with regard to the use of edoxaban for VTE prophylaxis post-lower limb orthopedic surgery. In line with the results of the reviewed studies, edoxaban seems to be highly effective in reducing VTE post-lower limb orthopedic surgery.
Topics: Administration, Oral; Drug Administration Schedule; Factor Xa Inhibitors; Hemorrhage; Humans; Orthopedic Procedures; Patient Safety; Pyridines; Risk Factors; Thiazoles; Treatment Outcome; Venous Thromboembolism
PubMed: 27811198
DOI: 10.1177/1074248416675732 -
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 -
Low-molecular-weight heparins for managing vaso-occlusive crises in people with sickle cell disease.The Cochrane Database of Systematic... Dec 2015Sickle cell disease is one of the most common and severe genetic disorders in the world. It can be broadly divided into two distinct clinical phenotypes characterized by... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Sickle cell disease is one of the most common and severe genetic disorders in the world. It can be broadly divided into two distinct clinical phenotypes characterized by either haemolysis or vaso-occlusion. Pain is the most prominent symptom of vaso-occlusion, and hypercoagulability is a well-established pathogenic phenomenon in people with sickle cell disease. Low-molecular-weight heparins might control this hypercoagulable state through their anticoagulant effect. This is an update of a previously published version of this review.
OBJECTIVES
To assess the effects of low-molecular-weight heparins for managing vaso-occlusive crises in people with sickle cell disease.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register comprising references identified from comprehensive electronic database searches. We also searched abstract books of conference proceedings and several online trials registries for ongoing trials.Date of the last search of the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register: 28 September 2015.
SELECTION CRITERIA
Randomised controlled clinical trials and controlled clinical trials that assessed the effects of low-molecular-weight heparins in the management of vaso-occlusive crises in people with sickle cell disease.
DATA COLLECTION AND ANALYSIS
Study selection, data extraction, assessment of risk of bias and analyses were carried out independently by the two review authors.
MAIN RESULTS
Two studies comprising 287 participants were included. One study (with an overall unclear to high risk of bias) involved 253 participants and the quality of the evidence for most outcomes was very low. This study, reported that pain severity at day two and day three was lower in the tinzaparin group than in the placebo group (P < 0.01, analysis of variance (ANOVA)) and additionally at day 4 (P < 0.05 (ANOVA)). Thus tinzaparin resulted in more rapid resolution of pain, as measured with a numerical pain scale. The mean difference in duration of painful crises was statistically significant at -1.78 days in favour of the tinzaparin group (95% confidence interval -1.94 to -1.62). Participants treated with tinzaparin had statistically significantly fewer hospitalisation days than participants in the group treated with placebo, with a mean difference of -4.98 days (95% confidence interval -5.48 to -4.48). Two minor bleeding events were reported as adverse events in the tinzaparin group, and none were reported in the placebo group. The second study (unclear risk of bias) including 34 participants and was a conference abstract with limited data and only addressed one of the predefined outcomes of the review; i.e. pain intensity. After one day pain intensity reduced more, as reported on a visual analogue scale, in the dalteparin group than in the placebo group, mean difference -1.30 (95% confidence interval -1.60 to -1.00), with the quality of evidence rated very low. The most important reasons for downgrading the quality of evidence were serious risk of bias and imprecision (due to low sample size or low occurrence of events).
AUTHORS' CONCLUSIONS
Based on the results of two studies, evidence is incomplete to support or refute the effectiveness of low-molecular-weight heparins in people with sickle cell disease. Vaso-occlusive crises are extremely debilitating for sufferers of sickle cell disease; therefore well-designed placebo-controlled studies with other types of low-molecular-weight heparins, and in participants with different genotypes of sickle cell disease, still need to be carried out to confirm or dismiss the results of this single study.
Topics: Anemia, Sickle Cell; Anticoagulants; Dalteparin; Heparin, Low-Molecular-Weight; Humans; Pain Measurement; Peripheral Vascular Diseases; Randomized Controlled Trials as Topic; Tinzaparin
PubMed: 26684281
DOI: 10.1002/14651858.CD010155.pub3 -
PharmacoEconomics May 2017Total hip replacement (THR) and total knee replacement (TKR) surgeries are being performed with increasing regularity and are associated with a high risk of developing a... (Comparative Study)
Comparative Study Review
BACKGROUND
Total hip replacement (THR) and total knee replacement (TKR) surgeries are being performed with increasing regularity and are associated with a high risk of developing a venous thromboembolism (VTE). New oral anticoagulants (NOACs) may be more effective at preventing VTEs but are associated with more bleeding events versus traditional anticoagulants.
OBJECTIVE
The objective of this systematic review was to identify published economic analyses of NOACs for primary VTE prophylaxis following THR and TKR surgeries, and to summarise the modelling techniques used and the cost-effectiveness results.
METHODS
Electronic searches of MEDLINE, EconLit and The Cochrane Library were performed from January 2008 to February 2015. Reference lists of included articles and reviews were examined for relevant studies.
RESULTS
Sixteen relevant economic analyses were identified, all of which used decision-tree structures to model acute events after surgery; 13 included a chronic-phase Markov module to capture long-term complications of VTE and recurrent VTE events. All studies included prophylaxis-related major bleeding events and captured both symptomatic and asymptomatic VTE-related events; nine studies distinguished between distal and proximal deep vein thrombosis events. Overall, rivaroxaban dominated enoxaparin in eight of 11 studies and dalteparin in one study, dabigatran dominated enoxaparin in five of seven studies and apixaban dominated enoxaparin in two of two studies. Rivaroxaban dominated dabigatran in four of four studies, apixaban dominated dabigatran in two of two studies and rivaroxaban dominated apixaban in one study.
CONCLUSIONS
The economic analyses showed reasonable consistency in the model structures used and the events captured. The results strongly suggested that NOACs are cost effective alternatives to low molecular-weight heparin. Dabigatran appeared to be the least cost effective NOAC. More research is needed to assess the cost effectiveness of apixaban and edoxaban.
Topics: Administration, Oral; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Cost-Benefit Analysis; Decision Trees; Humans; Markov Chains; Models, Economic; Venous Thromboembolism
PubMed: 28185212
DOI: 10.1007/s40273-017-0486-4 -
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 -
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 -
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