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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 -
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 -
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 -
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 -
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 -
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 -
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 -
Journal of Oncology Pharmacy Practice :... Jan 2019Patients with cancer have an elevated risk of venous thromboembolism. Importantly, patients with cancer, who have metastatic disease, renal insufficiency, or are...
Low-molecular-weight heparins for the prevention of recurrent venous thromboembolism in patients with cancer: A systematic literature review of efficacy and cost-effectiveness.
BACKGROUND
Patients with cancer have an elevated risk of venous thromboembolism. Importantly, patients with cancer, who have metastatic disease, renal insufficiency, or are receiving anticancer therapy, have an even higher risk of a recurrent event. Similarly, the risk of recurrent venous thromboembolism is higher than the risk of an initial event. To reduce the risk, extended duration of prophylaxis for up to six months with low-molecular-weight heparins such as dalteparin, enoxaparin, nadroparin, and tinzaparin is recommended by international guidelines. In this paper, the clinical and economic literature is reviewed to provide evidenced based recommendations based on clinical benefit and economic value.
METHODS
A systematic review of major databases was conducted from January 1996 to October 2016 for randomized controlled trials evaluating the four distinct low-molecular-weight heparins against a vitamin K antagonists control group for the prevention of recurrent venous thromboembolism in patients with active cancer. This was then followed by the application of the National Institute of Health and Clinical Excellence guidance to assess the quality of all trials that met the inclusion criteria. Finally, the cost-effectiveness literature supporting the value proposition of each product was reviewed.
RESULTS
Six randomized trials met the inclusion criteria. There were one, two, and three trials that compared dalteparin, tinzaparin, and enoxaparin to a vitamin K antagonists control group. However, there were no trials for nadroparin in the setting of secondary venous thromboembolism prevention. In addition, only the dalteparin and one of the tinzaparin trials were of high quality and adequately powered. Of the two studies, only the dalteparin trial reported a statistically significant benefit in terms of venous thromboembolism absolute risk reduction when compared to a vitamin K antagonists control group (HR = 0.48; p = 0.002). In addition, there was robust pharmacoeconomic data from Canada, the Netherlands, France, and Austria supporting the cost-effectiveness of dalteparin for this indication. There were no such studies for any of the other agents.
CONCLUSIONS
The totality of high-quality clinical and cost-effectiveness data supports the use of dalteparin over other low-molecular-weight heparins for preventing recurrent venous thromboembolism in patients with cancer.
Topics: Anticoagulants; Cost-Benefit Analysis; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Secondary Prevention; Treatment Outcome; Venous Thromboembolism
PubMed: 28857713
DOI: 10.1177/1078155217727140 -
Taiwanese Journal of Obstetrics &... Jan 2021To assess the roles of the low molecular weight heparin (LMWH) on recurrent pregnancy loss (RPL). The relevant studies of all randomized controlled trials (RCTs) were... (Meta-Analysis)
Meta-Analysis
To assess the roles of the low molecular weight heparin (LMWH) on recurrent pregnancy loss (RPL). The relevant studies of all randomized controlled trials (RCTs) were retrieved, and the systematic evaluation was conducted. PubMed, Embase, and Cochrane library databases were searched by using keywords, including low-molecular-weight heparin or LMWH, and recurrent miscarriage or recurrent pregnancy loss in pregnant women from their earliest data to February 2020. Two investigators independently evaluated eligibility. Risk ratios (RRs) and their corresponding 95% confidence interval (CI) were determined. To pool the results, this meta-analysis was performed using random-effect model due to the high heterogeneity among these eight studies. A total of eight RCTs involving 1854 participants were included in the meta-analysis involving 963 patients with RPL who were prescribed LMWH (enoxaparin, tinzaparin, or dalteparin) alone and 891 patients who were treated with no LMWH interventions (placebo, folic acid or non-treatment) were compared. Pooled data from the remaining eight RCTs showed the differences between intervention groups and control groups. Compared with control groups, LMWH had significantly improved live births (RR,1.19; 95%CI, 1.03 to 1.38; P = 0.02), and reduced miscarriage rates (RR, 0.62; 95%CI, 0.43 to 0.91; P = 0.01). The study suggested that LMWH could improve the live births and reduce the miscarriage rates of RPL. Therefore, LMWH might be a good treatment choice for women with unexplained PRL.
Topics: Abortion, Habitual; Adult; Cardiovascular Agents; Female; Heparin, Low-Molecular-Weight; Humans; Live Birth; Pregnancy; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 33494980
DOI: 10.1016/j.tjog.2020.11.001 -
Medicina (Kaunas, Lithuania) Jan 2024There was an error in the original publication [...].
Correction: Arce-Huamani et al. Efficacy and Safety of Apixaban versus Dalteparin as a Treatment for Cancer-Associated Venous Thromboembolism: A Systematic Review and Meta-Analysis. 2023, , 1867.
There was an error in the original publication [...].
PubMed: 38256435
DOI: 10.3390/medicina60010134