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Pharmacotherapy Dec 2013Major orthopedic surgery is associated with a high risk of venous thromboembolism (VTE). Anticoagulants are recommended to prevent VTE, and recently an oral direct... (Comparative Study)
Comparative Study Meta-Analysis Review
The cost-effectiveness of oral direct factor Xa inhibitors compared with low-molecular-weight heparin for the prevention of venous thromboembolism prophylaxis in total hip or knee replacement surgery.
INTRODUCTION
Major orthopedic surgery is associated with a high risk of venous thromboembolism (VTE). Anticoagulants are recommended to prevent VTE, and recently an oral direct factor Xa inhibitor (FXaI) was approved for this indication. We compared the cost-effectiveness of FXaIs with low-molecular-weight heparin (LMWH) in patients undergoing total hip replacement (THR) or total knee replacement (TKR) surgery.
DESIGN
A decision-tree model was developed to compare the cost-effectiveness of oral direct FXaIs (rivaroxaban, apixaban, and edoxaban) to subcutaneous LMWHs (enoxaparin and dalteparin), with separate models for THR and TKR. The analysis was conducted over a 180-day postoperative time horizon from the U.S. Medicare perspective. The model was developed using TreeAge Pro 2011 (TreeAge Software Inc., Williamstown, MA, USA).
METHODS
Efficacy and safety data (probabilities of distal and proximal deep vein thrombosis, symptomatic pulmonary embolism, and major bleeding) were derived from a systematic review and meta-analysis of phase II and III clinical trials. Costs and quality-adjusted life-years (QALYs) are reported. One-way and probabilistic sensitivity analyses were performed to evaluate parameter uncertainty.
RESULTS
In the THR model, the average costs per patient for FXaIs and LMWHs were $18,762 and $18,897, respectively, and the QALYs were 0.938 and 0.932. In the TKR model, the average cost per patient for FXaIs and LMWHs were $18,804 and $18,991, respectively, and the QALYs were 0.935 and 0.931. In both models, FXaIs dominated LMWH (less costly and more efficacious). Neither model was sensitive to changes in any of the variables in the one-way sensitivity analyses. Probabilistic sensitivity analysis indicated that FXaIs were cost-effective in more than 99% of iterations in the THR population and in 98% of iterations in the TKR population assuming a willingness-to-pay threshold of $50,000/QALY.
CONCLUSION
Oral direct FXaIs may be an economically dominant strategy compared with LMWHs for VTE prophylaxis in patients undergoing either THR or TKR surgery.
Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Cost-Benefit Analysis; Decision Trees; Factor Xa Inhibitors; Heparin, Low-Molecular-Weight; Humans; Medicare; Models, Theoretical; Postoperative Complications; Quality-Adjusted Life Years; United States; Venous Thromboembolism
PubMed: 23625693
DOI: 10.1002/phar.1269 -
Prescrire International Apr 2013Patients with deep venous thrombosis are at a short-term risk of symptomatic or even life-threatening pulmonary embolism, and a long-term risk of post-thrombotic... (Comparative Study)
Comparative Study Review
Patients with deep venous thrombosis are at a short-term risk of symptomatic or even life-threatening pulmonary embolism, and a long-term risk of post-thrombotic syndrome, characterised by lower-limb pain, varicose veins, oedema, and sometimes skin ulcers. What is the best choice of initial antithrombotic therapy following deep venous thrombosis or pulmonary embolism, in terms of mortality and short-term and long-term complications? How do the harm-benefit balances of the different options compare? To answer these questions, we reviewed the available literature using the standard Prescrire methodology. Unfractionated heparin has documented efficacy in reducing mortality and recurrent thromboembolic events in patients with pulmonary embolism or symptomatic proximal (above-knee) deep venous thrombosis. The authors of a systematic review selected 23 trials of low-molecular-weight heparin (LMWH) versus adjusted-dose unfractionated heparin in a total of 9587 patients. Deaths, recurrences and major bleeds were less frequent with LMWH than with unfractionated heparin. The results of other meta-analyses are similar, but all are undermined by a probable publication bias and methodological flaws. Compared to unfractionated heparin, LMWHs have the advantage of fixed-dose administration, once or twice daily, by subcutaneous injection. All available LMWHs seem to have similar efficacy. Those with the longest experience of use are enoxaparin, dalteparin and nadroparin. The harm-benefit balances of fondaparinux and rivaroxaban do not appear more favourable than that of an LMWH followed by an adjusted-dose vitamin K antagonist. A meta-analysis included 12 trials comparing thrombolysis with anticoagulation alone in 700 patients with deep venous thrombosis. Adding a thrombolytic drug did not reduce mortality or the incidence of pulmonary embolism, whereas it increased the incidence of bleeding. A meta-analysis of 13 trials failed to show that adding a thrombolytic drug to initial anticoagulant therapy reduced mortality or recurrences after pulmonary embolism. In the 5 trials that included patients with massive pulmonary embolism, thrombolytic therapy appeared to reduce mortality by about one-half (6% versus 13%). This difference is noteworthy, even if it did not reach the usual threshold of statistical significance. The results of the 6 trials involving patients with deep venous thrombosis, and those of 2 trials and 8 cohort studies in patients with pulmonary embolism at low risk of complications, suggest that outpatient management is acceptable in some cases. Clinical practice guidelines largely agree on the use of LMWH or fondaparinux as initial therapy for most patients with deep venous thrombosis or pulmonary embolism. Unfractionated heparin is generally recommended for patients with renal failure. Thrombolysis is recommended for massive pulmonary embolism and, in some guidelines, for iliofemoral venous thrombosis. In practice, initial treatment of deep venous thrombosis and pulmonary embolism should be based on LMWH in patients without renal failure. Thrombolytic agents may be useful in case of massive pulmonary embolism, but more evaluation is needed. Bleeding and heparin thrombocytopenia are the main adverse effects of these treatments.
Topics: Anticoagulants; Heparin; Heparin, Low-Molecular-Weight; Humans; Practice Guidelines as Topic; Pulmonary Embolism; Secondary Prevention; Venous Thrombosis
PubMed: 23662321
DOI: No ID Found -
Journal of Emergency Nursing Jul 2022The aim of this study was to examine the content, reliability, popularity, and quality of YouTube videos for patients learning how to self-administer subcutaneous low...
BACKGROUND
The aim of this study was to examine the content, reliability, popularity, and quality of YouTube videos for patients learning how to self-administer subcutaneous low molecular weight heparin injections.
METHODS
A systematic review of YouTube videos was conducted on August 20, 2021, using the keywords of "Low-molecular-weight heparin injection," "Enoxaparin injection," "Heparin injection," "Dalteparin injection," and "Tinzaparin injection." Two independent emergency physicians evaluated included videos separately with 5 different score systems (1- Journal of American Medical Association Score, 2-The Video Power Index, 3- Global Quality Scale, 4- Modified 5 Point DISCERN, 5- Total Comprehensiveness Score).
RESULTS
Of 458 videos, a total of 161 unique videos were included. Of these, 94 (58.4%) were classified as useful and 67 (41.6%) as containing misleading information. The total number of views was 6,245,284 in useful information videos. DISCERN score (median 4, P < .001), Global Quality Score (median 4, P < .001), Journal of American Medical Association Score (median 4, P < .001), and Total Comprehensiveness Score (median 6, P < .001) were higher in the Useful Information Group.
CONCLUSIONS
Nurse and physician prescreening and prescoring the accuracy and quality of specific low molecular weight heparin injection self-administration videos before recommending YouTube to patients is warranted. Policies to limit the spread of health misinformation through credibility scoring and evaluation are needed on social media sites such as YouTube.
Topics: Heparin; Heparin, Low-Molecular-Weight; Humans; Information Dissemination; Physicians; Reproducibility of Results; Social Media
PubMed: 35501167
DOI: 10.1016/j.jen.2022.03.007 -
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 -
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 -
The Cochrane Database of Systematic... Feb 2011Compared to patients without cancer, patients with cancer who receive anticoagulant treatment for venous thromboembolism are more likely to develop recurrent venous... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Compared to patients without cancer, patients with cancer who receive anticoagulant treatment for venous thromboembolism are more likely to develop recurrent venous thromboembolism (VTE).
OBJECTIVES
To compare the efficacy and safety of three types of parenteral anticoagulants for the initial treatment of VTE in patients with cancer.
SEARCH STRATEGY
A comprehensive search for studies of anticoagulation in cancer patients including a February 2010 electronic search of: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and ISI Web of Science.
SELECTION CRITERIA
Randomized clinical trials (RCTs) comparing low molecular weight heparin (LMWH), unfractionated heparin (UFH), and fondaparinux in patients with cancer and objectively confirmed VTE.
DATA COLLECTION AND ANALYSIS
Using a standardized data form, data was extracted in duplicate on methodological quality, participants, interventions, and outcomes of interest that included mortality, recurrent VTE, major bleeding, minor bleeding, postphlebitic syndrome, quality of life, and thrombocytopenia.
MAIN RESULTS
Of 3986 identified citations, 16 RCTs were eligible: 13 compared LMWH to UFH, two compared fondaparinux to heparin, and one compared dalteparin to tinzaparin. Meta-analysis of 11 studies showed a statistically significant reduction in mortality at three months of follow up with LMWH compared with UFH (relative risk (RR) 0.71; 95% confidence interval (CI) 0.52 to 0.98). There was little change in the effect estimate after excluding studies of lower methodological quality (RR 0.72; 95% CI 0.52 to 1.00). A meta-analysis of three studies comparing LMWH with UFH showed no statistically significant reduction in VTE recurrence (RR 0.78; 95% CI 0.29 to 2.08). The overall quality of evidence was low for LMWH versus UFH due to imprecision and likely publication bias. There were no statistically significant differences between heparin and fondaparinux for the outcomes of death (RR 1.27; 95% CI 0.88 to 1.84), recurrent VTE (RR 0.95; 95% CI 0.57 to 1.60), major bleeding (RR 0.79; 95% CI 0.39 to1.63) or minor bleeding (RR 1.50; 95% CI 0.87 to 2.59). The one study comparing dalteparin to tinzaparin did not find a statistically significant difference in mortality (RR 0.86; 95% CI 0.43 to 1.73).
AUTHORS' CONCLUSIONS
LMWH is possibly superior to UFH in the initial treatment of VTE in patients with cancer. Additional trials focusing on patient important outcomes will further inform the questions addressed in this review.
Topics: Anticoagulants; Dalteparin; Fibrinolytic Agents; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Polysaccharides; Randomized Controlled Trials as Topic; Tinzaparin; Venous Thromboembolism
PubMed: 21328285
DOI: 10.1002/14651858.CD006649.pub3 -
The Cochrane Database of Systematic... Jan 2008Compared to patients without cancer, patients with cancer receiving anticoagulant treatment for venous thromboembolism are more likely to develop recurrent venous... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Compared to patients without cancer, patients with cancer receiving anticoagulant treatment for venous thromboembolism are more likely to develop recurrent venous thromboembolism (VTE).
OBJECTIVES
To compare the efficacy and safety of three types of anticoagulants (i.e. low molecular weight heparin (LMWH), unfractionated heparin (UFH), and fondaparinux) for the initial treatment of VTE in patients with cancer.
SEARCH STRATEGY
A comprehensive search for studies of anticoagulation in cancer patients including a January 2007 electronic search of : Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and ISI the Web of Science.
SELECTION CRITERIA
Randomized clinical trials (RCTs) comparing LMWH, UFH, and fondaparinux in patients with cancer and objectively confirmed VTE.
DATA COLLECTION AND ANALYSIS
Using a standardized data form data was extracted in duplicate on methodological quality, participants, interventions and outcomes of interest that included all cause mortality, recurrent VTE, major bleeding, minor bleeding, thrombocytopenia and postphlebitic syndrome.
MAIN RESULTS
Of 3986 identified citations, 26 RCTs including cancer patients as subgroups fulfilled the inclusion criteria. Cancer subgroup data was obtained for 15 of the 26 RCTs. Thirteen studies compared a LMWH to UFH while one study compared fondaparinux to UFH and one study compared dalteparin to tinzaparin. Meta-analysis of 11 studies showed a statistically significant mortality reduction in patients treated with LMWH compared with those treated with UFH (Relative risk (RR) = 0.71; 95% confidence interval (CI) 0.52 to 0.98). There was little change in the results after excluding studies of lower methodological quality (RR = 0.72; 95% CI 0.52 to 1.00). A meta-analysis of three studies comparing LMWH with UFH in reducing recurrent VTE was inconclusive (RR = 0.78; 95% CI 0.29 to 2.08). No data was available for bleeding outcomes, thrombocytopenia or postphlebitic syndrome. Compared to UFH, fondaparinux showed a non-statistically significant benefit for the outcome of death (RR = 0.52; 95% CI 0.26 to 1.05). The one study comparing dalteparin to tinzaparin showed a non-statistically significant mortality reduction with dalteparin (RR = 0.86; 95% CI 0.43 to 1.73).
AUTHORS' CONCLUSIONS
Based on the included trials, LMWH is likely to be superior to UFH in the initial treatment of VTE in patients with cancer. However, there is a need for more trials to better address this research question in cancer patients. Moreover, researchers should consider making the raw data of RCTs available for individual patient data meta-analyses.
Topics: Anticoagulants; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Polysaccharides; Randomized Controlled Trials as Topic; Venous Thromboembolism
PubMed: 18254108
DOI: 10.1002/14651858.CD006649.pub2 -
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 -
Mayo Clinic Proceedings Dec 2019To explore the efficacy and safety of direct oral factor Xa inhibitors in the treatment of cancer-associated acute venous thromboembolism (VTE). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To explore the efficacy and safety of direct oral factor Xa inhibitors in the treatment of cancer-associated acute venous thromboembolism (VTE).
PATIENTS AND METHODS
MEDLINE, CENTRAL (Cochrane Central Register of Controlled Trials), and Embase databases were searched for trials comparing direct oral anticoagulants (DOACs) to dalteparin for the management of cancer-associated acute VTE. Databases were searched from inception to September 19, 2018. A network meta-analysis using both frequentist and Bayesian methods was performed to analyze VTE recurrence and major and clinically relevant nonmajor bleeding.
RESULTS
We identified 3 randomized controlled trials, at low risk of bias, that enrolled 1739 patients with cancer-associated VTE. Direct comparison revealed a lower rate of VTE recurrence in DOAC compared with dalteparin groups (odds ratio [OR], 0.48; 95% CI, 0.24-0.96; I=46%). Indirect comparison suggested that apixaban had greater reduction in VTE recurrence compared with dalteparin (OR, 0.10; 95% CI, 0.01-0.82) but not rivaroxaban or edoxaban. Apixaban also had the highest probability of being ranked most effective. By direct comparisons, there was an increased likelihood of major bleeding in the DOAC group compared with dalteparin (OR, 1.70; 95% CI, 1.04-2.78). Clinically relevant nonmajor bleeding did not differ. Indirect estimates were imprecise. Subgroup analyses in gastrointestinal cancers suggested that dalteparin may have the lowest risk of bleeding, whereas estimates in urothelial cancer were imprecise.
CONCLUSION
Direct oral anticoagulants appear to lower the risk of VTE recurrence compared with dalteparin while increasing major bleeding. Apixaban may be associated with the lowest risk of VTE recurrence compared with the other DOACs.
Topics: Administration, Oral; Factor Xa Inhibitors; Humans; Neoplasms; Venous Thromboembolism
PubMed: 31685262
DOI: 10.1016/j.mayocp.2019.05.035