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Journal of Thrombosis and Haemostasis :... Jul 2017Essentials Hemorrhagic risk of antiplatelet drugs is generally thought to be lower than anticoagulants. We systematically reviewed trials comparing antiplatelet and... (Meta-Analysis)
Meta-Analysis Review
UNLABELLED
Essentials Hemorrhagic risk of antiplatelet drugs is generally thought to be lower than anticoagulants. We systematically reviewed trials comparing antiplatelet and anticoagulant drugs in older patients. Overall, the risk of major bleeding was similar with antiplatelet and with anticoagulant drugs. In elderly patients, risks and benefits of antiplatelet drugs should be carefully weighted.
SUMMARY
Background The hemorrhagic risk of antiplatelet drugs in older patients could be higher than is usually assumed. Objective To compare the bleeding risk of antiplatelet drugs and oral anticoagulants in elderly patients. Methods We carried out a systematic review and meta-analysis. We searched PubMed, EMBASE and the Cochrane Library up to January 2016 for randomized and non-randomized controlled trials (RCTs) and parallel cohorts comparing antiplatelet drugs and oral anticoagulants in patients aged 65 years or older. Two independent authors assessed studies for inclusion. The pooled relative risk (RR) of major bleeding was estimated using a random model. Results Seven RCTs (4550 patients) and four cohort studies (38 649 patients) met the inclusion criteria. The risk of major bleeding when on aspirin or clopidogrel was equal to that when on warfarin in RCTs (RR, 1.01; 95% confidence interval (95% CI), 0.69-1.48; moderate-quality evidence), lower than when on warfarin in non-randomized cohort studies (RR, 0.87; 95% CI, 0.77-0.99; low-quality evidence) and not different when all studies were combined (RR, 0.86; 95% CI, 0.73-1.01). Bleeding of any severity (RR, 0.70; 95% CI, 0.57-0.86) and intracranial bleeding (RR, 0.46; 95% CI, 0.30-0.73) were less frequent with antiplatelet drugs than with warfarin. All-cause mortality was similar (RR, 0.99). Subgroup analysis suggested that major bleeding might be higher with warfarin than with aspirin in patients over 80 years old. Conclusion Elderly patients treated with aspirin or clopidogrel suffer less any-severity bleeding but have a risk of major bleeding similar to that of oral anticoagulants, with the exception of intracranial bleeding.
Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Clopidogrel; Cohort Studies; Female; Hemorrhage; Humans; Intracranial Hemorrhages; Male; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Risk; Stroke; Ticlopidine; Treatment Outcome; Vitamin K; Warfarin
PubMed: 28393461
DOI: 10.1111/jth.13697 -
Neuroepidemiology 2024Current evidence regarding the clinical outcomes of non-vitamin K oral anticoagulants (NOACs) versus warfarin in patients with atrial fibrillation (AF) and previous... (Meta-Analysis)
Meta-Analysis
Effectiveness and Safety of Non-Vitamin K Oral Anticoagulants versus Warfarin in Patients with Atrial Fibrillation and Previous Stroke: A Systematic Review and Meta-Analysis.
INTRODUCTION
Current evidence regarding the clinical outcomes of non-vitamin K oral anticoagulants (NOACs) versus warfarin in patients with atrial fibrillation (AF) and previous stroke is inconclusive, especially in patients with previous intracranial haemorrhage (ICrH). We aim to undertake a systematic review and meta-analysis assessing the effectiveness and safety of NOACs versus warfarin in AF patients with a history of stroke.
METHODS
We searched studies published up to December 10, 2022, on PubMed, Medline, Embase, and Cochrane Central Register of Controlled Trials. Studies on adults with AF and previous ischaemic stroke (IS) or IrCH receiving either NOACs or warfarin and capturing outcome events (thromboembolic events, ICrH, and all-cause mortality) were eligible for inclusion.
RESULTS
Six randomized controlled trials (RCTs) (including 19,489 patients with previous IS) and fifteen observational studies (including 132,575 patients with previous IS and 13,068 patients with previous ICrH) were included. RCT data showed that compared with warfarin, NOACs were associated with a significant reduction in thromboembolic events (odds ratio [OR]: 0.85, 95% confidence interval [CI]: 0.75-0.96), ICrH (OR: 0.57, 95% CI: 0.36-0.90), and all-cause mortality (OR: 0.88, 95% CI: 0.80-0.98). In analysing observational studies, similar results were retrieved. Moreover, patients with previous ICrH had a lower OR on thromboembolic events than those with IS (OR: 0.66, 95% CI: 0.46-0.95 vs. OR: 0.80, 95% CI: 0.70-0.93) in the comparison between NOACs and warfarin.
CONCLUSIONS
Observational data showed that in AF patients with previous stroke, NOACs showed better clinical performance compared to warfarin and the benefits of NOACs were more pronounced in patients with previous IrCH versus those with IS. RCT data also showed NOACs are superior to warfarin. However, current RCTs only included AF patients who survived an IS, and further large RCTs focused on patients with previous ICrH are warranted.
Topics: Adult; Humans; Warfarin; Atrial Fibrillation; Vitamin K; Anticoagulants; Stroke; Intracranial Hemorrhages; Thromboembolism; Ischemic Stroke; Treatment Outcome
PubMed: 37848006
DOI: 10.1159/000534596 -
Farmacia Hospitalaria : Organo Oficial... 2011The administration of vitamin K immediately after birth has shown a significant decrease in the incidence of newborn bleeding, but there is not enough evidence to... (Review)
Review
BACKGROUND
The administration of vitamin K immediately after birth has shown a significant decrease in the incidence of newborn bleeding, but there is not enough evidence to determine the most appropriate method of administration. The objective of this review is to determine the effectiveness of orally administered vitamin K compared to the intramuscular route in the prevention of hemorrhagic disease of newborn (HDN).
METHODS
We conducted a systematic review of the main databases (Medline, Embase and Cochrane, among others) without limitation by date, language or type of study. Selected studies evaluated the efficacy and safety of vitamin K. Excluded were studies in pregnant women in preterm infants or patients with pathology. The validity of these studies was assessed by CASPe tools for systematic reviews and clinical trials.
RESULTS
Only two studies evaluated clinical aspects. They showed a reduction in the incidence of bleeding in the newborn after intramuscular prophylaxis with vitamin K. With regard to the oral route, different studies examined the effectiveness of vitamin K by determining biochemical parameters (factor X, prothrombin time and index, vitamin K1 in plasma and prothrombin antigen, among others) with inconclusive results regarding the route of administration and the number of doses.
CONCLUSIONS
There is sufficient evidence to support the effectiveness of a single intramuscular dose of vitamin K to prevent the classic form of HDN. With regard to late HDN and oral route, the results are inconclusive because the studies used biochemical indicators of effectiveness, which can not be correlated with the actual coagulation status of the newborn due to lack of scientific evidence.
Topics: Humans; Infant, Newborn; Vitamin K; Vitamin K Deficiency Bleeding; Vitamins
PubMed: 21111646
DOI: 10.1016/j.farma.2010.09.001 -
The Cochrane Database of Systematic... 2000Vitamin K deficiency can cause bleeding in an infant in the first weeks of life. This is known as Hemorrhagic Disease of the Newborn (HDN). HDN is divided into three... (Review)
Review
BACKGROUND
Vitamin K deficiency can cause bleeding in an infant in the first weeks of life. This is known as Hemorrhagic Disease of the Newborn (HDN). HDN is divided into three categories: early, classic and late HDN. Early HDN occurs within 24 hours post partum and falls outside the scope of this review. Classic HDN occurs on days one to seven; common bleeding sites are gastrointestinal, cutaneous, nasal and from a circumcision. Late HDN occurs from week 2-12; the most common bleeding sites are intracranial, cutaneous, and gastrointestinal. Vitamin K is commonly given prophylactically after birth for the prevention of HDN, but the preferred route is uncertain.
OBJECTIVES
To review the evidence from randomized trials in order to determine the effectiveness of vitamin K prophylaxis in the prevention of classic and late HDN. Main questions are: Is one dose of vitamin K, given after birth, able to significantly reduce the incidence of classic and late HDN? Is there a significant difference between the oral route and the intramuscular route in preventing classic and late HDN? Are multiple oral doses of vitamin K, given after birth, able to significantly reduce the incidence of classic and late HDN?
SEARCH STRATEGY
The standard search strategy of the Cochrane Neonatal Review Group was used.
SELECTION CRITERIA
All trials using random or quasi-random patient allocation, in which methods of vitamin K prophylaxis in infants were compared to each other, placebo or no treatment, were included.
DATA COLLECTION AND ANALYSIS
Data were extracted independently by each author and were analysed with the standard methods of the Cochrane Collaboration and its Neonatal Review Group, using relative risk, risk difference and weighted mean difference.
MAIN RESULTS
Two eligible randomized trials, each comparing a single dose of intramuscular vitamin K with placebo or nothing, assessed effect on clinical bleeding. One dose of vitamin K reduced clinical bleeding at 1-7 days, including bleeding after circumcision, and improved biochemical indices of coagulation status. Eleven additional eligible randomized trials compared either a single oral dose of vitamin K with placebo or nothing, a single oral with a single intramuscular dose of vitamin K, or three oral doses with a single intramuscular dose. None of these trials assessed clinical bleeding. Oral vitamin K improved biochemical indices of coagulation status at 1-7 days. There was no evidence of a difference between the oral and intramuscular route in effects on biochemical indices of coagulation status. A single oral compared with a single intramuscular dose resulted in lower plasma vitamin K levels at two weeks and one month, whereas a 3-dose oral schedule resulted in higher plasma vitamin K levels at two weeks and at two months than did a single intramuscular dose.
REVIEWER'S CONCLUSIONS
A single dose (1.0 mg) of intramuscular vitamin K after birth is effective in the prevention of classic HDN. Either intramuscular or oral (1.0 mg) vitamin K prophylaxis improves biochemical indices of coagulation status at 1-7 days. Neither intramuscular nor oral vitamin K has been tested in randomized trials with respect to effect on late HDN. Oral vitamin K, either single or multiple dose, has not been tested in randomized trials for its effect on either classic or late HDN.
Topics: Humans; Infant, Newborn; Infant, Premature; Randomized Controlled Trials as Topic; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding
PubMed: 11034761
DOI: 10.1002/14651858.CD002776 -
The Cochrane Database of Systematic... Sep 2012People who have had a transient ischaemic attack (TIA) or non-disabling ischaemic stroke have an annual risk of major vascular events of between 4% and 11%. Aspirin... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
People who have had a transient ischaemic attack (TIA) or non-disabling ischaemic stroke have an annual risk of major vascular events of between 4% and 11%. Aspirin reduces this risk by 20% at most. Secondary prevention trials after myocardial infarction indicate that treatment with vitamin K antagonists is associated with a risk reduction approximately twice that of treatment with antiplatelet therapy.
OBJECTIVES
To compare the efficacy and safety of vitamin K antagonists and antiplatelet therapy in the secondary prevention of vascular events after cerebral ischaemia of presumed arterial origin.
SEARCH METHODS
We searched the Cochrane Stroke Group Trials Register (last searched 15 September 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 3), MEDLINE (2008 to September 2011) and EMBASE (2008 to September 2011). In an effort to identify further relevant trials we searched ongoing trials registers and reference lists. We also contacted authors of published trials for further information and unpublished data.
SELECTION CRITERIA
Randomised trials of oral anticoagulant therapy with vitamin K antagonists (warfarin, phenprocoumon or acenocoumarol) versus antiplatelet therapy for long-term secondary prevention after recent transient ischaemic attack or minor ischaemic stroke of presumed arterial origin.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials, assessed trial quality and extracted data.
MAIN RESULTS
We included eight trials with a total of 5762 participants. The data showed that anticoagulants (in any intensity) are not more efficacious in the prevention of vascular events than antiplatelet therapy (medium intensity anticoagulation: relative risk (RR) 0.80, 95% confidence interval (CI) 0.56 to 1.14; high intensity anticoagulation: RR 1.02, 95% CI 0.49 to 2.13). There is no evidence that treatment with low intensity anticoagulation gives a higher bleeding risk than treatment with antiplatelet agents: RR 1.27 (95% CI 0.79 to 2.03). However, it was clear that medium and high intensity anticoagulation with vitamin K antagonists, with an INR of 2.0 to 4.5, were not safe because they yielded a higher risk of major bleeding complications (medium intensity anticoagulation: RR 1.93, 95% CI 1.27 to 2.94; high intensity anticoagulation: RR 9.0, 95% CI 3.9 to 21).
AUTHORS' CONCLUSIONS
For the secondary prevention of further vascular events after TIA or minor stroke of presumed arterial origin, there is sufficient evidence to conclude that vitamin K antagonists in any dose are not more efficacious than antiplatelet therapy and that medium and high intensity anticoagulation leads to a significant increase in major bleeding complications.
Topics: Administration, Oral; Anticoagulants; Cause of Death; Hemorrhage; Humans; International Normalized Ratio; Ischemic Attack, Transient; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Secondary Prevention; Stroke; Vitamin K
PubMed: 22972051
DOI: 10.1002/14651858.CD001342.pub3 -
Journal of Thrombosis and Haemostasis :... Sep 2014Although warfarin and other vitamin K antagonists (VKAs) are the most widely used oral anticoagulants for the prevention and treatment of thromboembolic events, a number... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Although warfarin and other vitamin K antagonists (VKAs) are the most widely used oral anticoagulants for the prevention and treatment of thromboembolic events, a number of factors hamper their manageability, the most important being the inter-individual variability of the therapeutic dose requirement. Following the discovery of the influence of CYP2C9 and VKORC1 polymorphisms on VKA dose requirements, there has been interest in genotype-guided VKA dosing in order to reduce the risk of over-anticoagulation at the time of therapy initiation and hence the risk of bleeding, particularly prominent during the early days of treatment. To assess the impact on clinical outcomes of pharmacogenetic testing for initial VKA dosing, we have performed a systematic review and meta-analysis of the literature.
METHODS
MEDLINE, EMBASE and Cochrane databases were searched up to March 2014. Only randomized controlled trials comparing genotype-guided vs. clinically-guided warfarin dosing were included.
RESULTS
Nine trials including 2812 patients met the inclusion criteria and were pooled for meta-analytical evaluation. Risk of bias, assessed according to the Cochrane methodology, showed a low risk for the majority of domains analyzed in the included trials. A statistically significant reduction in the risk ratio (RR) for developing major bleeding events was observed in the pharmacogenetic-guided group compared with the control group (RR = 0.47; 95% CI, 0.23-0.96; P = 0.040).
CONCLUSIONS
The results of this meta-analysis show that genotype-guided initial VKA dosing is able to reduce serious bleeding events by approximately 50% compared with clinically-guided dosing approaches.
Topics: Adult; Aged; Anticoagulants; Blood Coagulation; Cytochrome P-450 CYP2C9; Female; Genotype; Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Pharmacogenetics; Prospective Studies; Randomized Controlled Trials as Topic; Reproducibility of Results; Thromboembolism; Treatment Outcome; Vitamin K; Vitamin K Epoxide Reductases; Warfarin
PubMed: 25040440
DOI: 10.1111/jth.12647 -
Health Technology Assessment... Sep 2009To determine the clinical and cost-effectiveness of vitamin K in preventing osteoporotic fractures in postmenopausal women. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To determine the clinical and cost-effectiveness of vitamin K in preventing osteoporotic fractures in postmenopausal women.
DATA SOURCES
Searches were conducted in May 2007 in MEDLINE, MEDLINE In-Process, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, BIOSIS, CINAHL, DARE, NHS EED and HTA databases, AMED, NRR, Science Citation Index and Current Controlled Trials. The MEDLINE search was updated in March 2009.
REVIEW METHODS
Selected studies were assessed and subjected to data extraction and quality assessment using standard methods. Where appropriate, meta-analysis was carried out. A mathematical model was constructed to estimate the cost-effectiveness of vitamin K1.
RESULTS
The electronic literature searches identified 1078 potentially relevant articles. Of these, 14 articles relating to five trials that compared vitamin K with a relevant comparator in postmenopausal women with osteoporosis or osteopenia met the review inclusion criteria. The double-blind ECKO trial compared 5 mg of phylloquinone (vitamin K1) with placebo in Canadian women with osteopenia but without osteoporosis. Four open-label trials used 45 mg of menatetrenone (vitamin K2) in Japanese women with osteoporosis; the comparators were no treatment, etidronate or calcium. The methodological quality of the ECKO trial was good; however, all four menatetrenone trials were poorly reported and three were very small (n < 100 in each group). Phylloquinone was associated with a statistically significant reduction in the risk of clinical fractures relative to placebo [relative risk 0.46, 95% confidence interval (CI) 0.22 to 0.99]; morphometric vertebral fractures were not reported. The smaller menatetrenone trials found that menatetrenone was associated with a reduced risk of morphometric vertebral fractures relative to no treatment or calcium; however, the larger Osteoporosis Fracture (OF) study found no evidence of a reduction in vertebral fracture risk. The three smaller trials found no significant difference between treatment groups in non-vertebral fracture incidence. In the ECKO trial, phylloquinone was not associated with an increase in adverse events. In the menatetrenone trials, adverse event reporting was generally poor; however, in the OF study, menatetrenone was associated with a significantly higher incidence of skin and skin appendage lesions. No published economic evaluations of vitamin K were found and a mathematical model was thus constructed to estimate the cost-effectiveness of vitamin K1. Comparators were alendronate, risedronate and strontium ranelate. Vitamin K1 and alendronate were markedly more cost-effective than either risedronate or strontium ranelate. The base-case results favoured vitamin K1, but this relied on many assumptions, particularly on the efficacy of preventing hip and vertebral fractures. Calculation of the expected value of sampled information was conducted assuming a randomised controlled trial of 5 years' duration comparing alendronate with vitamin K1. The costs incurred in obtaining updated efficacy data from a trial with 2000 women per arm were estimated to be a cost-effective use of resources.
CONCLUSIONS
There is currently large uncertainty over whether vitamin K1 is more cost-effective than alendronate; further research is required. It is unlikely that the present prescribing policy (i.e. alendronate as first-line treatment) would be altered.
Topics: Aged; Aged, 80 and over; Bone Density Conservation Agents; Cost-Benefit Analysis; Female; Fractures, Bone; Humans; Models, Econometric; Osteoporosis, Postmenopausal; Quality-Adjusted Life Years; Vitamin K; Vitamin K 1; Vitamin K 2; Vitamins
PubMed: 19818211
DOI: 10.3310/hta13450 -
European Review For Medical and... Aug 2021To compare the outcomes between direct-acting oral anticoagulants and vitamin K antagonists, particularly for risk of stroke and bleeding, among patients with atrial... (Comparative Study)
Comparative Study Meta-Analysis
Comparison of outcomes of direct-acting oral anticoagulants vs. vitamin K antagonists in patients with bioprosthetic heart valves or valve repair: a systematic review and meta-analysis.
OBJECTIVE
To compare the outcomes between direct-acting oral anticoagulants and vitamin K antagonists, particularly for risk of stroke and bleeding, among patients with atrial fibrillation (AF) and bioprosthetic heart valve replacement or repair.
MATERIALS AND METHODS
A systematic search was conducted in the PubMed, Scopus, Cochrane Database of Systematic Reviews and Google scholar databases. Studies that were done in patients with AF who underwent bioprosthetic heart valve replacement or repair and that compared the outcomes between the use of direct-acting oral anticoagulants (DOACs) and vitamin K antagonists were eligible for inclusion. Studies that were preferably randomized controlled trials or adopted a cohort approach or retrospective data-based studies were considered for inclusion. The strength of association was presented in the form of pooled hazards risk (HR). Statistical analysis was done using STATA version 16.0.
RESULTS
A total of 8 articles were included in the meta-analysis. There were no significant differences in the risk of "all-cause stroke" [HR 0.72, 95% CI: 0.39, 1.34] and ischemic stroke [HR 0.79, 95% CI: 0.49, 1.29] between the two groups. The risk of "any bleeding" [HR 0.74, 95% CI: 0.64, 0.87], major bleeding [HR 0.60, 95% CI: 0.42, 0.86] and intra-cranial bleeding [HR 0.54, 95% CI: 0.36, 0.81] was much lower in those that received DOAC compared to warfarin. Compared to those receiving warfarin, those on DOACs had substantially reduced risk of any clinical thromboembolic events [HR 0.52, 95% CI: 0.39, 0.70]. No significant differences were noted for all-cause mortality [HR 0.88, 95% CI: 0.74, 1.05], cardiovascular events/myocardial infarction (MI) [HR 0.58, 95% CI: 0.33, 1.04] and and readmission rates [HR 0.85, 95% CI: 0.62, 1.18].
CONCLUSIONS
Findings suggest that the use DOACs in patients with AF with bioprosthetic valve replacement or repair is comparatively better than vitamin K antagonists in reducing the risk of bleeding and thrombo-embolic events. Future studies with a randomized design and larger sample sizes are needed to further substantiate these findings.
Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Factor Xa Inhibitors; Heart Valves; Humans; Vitamin K
PubMed: 34355372
DOI: 10.26355/eurrev_202108_26457 -
BMJ Open Jun 2015To investigate the clinical and cost-effectiveness of self-monitoring of coagulation status in people receiving long-term vitamin K antagonist therapy compared with... (Review)
Review
OBJECTIVES
To investigate the clinical and cost-effectiveness of self-monitoring of coagulation status in people receiving long-term vitamin K antagonist therapy compared with standard clinic care.
DESIGN
Systematic review of current evidence and economic modelling.
DATA SOURCES
Major electronic databases were searched up to May 2013. The economic model parameters were derived from the clinical effectiveness review, routine sources of cost data and advice from clinical experts.
STUDY ELIGIBILITY CRITERIA
Randomised controlled trials (RCTs) comparing self-monitoring versus standard clinical care in people with different clinical conditions. Self-monitoring included both self-management (patients conducted the tests and adjusted their treatment according to an algorithm) and self-testing (patients conducted the tests, but received treatment recommendations from a clinician). Various point-of-care coagulometers were considered.
RESULTS
26 RCTs (8763 participants) were included. Both self-management and self-testing were as safe as standard care in terms of major bleeding events (RR 1.08, 95% CI 0.81 to 1.45, p=0.690, and RR 0.99, 95% CI 0.80 to 1.23, p=0.92, respectively). Self-management was associated with fewer thromboembolic events (RR 0.51, 95% CI 0.37 to 0.69, p ≤ 0.001) and with a borderline significant reduction in all-cause mortality (RR 0.68, 95% CI 0.46 to 1.01, p=0.06) than standard care. Self-testing resulted in a modest increase in time in therapeutic range compared with standard care (weighted mean difference, WMD 4.4%, 95% CI 1.71 to 7.18, p=0.02). Total health and social care costs over 10 years were £7324 with standard care and £7326 with self-monitoring (estimated quality adjusted life year, QALY gain was 0.028). Self-monitoring was found to have ∼ 80% probability of being cost-effective compared with standard care applying a ceiling willingness-to-pay threshold of £20,000 per QALY gained. Within the base case model, applying the pooled relative effect of thromboembolic events, self-management alone was highly cost-effective while self-testing was not.
CONCLUSIONS
Self-monitoring appears to be a safe and cost-effective option.
TRIAL REGISTRATION NUMBER
PROSPERO CRD42013004944.
Topics: Anticoagulants; Cost-Benefit Analysis; Hemorrhage; Humans; Self Care; Thromboembolism; Vitamin K
PubMed: 26112222
DOI: 10.1136/bmjopen-2015-007758 -
European Journal of Vascular and... May 2019The aim was to review the relative efficacy and safety of anticoagulation for managing venous thromboembolism (VTE) in patients with cancer. (Meta-Analysis)
Meta-Analysis
OBJECTIVE/BACKGROUND
The aim was to review the relative efficacy and safety of anticoagulation for managing venous thromboembolism (VTE) in patients with cancer.
METHODS
A systematic review and meta-analysis was carried out. On 17 May 2018 the MEDLINE and Scopus databases were searched for randomised controlled trials (RCTs). Eligible RCTs had to be performed in patients with cancer exclusively or to report results on a subset of patients with cancer. The main study outcomes (efficacy/recurrent VTE and safety/bleeding events) were expressed as risk ratios (RR) with a 95% confidence interval (CI). The quality of evidence was assessed following the GRADE method.
RESULTS
Twenty-three RCTs with 6980 patients were identified. Low molecular weight heparins (LMWHs) were more effective than vitamin K antagonists (VKAs) in preventing recurrent VTE (RR 0.58, 95% CI 0.45-0.75) and deep vein thrombosis (RR 0.44, 95% CI 0.29-0.69) but not pulmonary embolism (PE), bleeding, or overall mortality. Direct oral anticoagulants (DOACs) were more effective than VKAs in preventing recurrent VTE (RR 0.65, 95% CI 0.45-0.95) but not DVT, PE, overall mortality, or bleeding. However, anti-Xa DOACs were more effective (RR for VTE 0.64, 95% CI 0.42-0.97) and caused less bleeding than VKAs, although major bleeding was reduced only with DOACs not requiring initial parenteral anticoagulation (RR 0.45, 95% CI 0.21-0.97). In a direct comparison, DOACs were more effective than LMWHs in preventing VTE recurrence (RR 0.64, 95% CI 0.45-0.90) but caused more major bleeding (RR 1.75, 95% CI 1.10-2.77), with no difference in fatal bleeding and overall mortality. Quality of evidence, where sufficient, was mostly moderate or high.
CONCLUSION
Compared with VKAs, LMWHs and DOACs are more effective in treating VTE, but the former caused less bleeding. DOACs are more effective than LMWHs in preventing VTE recurrence but may carry a higher risk of major bleeding, pending additional information by ongoing trials.
Topics: Anticoagulants; Fondaparinux; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Oligosaccharides; Pulmonary Embolism; Secondary Prevention; Venous Thromboembolism; Venous Thrombosis; Vitamin K
PubMed: 31097186
DOI: 10.1016/j.ejvs.2018.11.004