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Chest May 2023The management of patients who are receiving chronic oral anticoagulation therapy and require an elective surgery or an invasive procedure is a common clinical scenario. (Meta-Analysis)
Meta-Analysis
BACKGROUND
The management of patients who are receiving chronic oral anticoagulation therapy and require an elective surgery or an invasive procedure is a common clinical scenario.
RESEARCH QUESTION
What is the best available evidence to support the development of American College of Chest Physicians guidelines on the perioperative management of patients who are receiving long-term vitamin K agonist (VKA) or direct oral anticoagulant (DOAC) and require elective surgery or procedures?
STUDY DESIGN AND METHODS
A literature search including multiple databases from database inception through July 16, 2020, was performed. Meta-analyses were conducted when appropriate.
RESULTS
In patients receiving VKA (warfarin) undergoing elective noncardiac surgery, shorter (< 3 days) VKA interruption is associated with an increased risk of major bleeding. In patients who required VKA interruption, heparin bridging (mostly with low-molecular-weight heparin [LMWH]) was associated with a statistically significant increased risk of major bleed, representing a very low certainty of evidence (COE). Compared with DOAC interruption 1 to 4 days before surgery, continuing DOACs may be associated with higher risk of bleeding demonstrated in some, but not all studies. In patients who needed DOAC interruption, bridging with LMWH may be associated with a statistically significant increased risk of bleeding, representing a low COE.
INTERPRETATION
The certainty in the evidence supporting the perioperative management of anticoagulants remains limited. No high-quality evidence exists to support the practice of heparin bridging during the interruption of VKA or DOAC therapy for an elective surgery or procedure, or for the practice of interrupting VKA therapy for minor procedures, including cardiac device implantation, or continuation of a DOAC vs short-term interruption of a DOAC in the perioperative period.
Topics: Humans; Heparin, Low-Molecular-Weight; Anticoagulants; Heparin; Warfarin; Fibrinolytic Agents; Hemorrhage; Vitamin K; Administration, Oral
PubMed: 36462533
DOI: 10.1016/j.chest.2022.11.032 -
BMJ (Clinical Research Ed.) Mar 2022To systematically compare the effect of direct oral anticoagulants and low molecular weight heparin for thromboprophylaxis on the benefits and harms to patients... (Meta-Analysis)
Meta-Analysis
Benefits and harms of direct oral anticoagulation and low molecular weight heparin for thromboprophylaxis in patients undergoing non-cardiac surgery: systematic review and network meta-analysis of randomised trials.
OBJECTIVE
To systematically compare the effect of direct oral anticoagulants and low molecular weight heparin for thromboprophylaxis on the benefits and harms to patients undergoing non-cardiac surgery.
DESIGN
Systematic review and network meta-analysis of randomised controlled trials.
DATA SOURCES
Medline, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL), up to August 2021.
REVIEW METHODS
Randomised controlled trials in adults undergoing non-cardiac surgery were selected, comparing low molecular weight heparin (prophylactic (low) or higher dose) with direct oral anticoagulants or with no active treatment. Main outcomes were symptomatic venous thromboembolism, symptomatic pulmonary embolism, and major bleeding. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used for network meta-analyses. Abstracts and full texts were screened independently in duplicate. Data were abstracted on study participants, interventions, and outcomes, and risk of bias was assessed independently in duplicate. Frequentist network meta-analysis with multivariate random effects models provided odds ratios with 95% confidence intervals, and GRADE (grading of recommendations, assessment, development, and evaluation) assessments indicated the certainty of the evidence.
RESULTS
68 randomised controlled trials were included (51 orthopaedic, 10 general, four gynaecological, two thoracic, and one urological surgery), involving 45 445 patients. Low dose (odds ratio 0.33, 95% confidence interval 0.16 to 0.67) and high dose (0.19, 0.07 to 0.54) low molecular weight heparin, and direct oral anticoagulants (0.17, 0.07 to 0.41) reduced symptomatic venous thromboembolism compared with no active treatment, with absolute risk differences of 1-100 per 1000 patients, depending on baseline risks (certainty of evidence, moderate to high). None of the active agents reduced symptomatic pulmonary embolism (certainty of evidence, low to moderate). Direct oral anticoagulants and low molecular weight heparin were associated with a 2-3-fold increase in the odds of major bleeding compared with no active treatment (certainty of evidence, moderate to high), with absolute risk differences as high as 50 per 1000 in patients at high risk. Compared with low dose low molecular weight heparin, high dose low molecular weight heparin did not reduce symptomatic venous thromboembolism (0.57, 0.26 to 1.27) but increased major bleeding (1.87, 1.06 to 3.31); direct oral anticoagulants reduced symptomatic venous thromboembolism (0.53, 0.32 to 0.89) and did not increase major bleeding (1.23, 0.89 to 1.69).
CONCLUSIONS
Direct oral anticoagulants and low molecular weight heparin reduced venous thromboembolism compared with no active treatment but probably increased major bleeding to a similar extent. Direct oral anticoagulants probably prevent symptomatic venous thromboembolism to a greater extent than prophylactic low molecular weight heparin.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42018106181.
Topics: Anticoagulants; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Network Meta-Analysis; Postoperative Complications; Pulmonary Embolism; Randomized Controlled Trials as Topic; Surgical Procedures, Operative; Treatment Outcome; Venous Thromboembolism
PubMed: 35264372
DOI: 10.1136/bmj-2021-066785 -
Stroke Oct 2022High level evidence for direct oral anticoagulants (DOACs) in patients with cerebral venous thrombosis is lacking. We performed a systematic review and meta-analysis to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
High level evidence for direct oral anticoagulants (DOACs) in patients with cerebral venous thrombosis is lacking. We performed a systematic review and meta-analysis to assess the efficacy and safety of DOACs versus vitamin K antagonists in patients with cerebral venous thrombosis.
METHODS
This systematic review was registered in PROSPERO (CRD42021228800). We searched MEDLINE (via Ovid), EMBASE, CINAHL, and the Web of Science Core Collection between January 1, 2007 and Feb 22, 2022. Search terms included a combination of keywords and controlled vocabulary terms for cerebral venous thrombosis, vitamin K antagonists/warfarin, and DOACs. We included both randomized and nonrandomized studies that compared vitamin K antagonists and DOACs in 5 or more patients with cerebral venous thrombosis. Where studies were sufficiently similar, we performed meta-analyses for efficacy (recurrent venous thromboembolism and complete recanalization) and safety (major hemorrhage) outcomes, using relative risks (RRs).
RESULTS
Out of 10 665 records identified, we screened 254 as potentially eligible. Nineteen studies (16 observational studies [n=1735] and 3 randomized controlled trials [n=215]) met the inclusion criteria. All 3 randomized controlled trials had some concerns, and all 16 observational studies had at least moderate risk of bias. When compared with vitamin K antagonist treatment, DOAC had comparable risks of recurrent venous thromboembolism (relative risk [RR], 0.85 [95% CI, 0.52-1.37], I=0%), major hemorrhage (RR, 0.70 [95% CI, 0.40-1.21], I=0%), intracranial hemorrhage (RR, 0.58 [95% CI, 0.30-1.12]; I=0%), death (RR, 1.14 [95% CI, 0.54-2.43], I=1%), and complete venous recanalization (RR, 0.98 [95% CI, 0.87-1.11]; I=0%).
CONCLUSIONS
This systematic review and meta-analysis suggest that in patients with cerebral venous thrombosis, DOACs, and warfarin may have comparable efficacy and safety. Given the limitations of the studies included (low number of randomized controlled trials, modest total sample size, rare outcome events), our findings should be interpreted with caution pending confirmation by ongoing randomized controlled trials and large, prospective, observational studies.
Topics: Administration, Oral; Anticoagulants; Fibrinolytic Agents; Hemorrhage; Humans; Intracranial Thrombosis; Prospective Studies; Venous Thromboembolism; Venous Thrombosis; Vitamin K; Warfarin
PubMed: 35938419
DOI: 10.1161/STROKEAHA.122.039579 -
American Journal of Hematology Jul 2021The effectiveness and safety of non-heparin anticoagulants for the treatment of heparin-induced thrombocytopenia (HIT) are not fully established, and the optimal... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
The effectiveness and safety of non-heparin anticoagulants for the treatment of heparin-induced thrombocytopenia (HIT) are not fully established, and the optimal treatment strategy is unknown. In a systematic review and meta-analysis, we aimed to determine precise rates of platelet recovery, new or progressive thromboembolism (TE), major bleeding, and death for all non-heparin anticoagulants and to study potential sources of variability.
METHODS
Following a detailed protocol (PROSPERO: CRD42020219027), EMBASE and Medline were searched for all studies reporting clinical outcomes of patients treated with non-heparin anticoagulants (argatroban, danaparoid, fondaparinux, direct oral anticoagulants [DOAC], bivalirudin, and other hirudins) for acute HIT. Proportions of patients with the outcomes of interest were pooled using a random-effects model for each drug. The influence of the patient population, the diagnostic test used, the study design, and the type of article was assessed.
RESULTS
Out of 3194 articles screened, 92 studies with 119 treatment groups describing 4698 patients were included. The pooled rates of platelet recovery ranged from 74% (bivalirudin) to 99% (fondaparinux), TE from 1% (fondaparinux) to 7% (danaparoid), major bleeding from 1% (DOAC) to 14% (bivalirudin), and death from 7% (fondaparinux) to 19% (bivalirudin). Confidence intervals were mostly overlapping, and results were not influenced by patient population, diagnostic test used, study design, or type of article.
DISCUSSION
Effectiveness and safety outcomes were similar among various anticoagulants, and significant factors affecting these outcomes were not identified. These findings support fondaparinux and DOACs as viable alternatives to conventional anticoagulants for treatment of acute HIT in clinical practice.
Topics: Anticoagulants; Blood Platelets; Hemorrhage; Heparin; Humans; Thrombocytopenia; Thromboembolism; Treatment Outcome
PubMed: 33857342
DOI: 10.1002/ajh.26194 -
The Cochrane Database of Systematic... Jan 2022Upper gastrointestinal (GI) bleeding is a common reason for emergency hospital admission. Proton pump inhibitors (PPIs) reduce gastric acid production and are used to... (Review)
Review
BACKGROUND
Upper gastrointestinal (GI) bleeding is a common reason for emergency hospital admission. Proton pump inhibitors (PPIs) reduce gastric acid production and are used to manage upper GI bleeding. However, there is conflicting evidence regarding the clinical efficacy of proton pump inhibitors initiated before endoscopy in people with upper gastrointestinal bleeding.
OBJECTIVES
To assess the effects of PPI treatment initiated prior to endoscopy in people with acute upper GI bleeding.
SEARCH METHODS
We searched the CENTRAL, MEDLINE, Embase and CINAHL databases and major conference proceedings to October 2008, for the previous versions of this review, and in April 2018, October 2019, and 3 June 2021 for this update. We also contacted experts in the field and searched trial registries and references of trials for any additional trials.
SELECTION CRITERIA
We selected randomised controlled trials (RCTs) that compared treatment with a PPI (oral or intravenous) versus control treatment with either placebo, histamine-2 receptor antagonist (HRA) or no treatment, prior to endoscopy in hospitalised people with uninvestigated upper GI bleeding.
DATA COLLECTION AND ANALYSIS
At least two review authors independently assessed study eligibility, extracted study data and assessed risk of bias. Outcomes assessed at 30 days were: mortality (our primary outcome), rebleeding, surgery, high-risk stigmata of recent haemorrhage (active bleeding, non-bleeding visible vessel or adherent clot) at index endoscopy, endoscopic haemostatic treatment at index endoscopy, time to discharge, blood transfusion requirements and adverse effects. We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
We included six RCTs comprising 2223 participants. No new studies have been published after the literature search performed in 2008 for the previous version of this review. Of the included studies, we considered one to be at low risk of bias, two to be at unclear risk of bias, and three at high risk of bias. Our meta-analyses suggest that pre-endoscopic PPI use may not reduce mortality (OR 1.14, 95% CI 0.76 to 1.70; 5 studies; low-certainty evidence), and may reduce rebleeding (OR 0.81, 95% CI 0.62 to 1.06; 5 studies; low-certainty evidence). In addition, pre-endoscopic PPI use may not reduce the need for surgery (OR 0.91, 95% CI 0.65 to 1.26; 6 studies; low-certainty evidence), and may not reduce the proportion of participants with high-risk stigmata of recent haemorrhage at index endoscopy (OR 0.80, 95% CI 0.52 to 1.21; 4 studies; low-certainty evidence). Pre-endoscopic PPI use likely reduces the need for endoscopic haemostatic treatment at index endoscopy (OR 0.68, 95% CI 0.50 to 0.93; 3 studies; moderate-certainty evidence). There were insufficient data to determine the effect of pre-endoscopic PPI use on blood transfusions (2 studies; meta-analysis not possible; very low-certainty evidence) and time to discharge (1 study; very low-certainty evidence). There was no substantial heterogeneity amongst trials in any analysis.
AUTHORS' CONCLUSIONS
There is moderate-certainty evidence that PPI treatment initiated before endoscopy for upper GI bleeding likely reduces the requirement for endoscopic haemostatic treatment at index endoscopy. However, there is insufficient evidence to conclude whether pre-endoscopic PPI treatment increases, reduces or has no effect on other clinical outcomes, including mortality, rebleeding and need for surgery. Further well-designed RCTs that conform to current standards for endoscopic haemostatic treatment and appropriate co-interventions, and that ensure high-dose PPIs are only given to people who received endoscopic haemostatic treatment, regardless of initial randomisation, are warranted. However, as it may be unrealistic to achieve the optimal information size, pragmatic multicentre trials may provide valuable evidence on this topic.
Topics: Acute Disease; Endoscopy; Gastrointestinal Hemorrhage; Histamine H2 Antagonists; Humans; Proton Pump Inhibitors
PubMed: 34995368
DOI: 10.1002/14651858.CD005415.pub4 -
Stroke Jun 2022Aneurysmal subarachnoid hemorrhage (aSAH) is associated with high mortality and morbidity. We aimed to determine the relative benefits of pharmacological prophylactic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Aneurysmal subarachnoid hemorrhage (aSAH) is associated with high mortality and morbidity. We aimed to determine the relative benefits of pharmacological prophylactic treatments in patients with aneurysmal subarachnoid hemorrhage by performing a network meta-analysis of randomized trials.
METHODS
We searched Medline, Web of Science, Embase, Scopus, ProQuest, and Cochrane Central to February 2020. Pairs of reviewers independently identified eligible trials, extracted data, and assessed the risk of bias. Eligible trials compared the prophylactic effects of any oral or intravenous medications or intracranial drug-eluting implants to one another or placebo or standard of care in adult hospitalized patients with confirmed aneurysmal subarachnoid hemorrhage. We used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to assess the certainty of the evidence.
RESULTS
We included 53 trials enrolling 10 415 patients. Nimodipine likely reduces all-cause mortality compared to placebo (odds ratio [OR],0.73 [95% CI, 0.53-1.00]; moderate certainty; absolute risk reduction (ARR), -3.35%). Nimodipine (OR, 1.46 [95% CI, 1.07-1.99]; high certainty; absolute risk increase, 8.25%) and cilostazol (OR, 3.73 [95% CI, 1.14-12.18]; moderate certainty; absolute risk increase, 23.15%) were the most effective treatments in improving disability at the longest follow-up. Compared to placebo, clazosentan (10 mg/kg; OR, 0.39 [95% CI, 0.22-0.68]; high certainty; ARR, -16.65%), nicardipine (OR, 0.48 [95% CI, 0.24-0.94]; moderate certainty; ARR, -13.70%), fasudil (OR, 0.55 [95% CI, 0.31-0.98]; moderate certainty; ARR, -11.54%), and magnesium (OR, 0.66 [95% CI, 0.46-0.94]; high certainty; ARR, -8.37%) proved most effective in reducing the likelihood of delayed cerebral ischemia.
CONCLUSIONS
Nimodipine and cilostazol are likely the most effective treatments in preventing morbidity and mortality in patients with aneurysmal subarachnoid hemorrhage. Clazosentan, nicardipine, fasudil, and magnesium showed beneficial effects on delayed cerebral ischemia and vasospasm but they were not found to reduce mortality or disability. Future trials are warranted to elaborately investigate the prophylactic effects of medications that may improve mortality and long-term functional outcomes, such as cilostazol and clazosentan.
REGISTRATION
URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42019122183.
Topics: Adult; Brain Ischemia; Cilostazol; Humans; Magnesium; Morbidity; Network Meta-Analysis; Nicardipine; Nimodipine; Randomized Controlled Trials as Topic; Subarachnoid Hemorrhage; Vasospasm, Intracranial
PubMed: 35354302
DOI: 10.1161/STROKEAHA.121.035699 -
Clinical Drug Investigation Apr 2021BACKGROUND AND OBJECTIVE: Systematic reviews and meta-analyses of direct oral anticoagulants (DOACs) for patients with chronic kidney disease (CKD) or dialysis patients... (Comparative Study)
Comparative Study Meta-Analysis
UNLABELLED
BACKGROUND AND OBJECTIVE: Systematic reviews and meta-analyses of direct oral anticoagulants (DOACs) for patients with chronic kidney disease (CKD) or dialysis patients are lacking. We aimed to compare the efficacy and safety of DOACs and warfarin in patients with CKD requiring anticoagulation therapy.
METHODS
We performed a systematic review and meta-analysis of six randomized controlled trials and 19 observational studies, with the inclusion criteria being a comparative study between DOACs and warfarin in patients with CKD or dialysis patients from database inception until August 2020. The efficacy outcomes were stroke, systemic embolism (SE), or venous thromboembolism (VTE), and the safety outcome was major bleeding.
RESULTS
Compared with warfarin, DOACs significantly reduced the risk of stroke/SE/VTE by 22% (hazard ratio [HR] = 0.78, 95% confidence interval [CI] 0.64-0.95) and major bleeding by 17% (HR = 0.83, 95% CI 0.71-0.97). On comparing factor Xa inhibitors and dabigatran with warfarin separately, factor Xa inhibitors significantly reduced the risk of stroke/SE/VTE (HR = 0.78, 95% CI 0.62-0.98) and major bleeding (HR = 0.76, 95% CI 0.64-0.91) overall in patients. Comparing each DOACs with warfarin separately, apixaban was associated with a significantly better risk reduction of stroke/SE/VTE (25% risk reduction) and major bleeding (35% risk reduction) than warfarin. Compared with warfarin, DOACs significantly reduced the risk of stroke, SE, or VTE by 19% (HR = 0.81, 95% CI 0.68-0.97) in patients with CKD stage 3 and significantly lowered the risk of major bleeding by 31% (HR = 0.69, 95% CI 0.56-0.85) in patients with CKD stages 4-5.
CONCLUSIONS
In pooled, analyzed randomized controlled trials and observational studies, DOACs were associated with better efficacy in early CKD, as well as similar efficacy and safety outcomes to warfarin in patients with CKD stages 4-5 or dialysis patients. The results of patients with CKD stages 4-5 and dialysis patients were from observational studies. Well-designed randomized controlled trials focused on DOAC use in patients with CKD and dialysis patients are needed. PROSPERO register number: CRD42020150599, 6 February, 2020.
Topics: Anticoagulants; Atrial Fibrillation; Dabigatran; Factor Xa Inhibitors; Hemorrhage; Humans; Randomized Controlled Trials as Topic; Renal Dialysis; Renal Insufficiency, Chronic; Stroke; Venous Thromboembolism; Warfarin
PubMed: 33709339
DOI: 10.1007/s40261-021-01016-7 -
Journal of Thrombosis and Haemostasis :... Oct 2023Direct oral anticoagulants (DOACs) represent a cornerstone of adult venous thromboembolism (VTE) treatment. Recently, randomized controlled trials (RCTs) investigating... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Direct oral anticoagulants (DOACs) represent a cornerstone of adult venous thromboembolism (VTE) treatment. Recently, randomized controlled trials (RCTs) investigating DOACs in pediatrics have been performed.
OBJECTIVES
To evaluate the efficacy and safety of DOACs in the pediatric population.
METHODS
We systematically searched MEDLINE (PubMed), EMBASE, and ClinicalTrials.gov from initiation up to August 20, 2022, for RCTs comparing DOACs to standard of care (SOC) in patients aged <18 years according to PRISMA guidelines (PROSPERO registration CRD42022353870). The primary analysis was performed according to the anticoagulation intensity and clinical setting (ie, prophylaxis in cardiac disease or treatment in VTE). Efficacy outcomes were all-cause mortality and VTE. Safety outcomes were major bleeding (MB), clinically relevant non-MB, any bleeding, serious adverse events, and discontinuation due to adverse events (AEs).
RESULTS
Seven RCTs were included in the systematic review and 6 in the meta-analysis (3 prophylaxis in cardiac disease and 3 treatment in VTE). DOACs showed a significant reduction of VTE recurrence for treatment (odds ratio [OR] = 0.42; 95% CI, 0.19-0.94) and a nonsignificant reduction in VTE occurrence in prophylaxis (OR = 0.22; 95% CI, 0.03-1.55). No differences were observed for any bleeding, serious AEs, and MB in prophylaxis. Nonsignificant trends were observed for clinically relevant non-MB, MB in treatment, and discontinuation due to AE in prophylaxis. We found a significant increase in discontinuation due to AE in treatment.
CONCLUSIONS
DOAC treatment seems to reduce VTE compared with SOC without major safety issues in the pediatric population, whereas DOAC prophylaxis seems at least comparable to SOC.
Topics: Humans; Child; Anticoagulants; Venous Thromboembolism; Hemorrhage; Blood Coagulation; Heart Diseases; Administration, Oral
PubMed: 37481075
DOI: 10.1016/j.jtha.2023.07.011 -
The American Journal of Medicine Oct 2022The role of antisecretory drugs for the prevention of upper gastrointestinal bleeding in patients using anticoagulants is unclear. We investigated this question in a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The role of antisecretory drugs for the prevention of upper gastrointestinal bleeding in patients using anticoagulants is unclear. We investigated this question in a systematic review and meta-analysis.
METHODS
We searched Embase, PubMed, Web of Science, Scopus, the Cochrane Library, and clinicaltrials.gov thru April 2021 for controlled randomized trials and observational studies evaluating the association of proton pump inhibitors (PPIs) or H2-receptor antagonists with overt upper gastrointestinal bleeding in patients using anticoagulants. Independent duplicate review, data extraction, and risk of bias assessment were performed. Observational studies were included only if they provided results controlled for at least 2 variables. Meta-analyses were performed using random effects models.
RESULTS
Six observational studies and 1 randomized trial were included. All but 1 study had low risk of bias. None of the studies excluded patients with concomitant aspirin or nonsteroidal anti-inflammatory drug use. For PPIs, the pooled relative risk of upper gastrointestinal bleeding was 0.67 (95% confidence interval 0.61, 0.74) with low statistical heterogeneity (I = 15%). Individual studies showed greater treatment effect in patients with higher risk for upper gastrointestinal bleeding (eg, nonsteroidal anti-inflammatory drug or aspirin use, elevated bleeding risk score). A single observational study evaluating the association of H2-receptor antagonists with upper gastrointestinal bleeding found a relative risk of 0.69 (95% confidence interval 0.24-2.02).
CONCLUSIONS
Evidence drawn mostly from observational studies with low risk of bias demonstrate that PPIs reduce upper gastrointestinal bleeding in patients prescribed oral anticoagulants. The benefit appears to be most clearcut and substantial in patients with elevated risk of upper gastrointestinal bleeding.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Aspirin; Gastrointestinal Agents; Gastrointestinal Hemorrhage; Histamine H2 Antagonists; Humans; Observational Studies as Topic; Proton Pump Inhibitors
PubMed: 35679879
DOI: 10.1016/j.amjmed.2022.05.031 -
BMJ (Clinical Research Ed.) Jul 2022To assess the benefits and harms of different types and doses of anticoagulant drugs for the prevention of venous thromboembolism in patients who are acutely ill and... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To assess the benefits and harms of different types and doses of anticoagulant drugs for the prevention of venous thromboembolism in patients who are acutely ill and admitted to hospital.
DESIGN
Systematic review and network meta-analysis.
DATA SOURCES
Cochrane CENTRAL, PubMed/Medline, Embase, Web of Science, clinical trial registries, and national health authority databases. The search was last updated on 16 November 2021.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Published and unpublished randomised controlled trials that evaluated low or intermediate dose low-molecular-weight heparin, low or intermediate dose unfractionated heparin, direct oral anticoagulants, pentasaccharides, placebo, or no intervention for the prevention of venous thromboembolism in acutely ill adult patients in hospital.
MAIN OUTCOME MEASURES
Random effects, bayesian network meta-analyses used four co-primary outcomes: all cause mortality, symptomatic venous thromboembolism, major bleeding, and serious adverse events at or closest timing to 90 days. Risk of bias was also assessed using the Cochrane risk-of-bias 2.0 tool. The quality of evidence was graded using the Confidence in Network Meta-Analysis framework.
RESULTS
44 randomised controlled trials that randomly assigned 90 095 participants were included in the main analysis. Evidence of low to moderate quality suggested none of the interventions reduced all cause mortality compared with placebo. Pentasaccharides (odds ratio 0.32, 95% credible interval 0.08 to 1.07), intermediate dose low-molecular-weight heparin (0.66, 0.46 to 0.93), direct oral anticoagulants (0.68, 0.33 to 1.34), and intermediate dose unfractionated heparin (0.71, 0.43 to 1.19) were most likely to reduce symptomatic venous thromboembolism (very low to low quality evidence). Intermediate dose unfractionated heparin (2.63, 1.00 to 6.21) and direct oral anticoagulants (2.31, 0.82 to 6.47) were most likely to increase major bleeding (low to moderate quality evidence). No conclusive differences were noted between interventions regarding serious adverse events (very low to low quality evidence). When compared with no intervention instead of placebo, all active interventions did more favourably with regard to risk of venous thromboembolism and mortality, and less favourably with regard to risk of major bleeding. The results were robust in prespecified sensitivity and subgroup analyses.
CONCLUSIONS
Low-molecular-weight heparin in an intermediate dose appears to confer the best balance of benefits and harms for prevention of venous thromboembolism. Unfractionated heparin, in particular the intermediate dose, and direct oral anticoagulants had the least favourable profile. A systematic discrepancy was noted in intervention effects that depended on whether placebo or no intervention was the reference treatment. Main limitations of this study include the quality of the evidence, which was generally low to moderate due to imprecision and within-study bias, and statistical inconsistency, which was addressed post hoc.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42020173088.
Topics: Anticoagulants; Bayes Theorem; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Hospitals; Humans; Network Meta-Analysis; Randomized Controlled Trials as Topic; Thrombosis; Venous Thromboembolism
PubMed: 35788047
DOI: 10.1136/bmj-2022-070022