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Immunity, Inflammation and Disease Mar 2023Since publishing successful clinical trial results of mRNA coronavirus disease 2019 (COVID-19) vaccines in December 2020, multiple reports have arisen about... (Review)
Review
BACKGROUND AND OBJECTIVES
Since publishing successful clinical trial results of mRNA coronavirus disease 2019 (COVID-19) vaccines in December 2020, multiple reports have arisen about cardiovascular complications following the mRNA vaccination. This study provides an in-depth account of various cardiovascular adverse events reported after the mRNA vaccines' first or second dose including pericarditis/myopericarditis, myocarditis, hypotension, hypertension, arrhythmia, cardiogenic shock, stroke, myocardial infarction/STEMI, intracranial hemorrhage, thrombosis (deep vein thrombosis, cerebral venous thrombosis, arterial or venous thrombotic events, portal vein thrombosis, coronary thrombosis, microvascular small bowel thrombosis), and pulmonary embolism.
METHODS
A systematic review of original studies reporting confirmed cardiovascular manifestations post-mRNA COVID-19 vaccination was performed. Following the PRISMA guidelines, electronic databases (PubMed, PMC NCBI, and Cochrane Library) were searched until January 2022. Baseline characteristics of patients and disease outcomes were extracted from relevant studies.
RESULTS
A total of 81 articles analyzed confirmed cardiovascular complications post-COVID-19 mRNA vaccines in 17,636 individuals and reported 284 deaths with any mRNA vaccine. Of 17,636 cardiovascular events with any mRNA vaccine, 17,192 were observed with the BNT162b2 (Pfizer-BioNTech) vaccine, 444 events with mRNA-1273 (Moderna). Thrombosis was frequently reported with any mRNA vaccine (n = 13,936), followed by stroke (n = 758), myocarditis (n = 511), myocardial infarction (n = 377), pulmonary embolism (n = 301), and arrhythmia (n = 254). Stratifying the results by vaccine type showed that thrombosis (80.8%) was common in the BNT162b2 cohort, while stroke (39.9%) was common with mRNA-1273 for any dose. The time between the vaccination dosage and the first symptom onset averaged 5.6 and 4.8 days with the mRNA-1273 vaccine and BNT162b2, respectively. The mRNA-1273 cohort reported 56 deaths compared to the 228 with BNT162b2, while the rest were discharged or transferred to the ICU.
CONCLUSION
Available literature includes more studies with the BNT162b2 vaccine than mRNA-1273. Future studies must report mortality and adverse cardiovascular events by vaccine types.
Topics: Humans; 2019-nCoV Vaccine mRNA-1273; BNT162 Vaccine; COVID-19; COVID-19 Vaccines; Myocardial Infarction; Myocarditis; Pulmonary Embolism; Stroke; Thrombocytopenia; Thrombosis
PubMed: 36988252
DOI: 10.1002/iid3.807 -
Pediatric Critical Care Medicine : a... Jan 2022Critically ill children frequently receive plasma and platelet transfusions. We sought to determine evidence-based recommendations, and when evidence was insufficient,...
Executive Summary of Recommendations and Expert Consensus for Plasma and Platelet Transfusion Practice in Critically Ill Children: From the Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding (TAXI-CAB).
OBJECTIVES
Critically ill children frequently receive plasma and platelet transfusions. We sought to determine evidence-based recommendations, and when evidence was insufficient, we developed expert-based consensus statements about decision-making for plasma and platelet transfusions in critically ill pediatric patients.
DESIGN
Systematic review and consensus conference series involving multidisciplinary international experts in hemostasis, and plasma/platelet transfusion in critically ill infants and children (Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding [TAXI-CAB]).
SETTING
Not applicable.
PATIENTS
Children admitted to a PICU at risk of bleeding and receipt of plasma and/or platelet transfusions.
INTERVENTIONS
None.
MEASUREMENTS AND MAIN RESULTS
A panel of 29 experts in methodology, transfusion, and implementation science from five countries and nine pediatric subspecialties completed a systematic review and participated in a virtual consensus conference series to develop recommendations. The search included MEDLINE, EMBASE, and Cochrane Library databases, from inception to December 2020, using a combination of subject heading terms and text words for concepts of plasma and platelet transfusion in critically ill children. Four graded recommendations and 49 consensus expert statements were developed using modified Research and Development/UCLA and Grading of Recommendations, Assessment, Development, and Evaluation methodology. We focused on eight subpopulations of critical illness (1, severe trauma, intracranial hemorrhage, or traumatic brain injury; 2, cardiopulmonary bypass surgery; 3, extracorporeal membrane oxygenation; 4, oncologic diagnosis or hematopoietic stem cell transplantation; 5, acute liver failure or liver transplantation; 6, noncardiac surgery; 7, invasive procedures outside the operating room; 8, sepsis and/or disseminated intravascular coagulation) as well as laboratory assays and selection/processing of plasma and platelet components. In total, we came to consensus on four recommendations, five good practice statements, and 44 consensus-based statements. These results were further developed into consensus-based clinical decision trees for plasma and platelet transfusion in critically ill pediatric patients.
CONCLUSIONS
The TAXI-CAB program provides expert-based consensus for pediatric intensivists for the administration of plasma and/or platelet transfusions in critically ill pediatric patients. There is a pressing need for primary research to provide more evidence to guide practitioners.
Topics: Anemia; Child; Critical Care; Critical Illness; Erythrocyte Transfusion; Evidence-Based Medicine; Humans; Infant; Platelet Transfusion
PubMed: 34989711
DOI: 10.1097/PCC.0000000000002851 -
The Cochrane Database of Systematic... Oct 2021Stroke is the third leading cause of early death worldwide. Most ischaemic strokes are caused by a blood clot blocking an artery in the brain. Patient outcomes might be... (Review)
Review
BACKGROUND
Stroke is the third leading cause of early death worldwide. Most ischaemic strokes are caused by a blood clot blocking an artery in the brain. Patient outcomes might be improved if they are offered anticoagulants that reduce their risk of developing new blood clots and do not increase the risk of bleeding. This is an update of a Cochrane Review first published in 1995, with updates in 2004, 2008, and 2015.
OBJECTIVES
To assess the effectiveness and safety of early anticoagulation (within the first 14 days of onset) for people with acute presumed or confirmed ischaemic stroke. Our hypotheses were that, compared with a policy of avoiding their use, early anticoagulation would be associated with: • reduced risk of death or dependence in activities of daily living a few months after stroke onset; • reduced risk of early recurrent ischaemic stroke; • increased risk of symptomatic intracranial and extracranial haemorrhage; and • reduced risk of deep vein thrombosis and pulmonary embolism.
SEARCH METHODS
We searched the Cochrane Stroke Group Trials Register (August 2021); the Cochrane Database of Systematic Reviews (CDSR); the Cochrane Central Register of Controlled Trials (CENTRAL; 2021, Issue 7), in the Cochrane Library (searched 5 August 2021); MEDLINE (2014 to 5 August 2021); and Embase (2014 to 5 August 2021). In addition, we searched ongoing trials registries and reference lists of relevant papers. For previous versions of this review, we searched the register of the Antithrombotic Trialists' (ATT) Collaboration, consulted MedStrategy (1995), and contacted relevant drug companies.
SELECTION CRITERIA
Randomised trials comparing early anticoagulant therapy (started within two weeks of stroke onset) with control in people with acute presumed or confirmed ischaemic stroke.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials for inclusion, assessed trial quality, and extracted data. We assessed the overall certainty of the evidence for each outcome using RoB1 and GRADE methods.
MAIN RESULTS
We included 28 trials involving 24,025 participants. Quality of the trials varied considerably. We considered some studies to be at unclear or high risk of selection, performance, detection, attrition, or reporting bias. Anticoagulants tested were standard unfractionated heparin, low-molecular-weight heparins, heparinoids, oral anticoagulants, and thrombin inhibitors. Over 90% of the evidence is related to effects of anticoagulant therapy initiated within the first 48 hours of onset. No evidence suggests that early anticoagulation reduced the odds of death or dependence at the end of follow-up (odds ratio (OR) 0.98, 95% confidence interval (CI) 0.92 to 1.03; 12 RCTs, 22,428 participants; high-certainty evidence). Similarly, we found no evidence suggesting that anticoagulant therapy started within the first 14 days of stroke onset reduced the odds of death from all causes (OR 0.99, 95% CI 0.90 to 1.09; 22 RCTs, 22,602 participants; low-certainty evidence) during the treatment period. Although early anticoagulant therapy was associated with fewer recurrent ischaemic strokes (OR 0.75, 95% CI 0.65 to 0.88; 12 RCTs, 21,665 participants; moderate-certainty evidence), it was also associated with an increase in symptomatic intracranial haemorrhage (OR 2.47; 95% CI 1.90 to 3.21; 20 RCTs, 23,221 participants; moderate-certainty evidence). Similarly, early anticoagulation reduced the frequency of symptomatic pulmonary emboli (OR 0.60, 95% CI 0.44 to 0.81; 14 RCTs, 22,544 participants; high-certainty evidence), but this benefit was offset by an increase in extracranial haemorrhage (OR 2.99, 95% CI 2.24 to 3.99; 18 RCTs, 22,255 participants; moderate-certainty evidence).
AUTHORS' CONCLUSIONS
Since the last version of this review, four new relevant studies have been published, and conclusions remain consistent. People who have early anticoagulant therapy after acute ischaemic stroke do not demonstrate any net short- or long-term benefit. Treatment with anticoagulants reduced recurrent stroke, deep vein thrombosis, and pulmonary embolism but increased bleeding risk. Data do not support the routine use of any of the currently available anticoagulants for acute ischaemic stroke.
Topics: Activities of Daily Living; Anticoagulants; Brain Ischemia; Heparin; Humans; Ischemic Stroke; Stroke; Systematic Reviews as Topic
PubMed: 34676532
DOI: 10.1002/14651858.CD000024.pub5 -
Radiology Feb 2021Background The association of pulmonary embolism (PE) with deep vein thrombosis (DVT) in patients with coronavirus disease 2019 (COVID-19) remains unclear, and the... (Meta-Analysis)
Meta-Analysis
Background The association of pulmonary embolism (PE) with deep vein thrombosis (DVT) in patients with coronavirus disease 2019 (COVID-19) remains unclear, and the diagnostic accuracy of D-dimer tests for PE is unknown. Purpose To conduct meta-analysis of the study-level incidence of PE and DVT and to evaluate the diagnostic accuracy of D-dimer tests for PE from multicenter individual patient data. Materials and Methods A systematic literature search identified studies evaluating the incidence of PE or DVT in patients with COVID-19 from January 1, 2020, to June 15, 2020. These outcomes were pooled using a random-effects model and were further evaluated using metaregression analysis. The diagnostic accuracy of D-dimer tests for PE was estimated on the basis of individual patient data using the summary receiver operating characteristic curve. Results Twenty-seven studies with 3342 patients with COVID-19 were included in the analysis. The pooled incidence rates of PE and DVT were 16.5% (95% CI: 11.6, 22.9; = 0.93) and 14.8% (95% CI: 8.5, 24.5; = 0.94), respectively. PE was more frequently found in patients who were admitted to the intensive care unit (ICU) (24.7% [95% CI: 18.6, 32.1] vs 10.5% [95% CI: 5.1, 20.2] in those not admitted to the ICU) and in studies with universal screening using CT pulmonary angiography. DVT was present in 42.4% of patients with PE. D-dimer tests had an area under the receiver operating characteristic curve of 0.737 for PE, and D-dimer levels of 500 and 1000 μg/L showed high sensitivity (96% and 91%, respectively) but low specificity (10% and 24%, respectively). Conclusion Pulmonary embolism (PE) and deep vein thrombosis (DVT) occurred in 16.5% and 14.8% of patients with coronavirus disease 2019 (COVID-19), respectively, and more than half of patients with PE lacked DVT. The cutoffs of D-dimer levels used to exclude PE in preexisting guidelines seem applicable to patients with COVID-19. © RSNA, 2020 See also the editorial by Woodard in this issue.
Topics: Humans; Computed Tomography Angiography; COVID-19; Fibrin Fibrinogen Degradation Products; Pulmonary Embolism; SARS-CoV-2; Venous Thrombosis; Multicenter Studies as Topic
PubMed: 33320063
DOI: 10.1148/radiol.2020203557 -
Respiration; International Review of... 2022Prolonged mechanical ventilation (PMV) and weaning failure are factors associated with prolonged hospital length of stay and increased morbidity and mortality. In...
INTRODUCTION
Prolonged mechanical ventilation (PMV) and weaning failure are factors associated with prolonged hospital length of stay and increased morbidity and mortality. In addition to the burden these places on patients and their families, it also imposes high costs on the public health system. The aim of this systematic review was to identify risk factors for PMV and weaning failure.
METHODS
The study was conducted according to PRISMA guidelines. After a comprehensive search of the COCHRANE Library, CINHAL, Web of Science, MEDLINE, and the LILACS Database a PubMed request was made on June 8, 2020. Studies that examined risk factors for PMV, defined as mechanical ventilation ≥96 h, weaning failure, and prolonged weaning in German and English were considered eligible; reviews, meta-analyses, and studies in very specific patient populations whose results are not necessarily applicable to the majority of ICU patients as well as pediatric studies were excluded from the analysis. This systematic review was registered in the PROSPERO register under the number CRD42021271038.
RESULTS
Of 532 articles identified, 23 studies with a total of 23,418 patients met the inclusion criteria. Fourteen studies investigated risk factors of PMV including prolonged weaning, 9 studies analyzed risk factors of weaning failure. The concrete definitions of these outcomes varied considerably between studies. For PMV, a variety of risk factors were identified, including comorbidities, site of intubation, various laboratory or blood gas parameters, ventilator settings, functional parameters, and critical care scoring systems. The risk of weaning failure was mainly related to age, previous home mechanical ventilation (HMV), cause of ventilation, and preexisting underlying diseases. Elevated PaCO2 values during spontaneous breathing trials were indicative of prolonged weaning and weaning failure.
CONCLUSION
A direct comparison of risk factors was not possible because of the heterogeneity of the studies. The large number of different definitions and relevant parameters reflects the heterogeneity of patients undergoing PMV and those discharged to HMV after unsuccessful weaning. Multidimensional scores are more likely to reflect the full spectrum of patients ventilated in different ICUs than single risk factors.
Topics: Child; Critical Care; Humans; Intensive Care Units; Respiration, Artificial; Time Factors; Ventilator Weaning
PubMed: 35977525
DOI: 10.1159/000525604 -
JAMA Internal Medicine Mar 2020Patients undergoing total hip replacement (THR) and total knee replacement (TKR) receive venous thromboembolism (VTE) pharmacoprophylaxis. It is unclear which... (Meta-Analysis)
Meta-Analysis
Clinical Effectiveness and Safety of Aspirin for Venous Thromboembolism Prophylaxis After Total Hip and Knee Replacement: A Systematic Review and Meta-analysis of Randomized Clinical Trials.
IMPORTANCE
Patients undergoing total hip replacement (THR) and total knee replacement (TKR) receive venous thromboembolism (VTE) pharmacoprophylaxis. It is unclear which anticoagulant is preferable. Observational data suggest aspirin provides effective VTE prophylaxis.
OBJECTIVE
To assess the effectiveness and safety of aspirin for VTE prophylaxis after THR and TKR.
DATA SOURCES
A systematic review and meta-analysis was performed of randomized clinical trials (RCTs), with no language restrictions, from inception to September 19, 2019, using MEDLINE, Embase, Web of Science, Cochrane Library, and bibliographic searches. The computer-based searches combined terms and combinations of keywords related to the population (eg, hip replacement, knee replacement, hip arthroplasty, and knee arthroplasty), drug intervention (eg, aspirin, heparin, clexane, dabigatran, rivaroxaban, and warfarin), and outcome (eg, venous thromboembolism, deep vein thrombosis, pulmonary embolism, and bleeding) in humans.
STUDY SELECTION
This study included RCTs assessing the effectiveness and safety of aspirin for VTE prophylaxis compared with other anticoagulants in adults undergoing THR and TKR. The RCTs with a placebo control group were excluded. The searches and study selection were independently performed.
DATA EXTRACTION AND SYNTHESIS
This study followed PRISMA recommendations and used the Cochrane Collaboration's risk of bias tool. Data were screened and extracted independently by both reviewers. Study-specific relative risks (RRs) were aggregated using random-effects models. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach.
MAIN OUTCOMES AND MEASURES
The primary outcome was any postoperative VTE (asymptomatic or symptomatic). Secondary outcomes were adverse events associated with therapy, including bleeding.
RESULTS
Of 437 identified articles, 13 RCTs were included (6060 participants; 3466 [57.2%] women; mean age, 63.0 years). The RR of VTE after THR and TKR was 1.12 (95% CI, 0.78-1.62) for aspirin compared with other anticoagulants. Comparable findings were observed for deep vein thrombosis (DVT) (RR, 1.04; 95% CI, 0.72-1.51) and pulmonary embolism (PE) (RR, 1.01; 95% CI, 0.68-1.48). The risk of adverse events, including major bleeding, wound hematoma, and wound infection, was not statistically significantly different in patients receiving aspirin vs other anticoagulants. When analyzing THRs and TKRs separately, there was no statistically significant difference in the risk of VTE, DVT, and PE between aspirin and other anticoagulants. Aspirin had a VTE risk not statistically significantly different from low-molecular-weight heparin (RR, 0.76; 95% CI, 0.37-1.56) or rivaroxaban (RR, 1.52; 95% CI, 0.56-4.12). The quality of the evidence ranged from low to high.
CONCLUSIONS AND RELEVANCE
In terms of clinical effectiveness and safety profile, aspirin did not differ statistically significantly from other anticoagulants used for VTE prophylaxis after THR and TKR. Future trials should focus on noninferiority analysis of aspirin compared with alternative anticoagulants and cost-effectiveness.
Topics: Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Aspirin; Fibrinolytic Agents; Humans; Postoperative Complications; Treatment Outcome; Venous Thromboembolism
PubMed: 32011647
DOI: 10.1001/jamainternmed.2019.6108 -
Journal of the American College of... Jan 2023The efficacy and safety of direct oral anticoagulants (DOACs) for patients with thrombotic antiphospholipid syndrome remain controversial. (Meta-Analysis)
Meta-Analysis
BACKGROUND
The efficacy and safety of direct oral anticoagulants (DOACs) for patients with thrombotic antiphospholipid syndrome remain controversial.
OBJECTIVES
The authors performed a systematic review and meta-analysis of randomized controlled trials that compared DOACs with vitamin K antagonists (VKAs).
METHODS
We searched PubMed, EMBASE, and Cochrane Central Register of Controlled Trials through April 9, 2022. The 2 main efficacy outcomes were a composite of arterial thrombotic events and venous thromboembolic events (VTEs). The main safety outcome was major bleeding. Random effects models with inverse variance were used.
RESULTS
Our search retrieved 253 studies. Four open-label randomized controlled trials involving 472 patients were included (mean control-arm time-in-therapeutic-range 60%). All had proper random sequence generation and adequate allocation concealment. Overall, the use of DOACs compared with VKAs was associated with increased odds of subsequent arterial thrombotic events (OR: 5.43; 95% CI: 1.87-15.75; P < 0.001, I = 0%), especially stroke, and the composite of arterial thrombotic events or VTE (OR: 4.46; 95% CI: 1.12-17.84; P = 0.03, I = 0%). The odds of subsequent VTE (OR: 1.20; 95% CI: 0.31-4.55; P = 0.79, I = 0%), or major bleeding (OR: 1.02; 95% CI: 0.42-2.47; P = 0.97; I = 0%) were not significantly different between the 2 groups. Most findings were consistent within subgroups.
CONCLUSIONS
Patients with thrombotic antiphospholipid syndrome randomized to DOACs compared with VKAs appear to have increased risk for arterial thrombosis. No significant differences were observed between patients randomized to DOACs vs VKAs in the risk of subsequent VTE or major bleeding.
Topics: Humans; Administration, Oral; Anticoagulants; Antiphospholipid Syndrome; Fibrinolytic Agents; Hemorrhage; Randomized Controlled Trials as Topic; Thrombosis; Venous Thromboembolism; Vitamin K
PubMed: 36328154
DOI: 10.1016/j.jacc.2022.10.008 -
JAMA Network Open Oct 2023Sickle cell disease (SCD) is a monogenic disorder, yet clinical outcomes are influenced by additional genetic factors. Despite decades of research, the genetics of SCD... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Sickle cell disease (SCD) is a monogenic disorder, yet clinical outcomes are influenced by additional genetic factors. Despite decades of research, the genetics of SCD remain poorly understood.
OBJECTIVE
To assess all reported genetic modifiers of SCD, evaluate the design of associated studies, and provide guidelines for future analyses according to modern genetic study recommendations.
DATA SOURCES
PubMed, Web of Science, and Scopus were searched through May 16, 2023, identifying 5290 publications.
STUDY SELECTION
At least 2 reviewers identified 571 original, peer-reviewed English-language publications reporting genetic modifiers of human SCD phenotypes, wherein the outcome was not treatment response, and the comparison was not between SCD subtypes or including healthy controls.
DATA EXTRACTION AND SYNTHESIS
Data relevant to all genetic modifiers of SCD were extracted, evaluated, and presented following STREGA and PRISMA guidelines. Weighted z score meta-analyses and pathway analyses were conducted.
MAIN OUTCOMES AND MEASURES
Outcomes were aggregated into 25 categories, grouped as acute complications, chronic conditions, hematologic parameters or biomarkers, and general or mixed measures of SCD severity.
RESULTS
The 571 included studies reported on 29 670 unique individuals (50% ≤ 18 years of age) from 43 countries. Of the 17 757 extracted results (4890 significant) in 1552 genes, 3675 results met the study criteria for meta-analysis: reported phenotype and genotype, association size and direction, variability measure, sample size, and statistical test. Only 173 results for 62 associations could be cross-study combined. The remaining associations could not be aggregated because they were only reported once or methods (eg, study design, reporting practice) and genotype or phenotype definitions were insufficiently harmonized. Gene variants regulating fetal hemoglobin and α-thalassemia (important markers for SCD severity) were frequently identified: 19 single-nucleotide variants in BCL11A, HBS1L-MYB, and HBG2 were significantly associated with fetal hemoglobin (absolute value of Z = 4.00 to 20.66; P = 8.63 × 10-95 to 6.19 × 10-5), and α-thalassemia deletions were significantly associated with increased hemoglobin level and reduced risk of albuminuria, abnormal transcranial Doppler velocity, and stroke (absolute value of Z = 3.43 to 5.16; P = 2.42 × 10-7 to 6.00 × 10-4). However, other associations remain unconfirmed. Pathway analyses of significant genes highlighted the importance of cellular adhesion, inflammation, oxidative and toxic stress, and blood vessel regulation in SCD (23 of the top 25 Gene Ontology pathways involve these processes) and suggested future research areas.
CONCLUSIONS AND RELEVANCE
The findings of this comprehensive systematic review and meta-analysis of all published genetic modifiers of SCD indicated that implementation of standardized phenotypes, statistical methods, and reporting practices should accelerate discovery and validation of genetic modifiers and development of clinically actionable genetic profiles.
Topics: Humans; Fetal Hemoglobin; alpha-Thalassemia; Anemia, Sickle Cell; Genotype; Genetic Variation
PubMed: 37851445
DOI: 10.1001/jamanetworkopen.2023.37484 -
The Cochrane Database of Systematic... Apr 2023Deep vein thrombosis (DVT) is a condition in which a clot forms in the deep veins, most commonly of the leg. It occurs in approximately one in 1000 people. If left... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Deep vein thrombosis (DVT) is a condition in which a clot forms in the deep veins, most commonly of the leg. It occurs in approximately one in 1000 people. If left untreated, the clot can travel up to the lungs and cause a potentially life-threatening pulmonary embolism (PE). Previously, a DVT was treated with the anticoagulants heparin and vitamin K antagonists. However, two forms of direct oral anticoagulants (DOACs) have been developed: oral direct thrombin inhibitors (DTIs) and oral factor Xa inhibitors, which have characteristics that may be favourable compared to conventional treatment, including oral administration, a predictable effect, lack of frequent monitoring or dose adjustment and few known drug interactions. DOACs are now commonly being used for treating DVT: recent guidelines recommended DOACs over conventional anticoagulants for both DVT and PE treatment. This Cochrane Review was first published in 2015. It was the first systematic review to measure the effectiveness and safety of these drugs in the treatment of DVT. This is an update of the 2015 review. OBJECTIVES: To assess the effectiveness and safety of oral DTIs and oral factor Xa inhibitors versus conventional anticoagulants for the long-term treatment of DVT.
SEARCH METHODS
The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL databases and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 1 March 2022.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) in which people with a DVT, confirmed by standard imaging techniques, were allocated to receive an oral DTI or an oral factor Xa inhibitor compared with conventional anticoagulation or compared with each other for the treatment of DVT. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were recurrent venous thromboembolism (VTE), recurrent DVT and PE. Secondary outcomes included all-cause mortality, major bleeding, post-thrombotic syndrome (PTS) and quality of life (QoL). We used GRADE to assess the certainty of evidence for each outcome.
MAIN RESULTS
We identified 10 new studies with 2950 participants for this update. In total, we included 21 RCTs involving 30,895 participants. Three studies investigated oral DTIs (two dabigatran and one ximelagatran), 17 investigated oral factor Xa inhibitors (eight rivaroxaban, five apixaban and four edoxaban) and one three-arm trial investigated both a DTI (dabigatran) and factor Xa inhibitor (rivaroxaban). Overall, the studies were of good methodological quality. Meta-analysis comparing DTIs to conventional anticoagulation showed no clear difference in the rate of recurrent VTE (odds ratio (OR) 1.17, 95% confidence interval (CI) 0.83 to 1.65; 3 studies, 5994 participants; moderate-certainty evidence), recurrent DVT (OR 1.11, 95% CI 0.74 to 1.66; 3 studies, 5994 participants; moderate-certainty evidence), fatal PE (OR 1.32, 95% CI 0.29 to 6.02; 3 studies, 5994 participants; moderate-certainty evidence), non-fatal PE (OR 1.29, 95% CI 0.64 to 2.59; 3 studies, 5994 participants; moderate-certainty evidence) or all-cause mortality (OR 0.66, 95% CI 0.41 to 1.08; 1 study, 2489 participants; moderate-certainty evidence). DTIs reduced the rate of major bleeding (OR 0.58, 95% CI 0.38 to 0.89; 3 studies, 5994 participants; high-certainty evidence). For oral factor Xa inhibitors compared with conventional anticoagulation, meta-analysis demonstrated no clear difference in recurrent VTE (OR 0.85, 95% CI 0.71 to 1.01; 13 studies, 17,505 participants; moderate-certainty evidence), recurrent DVT (OR 0.70, 95% CI 0.49 to 1.01; 9 studies, 16,439 participants; moderate-certainty evidence), fatal PE (OR 1.18, 95% CI 0.69 to 2.02; 6 studies, 15,082 participants; moderate-certainty evidence), non-fatal PE (OR 0.93, 95% CI 0.68 to 1.27; 7 studies, 15,166 participants; moderate-certainty evidence) or all-cause mortality (OR 0.87, 95% CI 0.67 to 1.14; 9 studies, 10,770 participants; moderate-certainty evidence). Meta-analysis showed a reduced rate of major bleeding with oral factor Xa inhibitors compared with conventional anticoagulation (OR 0.63, 95% CI 0.45 to 0.89; 17 studies, 18,066 participants; high-certainty evidence). AUTHORS' CONCLUSIONS: The current review suggests that DOACs may be superior to conventional therapy in terms of safety (major bleeding), and are probably equivalent in terms of efficacy. There is probably little or no difference between DOACs and conventional anticoagulation in the prevention of recurrent VTE, recurrent DVT, pulmonary embolism and all-cause mortality. DOACs reduced the rate of major bleeding compared to conventional anticoagulation. The certainty of evidence was moderate or high.
Topics: Humans; Anticoagulants; Antithrombins; Factor Xa Inhibitors; Rivaroxaban; Dabigatran; Venous Thromboembolism; Neoplasm Recurrence, Local; Venous Thrombosis; Pulmonary Embolism; Hemorrhage
PubMed: 37058421
DOI: 10.1002/14651858.CD010956.pub3 -
The Cochrane Database of Systematic... May 2022Chronic obstructive pulmonary disease (COPD) is a chronic and progressive disease, often punctuated by recurrent flare-ups or exacerbations. Magnesium sulfate, having a... (Review)
Review
BACKGROUND
Chronic obstructive pulmonary disease (COPD) is a chronic and progressive disease, often punctuated by recurrent flare-ups or exacerbations. Magnesium sulfate, having a bronchodilatory effect, may have a potential role as an adjunct treatment in COPD exacerbations. However, comprehensive evidence of its effects is required to facilitate clinical decision-making.
OBJECTIVES
To assess the effects of magnesium sulfate for acute exacerbations of chronic obstructive pulmonary disease in adults.
SEARCH METHODS
We searched the Cochrane Airways Trials Register, CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, the World Health Organization (WHO) trials portal, EU Clinical Trials Register and Iranian Registry of Clinical Trials. We also searched the proceedings of major respiratory conferences and reference lists of included studies up to 2 August 2021.
SELECTION CRITERIA
We included single- or double-blind parallel-group randomised controlled trials (RCTs) assessing magnesium sulfate in adults with COPD exacerbations. We excluded cross-over trials.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. Two review authors independently selected trials for inclusion, extracted data and assessed risk of bias. The primary outcomes were: hospital admissions (from the emergency room); need for non-invasive ventilation (NIV), assisted ventilation or admission to intensive-care unit (ICU); and serious adverse events. Secondary outcomes were: length of hospital stay, mortality, adverse events, dyspnoea score, lung function and blood gas measurements. We assessed confidence in the evidence using GRADE methodology. For missing data, we contacted the study investigators.
MAIN RESULTS
We identified 11 RCTs (10 double-blind and 1 single-blind) with a total 762 participants. The mean age of participants ranged from 62 to 76 years. Trials were single- or two-centre trials conducted in Iran, New Zealand, Nepal, Turkey, the UK, Tunisia and the USA between 2004 and 2018. We judged studies to be at low or unclear risk of bias for most of the domains. Three studies were at high risk for blinding and other biases. Intravenous magnesium sulfate versus placebo Seven studies (24 to 77 participants) were included. Fewer people may require hospital admission with magnesium infusion compared to placebo (odds ratio (OR) 0.45, 95% CI 0.23 to 0.88; number needed to treat for an additional beneficial outcome (NNTB) = 7; 3 studies, 170 participants; low-certainty evidence). Intravenous magnesium may result in little to no difference in the requirement for non-invasive ventilation (OR 0.74, 95% CI 0.31 to 1.75; very low-certainty evidence). There were no reported cases of endotracheal intubation (2 studies, 107 participants) or serious adverse events (1 study, 77 participants) in either group. Included studies did not report intensive care unit (ICU) admission or deaths. Magnesium infusion may reduce the length of hospital stay by a mean difference (MD) of 2.7 days (95% CI 4.73 days to 0.66 days; 2 studies, 54 participants; low-certainty evidence) and improve dyspnoea score by a standardised mean difference of -1.40 (95% CI -1.83 to -0.96; 2 studies, 101 participants; low-certainty evidence). We were uncertain about the effect of magnesium infusion on improving lung function or oxygen saturation. For all adverse events, the Peto OR was 0.14 (95% CI 0.02 to 1.00; 102 participants); however, the event rate was too low to reach a robust conclusion. Nebulised magnesium sulfate versus placebo Three studies (20 to 172 participants) were included. Magnesium inhalation may have little to no impact on hospital admission (OR 0.77, 95% CI 0.21 to 2.82; very low-certainty evidence) or need for ventilatory support (NIV or mechanical ventilation) (OR 0.33, 95% CI 0.01 to 8.20; very low-certainty evidence). It may result in fewer ICU admissions compared to placebo (OR 0.39, 95% CI 0.15 to 1.00; very low-certainty evidence) and improvement in dyspnoea (MD -14.37, 95% CI -26.00 to -2.74; 1 study, 20 participants; very low-certainty evidence). There were no serious adverse events reported in either group. There was one reported death in the placebo arm in one trial, but the number of participants was too small for a conclusion. There was limited evidence about the effect of magnesium inhalation on length of hospital stay, lung function outcomes or oxygen saturation. Included studies did not report adverse events. Magnesium sulfate versus ipratropium bromide A single study with 124 participants assessed nebulised magnesium sulfate plus intravenous magnesium infusion versus nebulised ipratropium plus intravenous normal saline. There was little to no difference between these groups in terms of hospital admission (OR 1.62, 95% CI 0.78 to 3.37), endotracheal intubation (OR 1.69, 95% CI 0.61 to 4.71) and length of hospital stay (MD 1.10 days, 95% CI -0.22 to 2.42), all with very low-certainty evidence. There were no data available for non-invasive ventilation, ICU admission and serious adverse events. Adverse events were not reported. AUTHORS' CONCLUSIONS: Intravenous magnesium sulfate may be associated with fewer hospital admissions, reduced length of hospital stay and improved dyspnoea scores compared to placebo. There is no evidence of a difference between magnesium infusion and placebo for NIV, lung function, oxygen saturation or adverse events. We found no evidence for ICU admission, endotracheal intubation, serious adverse events or mortality. For nebulised magnesium sulfate, we are unable to draw conclusions about its effects in COPD exacerbations for most of the outcomes. Studies reported possibly lower ICU admissions and a lesser degree of dyspnoea with magnesium inhalation compared to placebo; however, larger studies are required to yield a more precise estimate for these outcomes. Similarly, we could not identify any robust evidence for magnesium sulfate compared to ipratropium bromide. Future well-designed multicentre trials with larger samples are required, including subgroups according to severity of exacerbations and COPD phenotypes.
Topics: Disease Progression; Dyspnea; Humans; Ipratropium; Magnesium; Magnesium Sulfate; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic
PubMed: 35616126
DOI: 10.1002/14651858.CD013506.pub2