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Clinical Cardiology Sep 2021To assess the risk of gastrointestinal bleeding and intracranial hemorrhage in patients with atrial fibrillation (AF) after the use of rivaroxaban or warfarin. To... (Meta-Analysis)
Meta-Analysis Review
Effects of rivaroxaban and warfarin on the risk of gastrointestinal bleeding and intracranial hemorrhage in patients with atrial fibrillation: Systematic review and meta-analysis.
To assess the risk of gastrointestinal bleeding and intracranial hemorrhage in patients with atrial fibrillation (AF) after the use of rivaroxaban or warfarin. To investigate the effects of rivaroxaban and warfarin on gastrointestinal and intracranial hemorrhage in patients with AF, we searched PubMed, Embase, and Medline from the establishment of databases up to 2020. We finally included 38 observational studies involving 1 312 609 patients for the assessment of intracranial hemorrhage, and 33 observational studies involving 1 332 956 patients for the assessment of gastrointestinal bleeding. The rates of intracranial hemorrhage were 0.55% in the rivaroxaban group versus 0.91% in the warfarin group (OR 0.59; 95% CI 0.53-0.66; p < .00001, I2 = 78%). The rates of gastrointestinal bleeding were 2.63% in patients with rivaroxaban versus 2.48% in those with warfarin (OR 1.06; 95% CI 0.96-1.17; p < .00001, I2 = 94%). Rivaroxaban could significantly reduce the risk of intracranial hemorrhage in patients with AF than warfarin, but the risk of gastrointestinal bleeding remained controversy due to no statistical significant difference. Notably, a subgroup analysis demonstrated that patients in rivaroxaban group with severe chronic renal diseases or undergoing hemodialysis exposed to less gastrointestinal hemorrhage risk than the group from warfarin.
Topics: Anticoagulants; Atrial Fibrillation; Dabigatran; Gastrointestinal Hemorrhage; Humans; Intracranial Hemorrhages; Rivaroxaban; Stroke; Warfarin
PubMed: 34302375
DOI: 10.1002/clc.23690 -
Cardiovascular Therapeutics 2021The guidelines on antithrombotic treatment in patients with symptomatic peripheral artery disease (PAD) undergoing peripheral revascularization of the lower extremities... (Meta-Analysis)
Meta-Analysis Review
Efficacy and Safety of Rivaroxaban Compared with Other Therapies Used in Patients with Peripheral Artery Disease Undergoing Peripheral Revascularization: A Systematic Literature Review and Network Meta-Analysis.
BACKGROUND
The guidelines on antithrombotic treatment in patients with symptomatic peripheral artery disease (PAD) undergoing peripheral revascularization of the lower extremities were developed based on heterogeneous trials, assessing various dose regimens and recruiting patients who were subjected to different revascularization procedures.
OBJECTIVE
To compare efficacy and safety of treatments used in patients with PAD undergoing peripheral revascularization accounting for between-trial heterogeneity and large dispersion of the quality of evidence.
METHODS
A systematic literature review of randomised controlled trials (RCTs) recruiting adult patients with PAD receiving antithrombotics was conducted until January 2020. Hazard ratios (HR) were pooled using Bayesian network meta-analysis. The estimated between-treatment effects were presented as HR together with 95% credible intervals. The base case analysis included studies recruiting patients following recent peripheral revascularization, who received treatment regimens administered within the recommended therapeutic window, while a sensitivity scenario included all identified trials.
RESULTS
Thirteen RCTs were identified (8 RCTs enrolled patients following peripheral revascularization and 5 RCTs regardless of the previous revascularization). Five trials, recruiting an overall of 8349 patients, were considered for the base case analysis. Of those, 6564 patients were recruited in the VOYAGER PAD trial comparing rivaroxaban plus aspirin (RIV plus ASA) versus ASA. RIV plus ASA was associated with a lower risk of repeated peripheral revascularization versus ASA monotherapy (HR = 0.88 [0.79, 0.99]), however having a trend towards an increased rate of major bleeding (HR = 1.43 [0.98, 2.11]). There was no evidence for differences between RIV plus ASA and dual antiplatelet therapy and vitamin K antagonists plus ASA. Similar results were observed in sensitivity analyses.
CONCLUSIONS
RIV plus ASA is associated with reduced risk of revascularization compared with ASA monotherapy, but the evidence for other comparators, in particular antiplatelet regimens, was insufficient to guide treatment decisions and highlights the challenge in establishing the magnitude of comparative efficacy using existing RCTs.
Topics: Adult; Aspirin; Humans; Network Meta-Analysis; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Rivaroxaban
PubMed: 34497668
DOI: 10.1155/2021/8561350 -
Seminars in Thrombosis and Hemostasis Sep 2021Venous thromboembolism (VTE) in children can lead to significant morbidity and mortality. Traditionally, treatment for thrombotic events in pediatric patients has been...
Efficacy and Safety of Non-Vitamin K Antagonist Oral Anticoagulants in Pediatric Venous Thromboembolism Treatment and Thromboprophylaxis: A Systematic Review of the Literature.
Venous thromboembolism (VTE) in children can lead to significant morbidity and mortality. Traditionally, treatment for thrombotic events in pediatric patients has been limited mainly to unfractionated heparin, low-molecular-weight heparin (LMWH), or vitamin K antagonists. Since the first non-vitamin K antagonist oral anticoagulant (NOAC) was approved for adult use, these agents have gained popularity for a variety of indications. This is largely due to their ease of administration, favorable pharmacokinetic and pharmacodynamic profile, decreased food interactions, and decreased need for therapeutic drug monitoring. Treating and preventing VTE with traditional anticoagulants in pediatric patients presents many challenges. This systematic review evaluated the current literature regarding pediatric NOAC trials. Additionally, based on an up-to-date query of , we detail current ongoing and as-yet unpublished clinical trials, study outcomes, and projected completion dates. Published pediatric NOAC trials have included 1,007 total children to date and have ranged from phase 1 to 4, with "indications" including both thromboembolism prophylaxis and VTE treatment. Three recent phase 3 trials, specifically involving rivaroxaban and dabigatran, have shown the agents to be at least as effective as traditional anticoagulants for acute and/or extended VTE treatment, with low frequency of recurrent thrombosis and clinically significant bleeding rates. Additionally, specially developed and tested pediatric formulations have allowed for accurate and reliable dosing, oral administration, stable pharmacokinetics and pharmacodynamics, and fewer drug or food interactions. Ongoing trials, anticipated for completion in the next few years, will reveal important information with regard to thromboembolism prophylaxis in special pediatric subpopulations and settings.
Topics: Administration, Oral; Adult; Anticoagulants; Child; Heparin; Heparin, Low-Molecular-Weight; Humans; Rivaroxaban; Venous Thromboembolism
PubMed: 33971679
DOI: 10.1055/s-0041-1725944 -
Injury Dec 2023Venous thromboembolism (VTE) is a major complication of trauma. Currently, there are few studies summarising the evidence for prophylaxis in trauma settings. This review... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Venous thromboembolism (VTE) is a major complication of trauma. Currently, there are few studies summarising the evidence for prophylaxis in trauma settings. This review provides evidence for the use of VTE prophylactic interventions in trauma patients to produce evidence-based guidelines.
METHODS
A PRISMA-compliant review was conducted from Sep 2021 to June 2023, using Embase, Medline and Google Scholar. The inclusion criteria were: randomized-controlled trials (RCTs) in English published after 2000 of adult trauma patients comparing VTE prophylaxis interventions, with a sample size higher than 20. The network analysis was conducted using RStudio. The results of the pairwise comparisons were presented in the form of a league table. The quality of evidence and heterogeneity sensitivity were assessed. The primary outcome focused on venous thromboembolism (VTE), and examined deep vein thrombosis (DVT) and pulmonary embolism (PE) as separate entities. The secondary outcomes included assessments of bleeding and mortality. PROSPERO registration: CRD42021266393.
RESULTS
Of the 7,948 search results, 23 studies with a total of 21,312 participants fulfilled screening criteria, which included orthopaedic, spine, solid organ, brain, spinal cord, and multi-region trauma. Of the eight papers comparing chemical prophylaxis medications in patients with hip or lower limb injuries, fondaparinux and enoxaparin were found to be significantly superior to placebo in respect of prevention of DVT, with no increased risk of bleeding. Regarding mechanical prophylaxis, meta-analysis of two studies of inferior vena cava filters failed to provide significant benefits to major trauma patients.
CONCLUSION
Enoxaparin and fondaparinux are safe and effective options for VTE prevention in trauma patients, with fondaparinux being a cheaper and easier administration option between the two. Inconclusive results were found in mechanical prophylaxis, requiring more larger-scale RCTs.
Topics: Adult; Humans; Venous Thromboembolism; Enoxaparin; Fondaparinux; Network Meta-Analysis; Anticoagulants; Pulmonary Embolism; Hemorrhage; Multiple Trauma
PubMed: 37865011
DOI: 10.1016/j.injury.2023.111078 -
Journal of General Internal Medicine Sep 2020Infection with coronavirus SARS-CoV-2, causing COVID-19 disease, leads to inflammation and a prothrombotic state.
BACKGROUND
Infection with coronavirus SARS-CoV-2, causing COVID-19 disease, leads to inflammation and a prothrombotic state.
OBJECTIVE
This rapid systematic review aims to synthesize evidence on thromboembolism incidence and outcomes with antithrombotic therapies in COVID-19.
DATA SOURCES
We searched MEDLINE (Ovid), Cochrane Rapid Reviews, PROSPERO, and the WHO COVID-19 Database from January 1, 2003, to April 22, 2020, for studies meeting pre-specified inclusion criteria.
STUDY SELECTION, DATA EXTRACTION, AND SYNTHESIS
One investigator identified articles for inclusion, abstracted data, and performed quality assessment, with second reviewer checking.
RESULTS
Incidence of thromboembolism among hospitalized patients with COVID-19 ranged from 25 to 53% in 4 retrospective series. We identified 3 studies (1 retrospective cohort study, 1 prospective uncontrolled observational study, and 1 case series) examining outcomes among COVID-19 patients who received antithrombotic therapies. These studies all included different interventions (thromboprophylaxis with unfractionated heparin (UFH) or low molecular-weight heparin (LMWH); an intensive thromboprophylaxis protocol with LMWH, antithrombin, and clopidogrel; and salvage therapy with tissue plasminogen activator and heparin). These studies are overall poor quality due to methodological limitations including unclear patient selection protocols, lack of reporting or adjustment for patient baseline characteristics, inadequate duration of follow-up, and partial reporting of outcomes.
CONCLUSIONS
New evidence on thromboembolism in COVID-19 does not warrant a change in current guidance on thromboprophylaxis among hospitalized patients. Prospective trials of antithrombotic treatment strategies among patients with COVID-19 are urgently needed.
Topics: Anticoagulants; Betacoronavirus; COVID-19; Coronavirus Infections; Fibrinolytic Agents; Humans; Observational Studies as Topic; Pandemics; Pneumonia, Viral; Prospective Studies; Retrospective Studies; SARS-CoV-2; Venous Thromboembolism
PubMed: 32556875
DOI: 10.1007/s11606-020-05906-y -
Thrombosis Research Mar 2020Direct oral anticoagulants (DOACs) are now the first choice thromboprophylaxis in cancer patients who do not have a high risk of bleeding. In addition to the... (Review)
Review
BACKGROUND
Direct oral anticoagulants (DOACs) are now the first choice thromboprophylaxis in cancer patients who do not have a high risk of bleeding. In addition to the anticoagulant effects, potential anti-tumor effects of DOACs have also been studied in animal cancer models. In this study, we summarize the effects of DOACs on cancer growth and metastasis in animal models through a systematic review with a qualitative analysis.
METHODS
PubMed, EMBASE and Web of Science were systematically searched for original studies that describe animal models of cancer in which one of the experimental groups received DOAC monotherapy, and which reported quantitatively on primary tumor or metastases.
RESULTS
Nine studies - reporting a total of 19 animal experiments - met the inclusion criteria. These 19 experiments included spontaneous cancer (n = 2), carcinogenicity (n = 2), xenograft (n = 7) and syngeneic (n = 8) models, encompassing orthotopic (n = 7), subcutaneous (n = 5), intraperitoneal (n = 1) and intravenous (n = 2) injection of cancer cells and included treatments with the DOACs ximelagatran (n = 4), dabigatran etexilate (n = 6) and/or rivaroxaban (n = 11). DOAC treatment decreased tumor growth at implanted and metastatic site in 18.8% (3/16) and 20.0% (3/15) of the experiments, respectively. Conversely, DOACs increased tumor growth at implanted and metastatic site in 6.3% (1/16) and 20.0% (3/15) of the experiments, respectively.
CONCLUSION
DOAC monotherapy resulted in neoplastic changes in a rat carcinogenicity study, showed a lack of effect in mouse xenograft models, while the effect on cancer growth and metastasis in mouse syngeneic models depended on the timing of DOAC treatment and type of cancer model used.
Topics: Administration, Oral; Animals; Anticoagulants; Antithrombins; Dabigatran; Humans; Mice; Models, Animal; Neoplasms; Pyrazoles; Pyridones; Rats; Rivaroxaban; Venous Thromboembolism
PubMed: 31945588
DOI: 10.1016/j.thromres.2019.12.022 -
Aging Aug 2020The ongoing outbreak of Coronavirus Disease 2019 (COVID-19) is hitting the world hard, but the relationship between coagulation disorders and COVID-19 is still not... (Meta-Analysis)
Meta-Analysis
The ongoing outbreak of Coronavirus Disease 2019 (COVID-19) is hitting the world hard, but the relationship between coagulation disorders and COVID-19 is still not clear. This study aimed to explore whether early coagulation tests can predict risk stratification and prognosis. PubMed, Web of Science, Cochrane Library, and Scopus were searched electronically for relevant research studies published up to March 24, 2020, producing 24 articles for the final inclusion. The pooled standard mean difference (SMD) of coagulation parameters at admission were calculated to determine severe and composite endpoint conditions (ICU or death) in COVID-19 patients. Meta-analyses revealed that platelet count was not statistically related to disease severity and composite endpoint; elevated D-dimer correlated positively with disease severity (SMD 0.787 (0.277-1.298), P= 0.003, I= 96.7%) but had no significant statistical relationship with composite endpoints. Similarly, patients with prolonged prothrombin time (PT) had an increased risk of ICU and increased risk of death (SMD 1.338 (0.551-2.125), P = 0.001, I = 92.7%). Besides, increased fibrin degradation products (FDP) and decreased antithrombin might also mean the disease is worsening. Therefore, early coagulation tests followed by dynamic monitoring is useful for recognizing coagulation disorders accompanied by COVID-19 and guiding timely therapy to improve prognosis.
Topics: Betacoronavirus; Blood Coagulation Tests; COVID-19; Coronavirus Infections; Early Diagnosis; Humans; Pandemics; Pneumonia, Viral; Prognosis; Risk Assessment; SARS-CoV-2; Severity of Illness Index
PubMed: 32860672
DOI: 10.18632/aging.103581 -
The Cochrane Database of Systematic... May 2021People with chronic heart failure (HF) are at risk of thromboembolic events, including stroke, pulmonary embolism, and peripheral arterial embolism; coronary ischaemic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
People with chronic heart failure (HF) are at risk of thromboembolic events, including stroke, pulmonary embolism, and peripheral arterial embolism; coronary ischaemic events also contribute to the progression of HF. The use of long-term oral anticoagulation is established in certain populations, including people with HF and atrial fibrillation (AF), but there is wide variation in the indications and use of oral anticoagulation in the broader HF population.
OBJECTIVES
To determine whether long-term oral anticoagulation reduces total deaths and stroke in people with heart failure in sinus rhythm.
SEARCH METHODS
We updated the searches in CENTRAL, MEDLINE, and Embase in March 2020. We screened reference lists of papers and abstracts from national and international cardiovascular meetings to identify unpublished studies. We contacted relevant authors to obtain further data. We did not apply any language restrictions.
SELECTION CRITERIA
Randomised controlled trials (RCT) comparing oral anticoagulants with placebo or no treatment in adults with HF, with treatment duration of at least one month. We made inclusion decisions in duplicate, and resolved any disagreements between review authors by discussion, or a third party.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trials for inclusion, and assessed the risks and benefits of antithrombotic therapy by calculating odds ratio (OR), accompanied by the 95% confidence intervals (CI).
MAIN RESULTS
We identified three RCTs (5498 participants). One RCT compared warfarin, aspirin, and no antithrombotic therapy, the second compared warfarin with placebo in participants with idiopathic dilated cardiomyopathy, and the third compared rivaroxaban with placebo in participants with HF and coronary artery disease. We pooled data from the studies that compared warfarin with a placebo or no treatment. We are uncertain if there is an effect on all-cause death (OR 0.66, 95% CI 0.36 to 1.18; 2 studies, 324 participants; low-certainty evidence); warfarin may increase the risk of major bleeding events (OR 5.98, 95% CI 1.71 to 20.93, NNTH 17). 2 studies, 324 participants; low-certainty evidence). None of the studies reported stroke as an individual outcome. Rivaroxaban makes little to no difference to all-cause death compared with placebo (OR 0.99, 95% CI 0.87 to 1.13; 1 study, 5022 participants; high-certainty evidence). Rivaroxaban probably reduces the risk of stroke compared to placebo (OR 0.67, 95% CI 0.47 to 0.95; NNTB 101; 1 study, 5022 participants; moderate-certainty evidence), and probably increases the risk of major bleeding events (OR 1.65, 95% CI 1.17 to 2.33; NNTH 79; 1 study, 5008 participants; moderate-certainty evidence).
AUTHORS' CONCLUSIONS
Based on the three RCTs, there is no evidence that oral anticoagulant therapy modifies mortality in people with HF in sinus rhythm. The evidence is uncertain if warfarin has any effect on all-cause death compared to placebo or no treatment, but it may increase the risk of major bleeding events. There is no evidence of a difference in the effect of rivaroxaban on all-cause death compared to placebo. It probably reduces the risk of stroke, but probably increases the risk of major bleedings. The available evidence does not support the routine use of anticoagulation in people with HF who remain in sinus rhythm.
Topics: Administration, Oral; Anticoagulants; Aspirin; Cardiomyopathy, Dilated; Chronic Disease; Heart Failure; Heart Rate; Hemorrhage; Humans; Placebo Effect; Placebos; Randomized Controlled Trials as Topic; Rivaroxaban; Stroke; Thromboembolism; Warfarin
PubMed: 34002371
DOI: 10.1002/14651858.CD003336.pub4 -
European Review For Medical and... Aug 2022Previous preliminary clinical trials have confirmed that edoxaban can be efficacious for venous thromboembolism (VTE). This meta-analysis was considered to evaluate... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Previous preliminary clinical trials have confirmed that edoxaban can be efficacious for venous thromboembolism (VTE). This meta-analysis was considered to evaluate edoxaban's short-term efficacy and safety for venous thromboembolism after arthroplasty.
MATERIALS AND METHODS
A comprehensive search was performed in these databases: PubMed, MEDLINE, Web of Science, and EMBASE on March 2022. All eligible trials should be randomized controlled trials (RCTs) when evaluating short-term efficacy and safety outcomes of edoxaban for VTE after total hip or knee arthroplasty.
RESULTS
Nine RCTs with 4274 patients were involved in this meta-analysis. Edoxaban in the VTE group prevented the incidence of VTE and indicated valuable clinical efficacy. The incidence of adverse events (AEs) and adverse drug reactions (ADRs) in the edoxaban group was decreased than that in other groups. Edoxaban increased the incidence of all bleeding events. However, in the edoxaban group and other groups, there was no statistical difference between major bleeding events and clinically relevant non-major or minor bleeding events. Edoxaban subgroups included edoxaban 15 mg, edoxaban 30 mg and edoxaban 60 mg prevented the incidence of VTE. Edoxaban 30 mg and 60 mg group increased the risk of all bleeding events. Edoxaban 30 mg can increase the incidence of major bleeding events. There was no difference in clinically relevant non-major or minor bleeding events. Edoxaban 30 mg can decrease the incidence of AEs.
CONCLUSIONS
Edoxaban was an efficacious and safe option to prevent and treat VTE in patients undergoing arthroplasty. However, we need further trials to explore edoxaban's long-term efficacy and safety.
Topics: Anticoagulants; Arthroplasty, Replacement, Knee; Hemorrhage; Humans; Pyridines; Thiazoles; Venous Thromboembolism
PubMed: 35993651
DOI: 10.26355/eurrev_202208_29425 -
PLoS Medicine Jul 2022Lower limb trauma requiring immobilization is a significant contributor to overall venous thromboembolism (VTE) burden. The clinical effectiveness of thromboprophylaxis... (Meta-Analysis)
Meta-Analysis
Prevention of venous thromboembolic events in patients with lower leg immobilization after trauma: Systematic review and network meta-analysis with meta-epsidemiological approach.
BACKGROUND
Lower limb trauma requiring immobilization is a significant contributor to overall venous thromboembolism (VTE) burden. The clinical effectiveness of thromboprophylaxis for this indication and the optimal agent strategy are still a matter of debate. Our main objective was to assess the efficacy of pharmacological thromboprophylaxis to prevent VTE in patients with isolated temporary lower limb immobilization after trauma. We aimed to estimate and compare the clinical efficacy and the safety of the different thromboprophylactic treatments to determine the best strategy.
METHODS AND FINDINGS
We conducted a systematic review and a Bayesian network meta-analysis (NMA) including all available randomized trials comparing a pharmacological thromboprophylactic treatment to placebo or to no treatment in patients with leg immobilization after trauma. We searched Medline, Embase, and Web of Science until July 2021. Only RCT or observational studies with analysis of confounding factors including adult patients requiring temporary immobilization for an isolated lower limb injury treated conservatively or surgically and assessing pharmacological thromboprophylactic agents or placebo or no treatment were eligible for inclusion. The primary endpoint was the incidence of major VTE (proximal deep vein thrombosis, symptomatic VTE, and pulmonary embolism-related death). We extracted data according to Preferred Reporting Items for Systematic Reviews and Meta-analyses for NMA and appraised selected trials with the Cochrane review handbook. Fourteen studies were included (8,198 patients). Compared to the control group, rivaroxaban, fondaparinux, and low molecular weight heparins were associated with a significant risk reduction of major VTE with an odds ratio of 0.02 (95% credible interval (CrI) 0.00 to 0.19), 0.22 (95% CrI 0.06 to 0.65), and 0.32 (95% CrI 0.15 to 0.56), respectively. No increase of the major bleeding risk was observed with either treatment. Rivaroxaban has the highest likelihood of being ranked top in terms of efficacy and net clinical benefit. The main limitation is that the network had as many indirect comparisons as direct comparisons.
CONCLUSIONS
This NMA confirms the favorable benefit/risk ratio of thromboprophylaxis for patients with leg immobilization after trauma with the highest level of evidence for rivaroxaban.
TRIAL REGISTRATION
PROSPERO CRD42021257669.
Topics: Adult; Anticoagulants; Bayes Theorem; Humans; Leg; Lower Extremity; Network Meta-Analysis; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis
PubMed: 35849624
DOI: 10.1371/journal.pmed.1004059