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Annals of Medicine and Surgery (2012) Apr 2024Cerebral venous thromboembolism (CVT) poses a significant risk of venous infarction and haemorrhage, which can lead to neurological deficits and, in severe cases, even... (Review)
Review
BACKGROUND
Cerebral venous thromboembolism (CVT) poses a significant risk of venous infarction and haemorrhage, which can lead to neurological deficits and, in severe cases, even death. The optimal treatment regimen for patients with CVT remains unclear.
METHODS
MEDLINE, Embase, Google Scholar, Web of Science (WoS), and Cochrane Central databases were searched for randomized controlled trials (RCTs) and observational studies assessing the efficacy and safety of rivaroxaban in patients with CVT. All-site venous thromboembolism (VTE), risk of clinically relevant non-major bleeding, incidence of partial recanalization, complete recanalization and major haemorrhage were among outcomes of interest. Mantel-Haenszel weighted random-effects model was used to calculate relative risks (RRs) with 95% CIs.
RESULTS
The analysis included 1 RCT and 3 observational studies containing 211 patients. Compared to vitamin K antagonists (VKAs), rivaroxaban did not significantly decrease the all-site VTE [RR 0.31 (95% CI 0.01, 8.43); =0.49, I=0%]. Compared with VKAs, patients on rivaroxaban did not show a significantly reduced risk of recurrent cerebral venous thrombosis. In terms of incidence of partial recanalization, there was no discernible difference between rivaroxaban and VKAs [RR 0.90 (95% CI 0.66, 1.22); =0.49, I=0%]. There was no discernible difference in incidence of complete recanalization [RR 0.98 (95% CI 0.32, 3.03); =0.97, I=28%] and incidence of major haemorrhage [RR 0.19 (95% CI 0.01, 4.54); =0.30].
CONCLUSION
Rivaroxaban was found to have similar efficacy to VKAs. Due to its lower risk of severe bleeding and no need for INR monitoring, rivaroxaban may be a preferable treatment option for CVT.
PubMed: 38576935
DOI: 10.1097/MS9.0000000000001689 -
Medicine Dec 2023A systematic review and network meta-analysis (NMA) were conducted to explore the efficacy and safety of different antiplatelet or anticoagulation drugs in chronic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
A systematic review and network meta-analysis (NMA) were conducted to explore the efficacy and safety of different antiplatelet or anticoagulation drugs in chronic coronary syndromes patients.
METHODS
Electronic databases (Pubmed, Embase and Cochrane databases) were systematically searched to identify randomized controlled trials evaluating different antiplatelet or anticoagulation drugs (aspirin, aspirin + clopidogrel, aspirin + clopidogrel + cilostazol, clopidogrel/prasugrel + aspirin, aspirin + rivaoxaban 2.5 mg, aspirin + ticagrelor 60 mg, aspirin + ticagrelor 90 mg, clopidogrel or rivroxaban 5 mg) versus placebo for treatment chronic coronary syndromes patients. Outcomes included major adverse cardiovascular events, all cause death, major bleeding and myocardial infarction. A random-effect Bayesian NMA was conducted for outcomes of interest, and results were presented as odds ratios (ORs) and 95% credible intervals. The NMA was performed using R Software with a GeMTC package. A Bayesian NMA was performed and relative ranking of agents was assessed using surface under the cumulative ranking probabilities.
RESULTS
Ten randomized controlled trials met criteria for inclusion and finally included in this NMA. In head-to-head comparison, no significant difference was observed between all antithrombotic treatment strategies with respect to primary endpoint of major adverse cardiovascular events. In head-to-head comparison, no significant difference was observed between all antithrombotic treatment strategies with respect to all cause death. Clopidogrel/prasugrel + aspirin (OR = 3.8, 95% credible intervals [CrI]: 1.3-12.0, P < .05) and aspirin + rivaroxaban 2.5 mg (OR = 3.1, 95%CrI: 1.1-9.5, P < .05) was associated with an increase of the major bleeding. Compared with aspirin alone, aspirin + clopidogrel (OR = 0.42, 95%CrI: 0.22-0.76, P < .05) and aspirin + ticagrelor 90 mg (OR = 0.42, 95%CrI: 0.17-0.95, P < .05) was associated with a decrease of the myocardial infarction.
CONCLUSIONS
Myocardial infarction was significantly lower when adding clopidogrel or ticagrelor 90 mg to aspirin than those in the aspirin alone group. However, clopidogrel/prasugrel and rivaroxaban 2.5 mg was associated with an increase of the major bleeding than aspirin alone.
Topics: Humans; Clopidogrel; Platelet Aggregation Inhibitors; Ticagrelor; Prasugrel Hydrochloride; Rivaroxaban; Network Meta-Analysis; Bayes Theorem; Fibrinolytic Agents; Aspirin; Myocardial Infarction; Hemorrhage; Anticoagulants; Acute Coronary Syndrome; Treatment Outcome
PubMed: 38050293
DOI: 10.1097/MD.0000000000036429 -
European Journal of Vascular and... Nov 2014The aim was to perform a review of the efficacy and safety of new oral anticoagulants (NOAs) in the management of venous thromboembolism (VTE). (Meta-Analysis)
Meta-Analysis Review
Editor's Choice - efficacy and safety of the new oral anticoagulants dabigatran, rivaroxaban, apixaban, and edoxaban in the treatment and secondary prevention of venous thromboembolism: a systematic review and meta-analysis of phase III trials.
OBJECTIVES
The aim was to perform a review of the efficacy and safety of new oral anticoagulants (NOAs) in the management of venous thromboembolism (VTE).
METHODS
This was a systematic review and meta-analysis. On March 26, 2014, Medline, Embase, and the Cochrane trial register were searched for randomized controlled trials (RCTs) comparing the NOAs dabigatran, rivaroxaban, apixaban, and edoxaban with vitamin K antagonists (VKAs) in VTE treatment and secondary prevention. Two investigators assessed the methodological quality of the RCTs. The main study outcomes (efficacy, safety and net clinical benefit) were expressed as risk ratios (RR) with 95% confidence interval (CI).
RESULTS
Ten RCTs, mostly with low risk of bias, with nearly 38,000 patients, were identified. In six trials of treatment, NOAs were equally effective as VKAs in preventing recurrent symptomatic VTE (RR 0.89, 95% CI 0.75-1.05), but major bleeding occurred less often (1.08% vs. 1.73% for VKAs, RR 0.63, 95% CI 0.51-0.77), leading net clinical benefit to favor NOAs (RR 0.79, 95% CI 0.70-0.90). Fatal bleeding occurred less often with NOAs (0.09% vs. 0.18% for VKAs), a difference that approached statistical significance (RR 0.51, 95% CI 0.26-1.01). In three secondary prevention trials, NOAs reduced VTE recurrence rates to 1.32% (vs. 7.24% with placebo, RR 0.17, 95% CI 0.12-0.24) and fatal pulmonary embolism (PE) (including unexplained deaths) to 0.1% (vs. 0.29% for placebo, RR 0.37, 95% CI 0.10-1.38) at the expense of clinically relevant non-major bleeding (4.3% vs. 1.8% for placebo, RR 2.32, 95% CI 1.65-3.35), but not major bleeding. All-cause mortality rate was reduced to 0.41% with NOAs (vs. 0.86% with placebo, RR 0.38, 95% CI 0.18-0.79). Net clinical benefit favored NOAs (RR 0.21, 95% CI 0.15-0.29), and NNT was 18.
CONCLUSIONS
Compared to VKAs, NOAs are not only effective in treating VTE but also safer in terms of bleeding, thereby conferring clinical benefit. Their safety and efficacy was confirmed further in secondary prevention trials.
Topics: Administration, Oral; Anticoagulants; Benzimidazoles; Clinical Trials, Phase III as Topic; Dabigatran; Humans; Morpholines; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Secondary Prevention; Thiazoles; Thiophenes; Venous Thromboembolism; beta-Alanine
PubMed: 24951377
DOI: 10.1016/j.ejvs.2014.05.001 -
Frontiers in Cardiovascular Medicine 2023Nowadays, the number of patients with non-valvular atrial fibrillation (NVAF) complicated by end-stage renal disease (ESKD) is increasing. There are significant...
BACKGROUND
Nowadays, the number of patients with non-valvular atrial fibrillation (NVAF) complicated by end-stage renal disease (ESKD) is increasing. There are significant challenges in anticoagulation with prescription drugs because of the high risk of bleeding and embolism among these patients. However, no randomized controlled trials (RCTs) of warfarin in combination with any non-vitamin K oral anticoagulant (NOACs) have been performed in patients with baseline creatinine clearance (CrCl) <25 ml/min, which makes it difficult to justify the use of anticoagulants in such patients. Then, we aimed to collect and summarize all evidence to enable the anticoagulation of rivaroxaban, which is less cleared by the kidneys, in patients with severe renal insufficiency and to complement and improve the evidence on the use of rivaroxaban for anticoagulation.
METHODS
The present systematic review and meta-analysis searched the databases of , , the , , , and for relevant studies from inception to 1 June 2022, with the restriction of English and Chinese. Eligible cohort studies and RCTs that reported efficacy outcomes [composite of stroke and systemic embolism (SSE), ischemic stroke (ICS), and systemic embolization] or safety outcomes [major bleeding, intracranial hemorrhage (ICH), and gastrointestinal bleeding (GIB)] of rivaroxaban in NVAF patients with ESKD were enrolled. Two authors completed the data extraction and quality assessment work, respectively. The Cochrane Collaboration tool for assessing the risk of bias was used for RCTs, and the NEW-Castle Ottawa scale was used for study quality assessment for cohort studies. Dichotomous variables were calculated as risk factors with 95% confidence intervals (CIs), and meta-analysis was performed to probe the effect of research design, rivaroxaban dose, and controlled drug factors on outcomes.
RESULTS
In total, three studies were included for meta-analysis, involving 6,071 NVAF patients with ESKD, and two studies were included for qualitative analysis. All included studies were at low risk of bias. A meta-analysis demonstrated that mix-dose rivaroxaban caused no statistical discrepancy in the occurrence of thrombotic and bleeding events when compared to the control group (embolism, LogOR: -0.64, 95% CI: -1.05 to -0.23, P:0.25; bleeding, LogOR: -0.33, 95% CI: -0.63 to -0.03, P:0.15), and low-dose rivaroxaban produced similar results (embolism, LogOR: -1.04, 95% CI: -2.15 to 0.07, P:0.61; bleeding, LogOR: -0.81, 95% CI: -1.19 to -0.44, P:0.93).
CONCLUSION
In this study, low-dose rivaroxaban (10 mg, once a day) may benefit more than warfarin in patients with NVAF and ESKD.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/#recordDetails, identifier CRD42022330973.
PubMed: 36844734
DOI: 10.3389/fcvm.2023.1021959 -
Frontiers in Pharmacology 2023A lack of clarity persists regarding the efficacy and risks associated with direct oral anticoagulants (DOACs) in end-stage renal disease (ESRD) patients with atrial...
A lack of clarity persists regarding the efficacy and risks associated with direct oral anticoagulants (DOACs) in end-stage renal disease (ESRD) patients with atrial fibrillation (AF) undergoing dialysis, primarily due to limited retrospective studies. Therefore, the objective of this study was to evaluate the existing data and propose a practical protocol for the clinical utilization of DOACs in ESRD patients with AF undergoing dialysis. PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials were searched for clinical studies evaluating DOACs in ESRD patients with AF on dialysis published up to 2 February 2023. DOACs included warfarin, dabigatran, apixaban, edoxaban, and rivaroxaban. The outcomes were mortality, ischemic stroke, hemorrhagic stroke, any stroke, gastrointestinal bleeding, major bleeding, intracranial bleeding, and minor bleeding. Compared with placebo, apixaban (HR = 0.97, 95% CI: 0.88-1.07), rivaroxaban (HR = 0.91, 95% CI: 0.76-1.10), and warfarin (HR = 0.96, 95% CI: 0.90-1.01) did not reduce mortality. Regarding direct comparisons of mortality, the comparisons of warfarin vs. apixaban (HR = 0.99, 95% CI: 0.92-1.06), placebo vs. warfarin (HR = 1.04, 95% CI: 0.99-1.11), and rivaroxaban vs. warfarin (HR = 0.96, 95% CI: 0.80-1.14) did not significantly reduce mortality. Based on the surface under the cumulative ranking curve, rivaroxaban (75.53%), warfarin (62.14%), and apixaban (45.6%) were the most effective interventions for managing mortality, and placebo (16.74%) was the worst. In conclusion, rivaroxaban demonstrated efficacy in reducing mortality and the incidence of ischemic stroke, gastrointestinal bleeding, and intracranial hemorrhage. Dabigatran is recommended for the prevention of hemorrhagic stroke. However, caution should be exercised due to the risk of major bleeding. Warfarin can effectively reduce minor bleeding but does not offer significant protection against gastrointestinal or intracranial bleeding. Apixaban was not recommended for mortality reduction or for preventing ischemic or hemorrhagic strokes. Further research will be necessary to establish specific clinical protocols.
PubMed: 38161701
DOI: 10.3389/fphar.2023.1320939 -
Clinical Cardiology Jan 2021Although the European Medicines Agency and the US Food and Drug Administration have, respectively, approved rivaroxaban for the prevention of recurrent major adverse... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Although the European Medicines Agency and the US Food and Drug Administration have, respectively, approved rivaroxaban for the prevention of recurrent major adverse cardiovascular events in patients with myocardial infarction and stable coronary artery disease, its efficacy and safety is unclear. This meta-analysis aimed to evaluate the benefit and risk of adding rivaroxaban in coronary artery disease (CAD) patients, focusing on treatment effects stratified by different baseline clinical presentations.
HYPOTHESIS
There are differences in treatment effects of adding rivaroxaban among CAD patients with different baseline clinical presentations.
METHODS
Medline, EMBASE, and Cochrane Databases were systematically searched from inception to 21 July 2020 for randomized controlled trials (RCTs) comparing rivaroxaban in CAD patients. The primary efficacy endpoint and safety endpoint were assessed by using Mantel-Haenszel pooled risk ratios (RRs) and 95% confidence intervals (CIs).
RESULTS
Five RCTs that included 43 650 patients were identified. Patients receiving rivaroxaban had a significantly lower risk of the primary efficacy endpoint (RR, 0.86; 95% CI, 0.76-0.97, p = .01) accompanied by increased risk of the primary safety endpoint (RR, 1.83; 95% CI, 1.10-3.05, p = .02). Subgroup analyses showed that in males the risk-benefit appears to be more favorable while in patients ≥65 years, in females, in patients with diabetes, those with mild to moderate impaired renal function, and region of Asia/other seems unfavorable.
CONCLUSION
Rivaroxaban may provide an additional choice for secondary prevention in CAD patients. However, careful estimation of the risk of ischemic and bleeding events using patient characteristics are critical to achieving net benefit.
Topics: Coronary Artery Disease; Factor Xa Inhibitors; Hemorrhage; Humans; Risk Factors; Rivaroxaban
PubMed: 33219708
DOI: 10.1002/clc.23514 -
Journal of the American Heart... Apr 2024Concomitant atrial fibrillation and end-stage renal disease is common and associated with an unfavorable prognosis. Although oral anticoagulants have been well... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Concomitant atrial fibrillation and end-stage renal disease is common and associated with an unfavorable prognosis. Although oral anticoagulants have been well established to prevent thromboembolism, the applicability in patients under long-term dialysis remains debatable. The study aimed to determine the efficacy and safety of anticoagulation in the dialysis-dependent population.
METHODS AND RESULTS
An updated network meta-analysis based on MEDLINE, EMBASE, and the Cochrane Library was performed. Studies published up to December 2022 were included. Direct oral anticoagulants (DOACs, dabigatran, rivaroxaban, apixaban 2.5/5 mg twice daily), vitamin K antagonists (VKAs), and no anticoagulation were compared on safety and efficacy outcomes. The outcomes of interest were major bleeding, thromboembolism, and all-cause death. A total of 42 studies, including 3 randomized controlled trials, with 185 864 subjects were pooled. VKAs were associated with a significantly higher risk of major bleeding than either no anticoagulation (hazard ratio [HR], 1.47; 95% CI, 1.34-1.61) or DOACs (DOACs versus VKAs; HR, 0.74 [95% CI, 0.64-0.84]). For the prevention of thromboembolism, the efficacies of VKAs, DOACs, and no anticoagulation were equivalent. Nevertheless, dabigatran and rivaroxaban were associated with fewer embolic events. There were no differences in all-cause death with the administration of VKAs, DOACs, or no anticoagulation.
CONCLUSIONS
For dialysis-dependent populations, dabigatran and rivaroxaban were associated with better efficacy, while dabigatran and apixaban demonstrated better safety. No anticoagulation was a noninferior alterative, and VKAs were associated with the worst outcomes.
Topics: Humans; Atrial Fibrillation; Rivaroxaban; Dabigatran; Stroke; Network Meta-Analysis; Anticoagulants; Hemorrhage; Fibrinolytic Agents; Administration, Oral; Kidney Failure, Chronic; Thromboembolism; Randomized Controlled Trials as Topic
PubMed: 38606775
DOI: 10.1161/JAHA.123.034176 -
BMJ Open Jun 2014To examine the comparative efficacy and safety of antithrombotic treatments (apixaban, dabigatran, edoxaban, rivaroxaban and vitamin K antagonists (VKA) at a standard... (Comparative Study)
Comparative Study Meta-Analysis Review
OBJECTIVE
To examine the comparative efficacy and safety of antithrombotic treatments (apixaban, dabigatran, edoxaban, rivaroxaban and vitamin K antagonists (VKA) at a standard adjusted dose (target international normalised ratio 2.0-3.0), acetylsalicylic acid (ASA), ASA and clopidogrel) for non-valvular atrial fibrillation and among subpopulations.
DESIGN
Systematic review and network meta-analysis.
DATA SOURCES
A systematic literature search strategy was designed and carried out using MEDLINE, EMBASE, the Cochrane Register of Controlled Trials and the grey literature including the websites of regulatory agencies and health technology assessment organisations for trials published in English from 1988 to January 2014.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Randomised controlled trials were selected for inclusion if they were published in English, included at least one antithrombotic treatment and involved patients with non-valvular atrial fibrillation eligible to receive anticoagulant therapy.
RESULTS
For stroke or systemic embolism, dabigatran 150 mg and apixaban twice daily were associated with reductions relative to standard adjusted dose VKA, whereas low-dose ASA and the combination of clopidogrel plus low-dose ASA were associated with increases. Absolute risk reductions ranged from 6 fewer events per 1000 patients treated for dabigatran 150 mg twice daily to 15 more events for clopidogrel plus ASA. For major bleeding, edoxaban 30 mg daily, apixaban, edoxaban 60 mg daily and dabigatran 110 mg twice daily were associated with reductions compared to standard adjusted dose VKA. Absolute risk reductions with these agents ranged from 18 fewer per 1000 patients treated each year for edoxaban 30 mg daily to 24 more for medium dose ASA.
CONCLUSIONS
Compared with standard adjusted dose VKA, new oral anticoagulants were associated with modest reductions in the absolute risk of stroke and major bleeding. People on antiplatelet drugs experienced more strokes compared with anticoagulant drugs without any reduction in bleeding risk. To fully elucidate the comparative benefits and harms of antithrombotic agents across the various subpopulations, rigorously conducted comparative studies or network meta-regression analyses of patient-level data are required.
SYSTEMATIC REVIEW REGISTRATION NUMBER
PROSPERO registry-CRD42012002721.
Topics: Atrial Fibrillation; Fibrinolytic Agents; Hemorrhage; Humans; Randomized Controlled Trials as Topic; Severity of Illness Index; Stroke
PubMed: 24889848
DOI: 10.1136/bmjopen-2013-004301 -
Clinical and Applied... 2020There is no direct evidence comparing the 2 most commonly prescribed direct oral anticoagulants, apixaban and rivaroxaban, used for stroke prevention in nonvalvular... (Comparative Study)
Comparative Study
There is no direct evidence comparing the 2 most commonly prescribed direct oral anticoagulants, apixaban and rivaroxaban, used for stroke prevention in nonvalvular atrial fibrillation (NVAF). A number of network meta-analyses (NMAs) of randomized control trials and real-world evidence (RWE) studies comparing the efficacy, effectiveness, and safety of apixaban and rivaroxaban have been published; however, a comprehensive evidence review across the available body of evidence is lacking. In this study, we aimed to systematically review and evaluate the clinical outcomes of apixaban and rivaroxaban using a combination of data gleaned from both NMAs and RWE studies. The review identified 21 NMAs and 5 RWE studies. The data demonstrated that apixaban was associated with fewer major bleeding events compared to rivaroxaban. There was no difference in the efficacy/effectiveness profiles between these treatments. Bleeding is a serious complication of anticoagulation therapy for the management of NVAF, and is associated with increased rates of hospitalization, morbidity, mortality, and health-care expenditure. The majority of studies in this comprehensive evidence review suggests that apixaban has a lower risk of major bleeding events compared to rivaroxaban in patients with NVAF.
Topics: Aged; Atrial Fibrillation; Female; Hemorrhage; Humans; Male; Middle Aged; Network Meta-Analysis; Pyrazoles; Pyridones; Rivaroxaban
PubMed: 31918558
DOI: 10.1177/1076029619898764 -
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