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European Heart Journal. Cardiovascular... Apr 2021The aim of the present meta-analysis was to evaluate the efficacy and safety of non-vitamin K oral antagonists (NOACs) vs. vitamin K antagonists (VKAs) in elderly... (Meta-Analysis)
Meta-Analysis
Safety and efficacy of non-vitamin K antagonist oral anticoagulants in elderly patients with atrial fibrillation: systematic review and meta-analysis of 22 studies and 440 281 patients.
AIMS
The aim of the present meta-analysis was to evaluate the efficacy and safety of non-vitamin K oral antagonists (NOACs) vs. vitamin K antagonists (VKAs) in elderly patients with atrial fibrillation (AF) and indirectly compare NOACs in this population.
METHODS AND RESULTS
MEDLINE, Cochrane, ISI Web of Sciences, and SCOPUS were searched for randomized or adjusted observational studies comparing NOACs vs. VKAs for stroke prevention in AF patients ≥75 years. The primary efficacy and safety outcomes of this meta-analysis were the composite of stroke and systemic embolism (SSE) and major bleedings, respectively. Other secondary outcomes were also analysed. The analysis included 22 studies enrolling 440 281 AF patients ≥ 75 years. The risk of SSE was significantly lower with NOACs vs. VKAs [hazard ratio (HR) 0.79; 95% confidence interval (CI) 0.70-0.89], whereas no differences were found for major bleedings (HR 0.94; 95% CI 0.85-1.05). NOACs reduced the risk of intracranial bleeding (HR 0.46; 95% CI 0.38-0.58), haemorrhagic stroke (HR 0.61; 95% CI 0.48-0.79) and fatal bleeding (HR 0.46; 95% CI 0.30-0.72) but increased gastrointestinal (GI) bleedings (HR 1.46; 95% CI 1.30-1.65), compared to VKAs. The adjusted indirect comparison showed no significant differences in term of SSE between NOAC agents. Conversely, the risk of major bleeding was higher for rivaroxaban vs. apixaban (HR 1.69; 95% CI 1.39-2.08) and edoxaban (HR 1.37; 95% CI 1.14-1.67), and for dabigatran vs. apixaban (HR 1.47; 95% CI 1.18-1.85).
CONCLUSION
In elderly patients with AF, NOACs are associated to a lower risk of SSE, intracranial bleeding, haemorrhagic stroke and fatal bleeding than VKAs, but increase GI bleedings. In this analysis, the safety profile of individual NOAC agents was significantly different.
Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Gastrointestinal Hemorrhage; Humans; Vitamin K
PubMed: 31830264
DOI: 10.1093/ehjcvp/pvz073 -
Journal of Hematology & Oncology May 2022International clinical practice guidelines have progressively endorsed direct oral anticoagulants (DOACs) as an alternative to low-molecular-weight heparins (LMWHs)... (Meta-Analysis)
Meta-Analysis
Direct oral anticoagulant versus low molecular weight heparin for the treatment of cancer-associated venous thromboembolism: 2022 updated systematic review and meta-analysis of randomized controlled trials.
International clinical practice guidelines have progressively endorsed direct oral anticoagulants (DOACs) as an alternative to low-molecular-weight heparins (LMWHs) monotherapy for the initial and long-term treatment of cancer-associated thrombosis (CAT). Several new randomized controlled trials (RCTs) have recently reported additional results on the safety and efficacy of DOACs in this setting. We performed an updated meta-analysis of all publicly available data from RCTs comparing DOACs with LMWHs for the treatment of CAT. Six RCTs enrolling 3690 patients with CAT were included. Compared with LMWHs, DOACs significantly decreased the risk of CAT recurrence (RR, 0.67; 95%CI, 0.52-0.85), with a non-significant increase in the risk of major bleeding (RR, 1.17; 95%CI, 0.82-1.67), a significant increase in the risk of clinically relevant nonmajor bleeding (RR 1.66; 95%CI, 1.31-2.09) and no difference in all-cause mortality rates. These results increase the level of certainty of available evidence supporting the use of DOACs as an effective and safe option for the treatment of CAT in selected cancer patients.
Topics: Anticoagulants; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Randomized Controlled Trials as Topic; Thrombosis; Venous Thromboembolism
PubMed: 35598026
DOI: 10.1186/s13045-022-01289-1 -
The Annals of Pharmacotherapy Jun 2021To evaluate how treatment with DOACs for VTE affects thrombosis and bleeding outcomes compared to warfarin in CKD and dialysis patients.
OBJECTIVE
To evaluate how treatment with DOACs for VTE affects thrombosis and bleeding outcomes compared to warfarin in CKD and dialysis patients.
DATA SOURCES
A literature search was conducted for studies evaluating VTE and bleeding outcomes with DOAC use in CKD and dialysis patients. Searches conducted through EMBASE, MEDLINE/PubMed, Scopus, and Cochrane Central Register of Controlled Trials, from inception to September 22, 2020.
STUDY SELECTION AND DATA EXTRACTION
Randomized controlled trials, cohort studies, and case series with ≥10 patients included.
DATA SYNTHESIS
From 7286 studies, nine studies met inclusion criteria. There was no significant difference between DOACs (dabigatran, rivaroxaban, apixaban) and warfarin for reducing recurrent VTE and bleeding events in moderate CKD patients. The risk of overall major bleeding increased when the degree of kidney impairment increased. There was no significant difference between apixaban and warfarin for VTE outcomes in dialysis patients.
RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE
There continues to be a controversial debate whether it may be more beneficial to use DOACs versus warfarin in CKD/dialysis patients with venous thromboembolism (VTE). The risk vs benefit of using DOACs in the CKD/ESKD population should continue to be evaluated for each individual patient.
CONCLUSION
Apixaban may be used cautiously as an alternative in acute VTE treatment in severe CKD patients. Insufficient evidence is available to suggest the use of dabigatran and rivaroxaban in this patient population. The benefit of using DOACs in this population for VTE treatment should be weighed against the potential bleeding risk in patients with CKD.
Topics: Administration, Oral; Anticoagulants; Hemorrhage; Humans; Renal Dialysis; Renal Insufficiency, Chronic; Rivaroxaban; Thrombosis; Venous Thromboembolism
PubMed: 33073581
DOI: 10.1177/1060028020967635 -
European Journal of Neurology Oct 2018Intracranial hemorrhage (ICH) is the most feared complication in patients treated with oral anticoagulants due to non-valvular atrial fibrillation. Non-vitamin K oral... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND PURPOSE
Intracranial hemorrhage (ICH) is the most feared complication in patients treated with oral anticoagulants due to non-valvular atrial fibrillation. Non-vitamin K oral anticoagulants (NOACs) reduce the risk of ICH compared with vitamin K antagonists (VKAs). We performed a systematic review and meta-analysis to evaluate the risk of fatal NOAC-related ICH compared with VKA-related ICH.
METHODS
We calculated the corresponding risk ratios (RRs) in each included study to express the relative risk of fatal ICH amongst all patients receiving oral anticoagulation with either NOACs or VKAs. We additionally evaluated the mortality rates in NOAC-related ICH in patients treated with and without NOAC-specific reversal agents (idarucizumab and factor Xa inhibitors antidote). Case fatality was evaluated at 30-90 days following symptom onset.
RESULTS
Our literature search identified six eligible studies (four randomized controlled trials and two open-label trials of NOAC-specific reversal agents). In pairwise analyses, NOACs were found to have a lower risk of fatal ICH compared with VKAs [RR, 0.46; 95% confidence interval (CI), 0.36-0.58] with no heterogeneity (I = 0%) across included randomized controlled trials. However, the case fatality rate was similar in NOAC-related and VKA-related (RR, 1.00; 95% CI, 0.84-1.19) ICH with no evidence of heterogeneity (I = 0%). In the indirect analysis, the case fatality rate of NOAC-related ICH in patients treated with specific reversal agents was lower compared with the remainder of the patients [17% (95% CI, 11-24%) vs. 41% (95% CI, 34-49%); P < 0.001].
CONCLUSIONS
Non-vitamin K oral anticoagulants halve the risk of fatal ICH in patients with non-valvular atrial fibrillation compared with VKAs, whereas indirect comparisons indicate that NOAC-specific reversal agents may be associated with a lower case fatality rate in NOAC-related ICH.
Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Intracranial Hemorrhages; Risk
PubMed: 29953696
DOI: 10.1111/ene.13742 -
Journal of Neurology Mar 2015The new oral anticoagulants/non-vitamin K antagonists oral anticoagulants (NOACs) have recently reached the market and less is known about their safety in comparison to... (Meta-Analysis)
Meta-Analysis Review
The new oral anticoagulants/non-vitamin K antagonists oral anticoagulants (NOACs) have recently reached the market and less is known about their safety in comparison to their efficacy. Therefore, we aimed to evaluate intracranial hemorrhage (ICH) risk with NOACs, the most feared adverse event of anticoagulation treatment. This is a systematic review and meta-analysis of phase III randomized controlled trials (RCTs) comparing NOACs versus any control and reporting ICH events. Studies were searched through Medline and Cochrane Library (April 2014). Reviews and reference lists were also screened. Random effects' meta-analysis was performed to derive pooled estimates expressed as relative risk (RR) and 95 % CI. Number needed to treat/harm (NNT/NNH) taking into account the baseline risk was also calculated. Heterogeneity was evaluated with I (2) test. 18 RCTs evaluating 148,149 patients were included. NOAC significantly reduced ICH risk compared to vitamin K antagonists (VKA) (RR 0.44; 95 % CI 0.36-0.54; I (2) = 37 %; NNT: 137 during 2 years) and to sequential treatment with low molecular weight heparin and VKA (RR 0.28; 95 % CI 0.12-0.65; I (2) = 0 %; NNT: 463 patients during 7 months). Compared to placebo, NOACs were associated with an increased ICH risk (RR 3.31; 95 % CI 1.59-6.90; I (2) = 0 %; NNH: 433 during 1 year). Results were similar for the different NOAC drugs and across the different clinical conditions. In patients requiring anticoagulation treatment, the risk of ICH is about half with the NOACs in comparison to standard antithrombotic treatment. This safer profile found in RCTs should be confirmed in real-world database studies.
Topics: Administration, Oral; Anticoagulants; Humans; Intracranial Hemorrhages; Randomized Controlled Trials as Topic; Risk
PubMed: 25119841
DOI: 10.1007/s00415-014-7462-0 -
BioMed Research International 2017NaoXueShu oral liquid invigorates Qi and promotes blood circulation, which is mainly used for treating the acute stage of the meridian of hemorrhagic apoplexy and acute... (Meta-Analysis)
Meta-Analysis Review
NaoXueShu oral liquid invigorates Qi and promotes blood circulation, which is mainly used for treating the acute stage of the meridian of hemorrhagic apoplexy and acute blood stasis syndrome during early convalescence. Its main clinical manifestations include hemiplegia, mouth askew, hemianesthesia, and inarticulateness. It is used mainly in patients with lobar hemorrhage, basal ganglia, and thalamus of the small amount of bleeding without disturbing consciousness of hypertensive cerebral. The purpose of this study was to evaluate the efficacy and adverse effects of NaoXueShu oral liquid on the treatment of cerebral hemorrhage. In this study, literature on randomized controlled trials was collected from seven databases to evaluate the clinical efficiency of the treatment of cerebral hemorrhage alone or combined with Western medicine. The methodologic quality of the included studies was assessed using a standard Cochrane system review and analyzed using RevMan 5.3.0 software. The study included 14 eligible randomized controlled trials. The results showed that the use of NaoXueShu oral liquid alone or combined with other drugs or auxiliary methods can play a significant role in the treatment of cerebral hemorrhage, especially hypertensive intracerebral hemorrhage.
Topics: Administration, Oral; Cerebral Hemorrhage; Female; Humans; Male; Plant Preparations
PubMed: 28630871
DOI: 10.1155/2017/8542576 -
Journal of Medical Internet Research Jul 2023Oral anticoagulation is the cornerstone treatment of several diseases. Its management is often challenging, and different telemedicine strategies have been implemented... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Oral anticoagulation is the cornerstone treatment of several diseases. Its management is often challenging, and different telemedicine strategies have been implemented to support it.
OBJECTIVE
The aim of the study is to systematically review the evidence on the impact of telemedicine-based oral anticoagulation management compared to usual care on thromboembolic and bleeding events.
METHODS
Randomized controlled trials were searched in 5 databases from inception to September 2021. Two independent reviewers performed study selection and data extraction. Total thromboembolic events, major bleeding, mortality, and time in therapeutic range were assessed. Results were pooled using random effect models.
RESULTS
In total, 25 randomized controlled trials were included (n=25,746 patients) and classified as moderate to high risk of bias by the Cochrane tool. Telemedicine resulted in lower rates of thromboembolic events, though not statistically significant (n=13 studies, relative risk [RR] 0.75, 95% CI 0.53-1.07; I=42%), comparable rates of major bleeding (n=11 studies, RR 0.94, 95% CI 0.82-1.07; I=0%) and mortality (n=12 studies, RR 0.96, 95% CI 0.78-1.20; I=11%), and an improved time in therapeutic range (n=16 studies, mean difference 3.38, 95% CI 1.12-5.65; I=90%). In the subgroup of the multitasking intervention, telemedicine resulted in an important reduction of thromboembolic events (RR 0.20, 95% CI 0.08-0.48).
CONCLUSIONS
Telemedicine-based oral anticoagulation management resulted in similar rates of major bleeding and mortality, a trend for fewer thromboembolic events, and better anticoagulation quality compared to standard care. Given the potential benefits of telemedicine-based care, such as greater access to remote populations or people with ambulatory restrictions, these findings may encourage further implementation of eHealth strategies for anticoagulation management, particularly as part of multifaceted interventions for integrated care of chronic diseases. Meanwhile, researchers should develop higher-quality evidence focusing on hard clinical outcomes, cost-effectiveness, and quality of life.
TRIAL REGISTRATION
PROSPERO International Prospective Register of Systematic Reviews CRD42020159208; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=159208.
Topics: Humans; Anticoagulants; Quality of Life; Hemorrhage; Thromboembolism; Telemedicine
PubMed: 37428532
DOI: 10.2196/45922 -
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 -
Journal of Neurology Feb 2022We performed a systematic review and meta-analysis to compare the risk of intracranial hemorrhage (ICH) between direct oral anticoagulants (DOACs) and other... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
We performed a systematic review and meta-analysis to compare the risk of intracranial hemorrhage (ICH) between direct oral anticoagulants (DOACs) and other antithrombotic drugs in detail across all diseases.
METHODS
PubMed, EMBASE, Web of Science, and the Cochrane Library were searched for relevant randomized controlled trials (RCTs). Heterogeneity was examined using the I statistic. Risk ratio (RR) and 95% confidence interval (CI) were calculated using random-effects meta-analysis.
RESULTS
Fifty-five RCTs were included in this meta-analysis. Compared with vitamin K antagonists (VKAs), dabigatran reduced the risk of ICH by 60% (RR 0.40; 95% CI 0.28-0.57), apixaban by 57% (RR 0.43; 95% CI 0.31-0.58), edoxaban by 56% (RR 0.44; 95% CI 0.29-0.67) and rivaroxaban by 41% (RR 0.59; 95%CI 0.44-0.80). Compared with low-molecular-weight heparins (LMWHs), apixaban, edoxaban and rivaroxaban had a similar risk of ICH. Compared with aspirin, dabigatran and apixaban had a similar risk of ICH, while rivaroxaban posed an increased risk of ICH (RR 2.12; 95% CI 1.31-3.44). For secondary prevention stroke, DOACs reduced the risk of ICH by 46% compared with warfarin (RR 0.54; 95% CI [0.42-0.70]) and had a similar risk of ICH compared with aspirin.
CONCLUSION
All DOACs had a lower risk of ICH than VKAs. In terms of the risk of ICH, DOACs were overall as safe as LMWHs, and apixaban and dabigatran were as safe as aspirin, but rivaroxaban was not. For secondary prevention stroke, the risk of ICH with DOACs was overall lower than warfarin and similar to aspirin, but it should be noted that compared with aspirin, rivaroxaban may increase the risk of ICH. This is the first pair-wise meta-analysis that compares the risk of ICH between DOACs and other antithrombotic drugs in detail across all diseases, which may have certain significance for patients with high risk of ICH to choose antithrombotic drugs in clinical practice.
Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Dabigatran; Humans; Intracranial Hemorrhages; Randomized Controlled Trials as Topic; Stroke
PubMed: 33594452
DOI: 10.1007/s00415-021-10448-2 -
Healthcare (Basel, Switzerland) Dec 2022Dental procedures have posed challenges in managing anticoagulated patients due to early reports of oral hemorrhage. This study aims to evaluate the risks of... (Review)
Review
Dental procedures have posed challenges in managing anticoagulated patients due to early reports of oral hemorrhage. This study aims to evaluate the risks of postoperative bleeding with the local application of tranexamic acid. A systematic search was conducted until 31 March 2022, with keywords including tranexamic acid, oral hemorrhage, dental, and/or coagulation. The following databases were searched: PubMed, Scopus, Web of Science, CINAHL Plus, and Cochrane Library. Statistical analysis was conducted using Review Manager 5.4. In total, 430 patients were pooled in with the local application of tranexamic acid using mouthwash, irrigation, and compression with a gauze/gauze pad. The mean age was 61.8 years in the intervention group and 58.7 in the control group. Only 4 patients in the intervened group out of the 210 discontinued the trial due to non-drug-related adverse events. The risk difference was computed as -0.07 ( = 0.05), meaning that patients administered with local antifibrinolytic therapy for postoperative bleeding reduction for dental procedures were at a 7% less risk of oral bleeding. Current evidence on managing anticoagulated patients undergoing dental or oral procedures remains unclear. The present study presents favorable outcomes of postoperative bleeding with local tranexamic acid used in the postoperative period.
PubMed: 36554047
DOI: 10.3390/healthcare10122523