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Thrombosis and Haemostasis Nov 2023Direct oral anticoagulants (DOACs) are effective for the management of thromboembolic disorders. However, bleeding remains a major concern in cirrhotic patients... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Direct oral anticoagulants (DOACs) are effective for the management of thromboembolic disorders. However, bleeding remains a major concern in cirrhotic patients receiving DOACs.
METHODS
PubMed, EMBASE, and Cochrane Library databases were searched. The incidence of bleeding episodes in cirrhotic patients receiving DOACs was pooled. Odds ratios (ORs) were calculated to compare the incidence of bleeding episodes in cirrhotic patients who received DOACs versus those who received conventional anticoagulants and did not receive anticoagulants.
RESULTS
Twenty-nine studies were included. All bleeding, major bleeding, fatal bleeding, gastrointestinal bleeding, and intracranial hemorrhage episodes were observed in 310/2,469, 100/1,388, 2/611, 166/1,886, and 5/1,147 cirrhotic patients receiving DOACs, respectively. Their pooled incidences were 13, 6, 0, 8, and 0%, respectively. They became higher in subgroup analyses of studies with advanced age, a longer treatment duration, and Child-Turcotte-Pugh class C. Compared with conventional anticoagulants, DOACs were associated with lower incidences of all bleeding (OR = 0.71, 95% confidence interval [CI] = 0.52-0.98) and major bleeding (OR = 0.55, 95% CI = 0.37-0.83) in cirrhotic patients, but not those of fatal bleeding (OR = 0.21, 95% CI = 0.04-1.28), gastrointestinal bleeding (OR = 0.78, 95% CI = 0.52-1.17), or intracranial hemorrhage (OR = 0.36, 95% CI = 0.12-1.12). The incidences of all bleeding (OR = 1.04, 95% CI = 0.22-4.79) and major bleeding (OR = 0.96, 95% CI = 0.26-3.61) did not significantly differ between cirrhotic patients with portal vein thrombosis (PVT) who received DOACs and those who did not receive anticoagulants.
CONCLUSION
DOACs carry a low risk of bleeding in liver cirrhosis. Age, treatment duration, and Child-Turcotte-Pugh class may be associated with bleeding in cirrhotic patients receiving DOACs. The risk of bleeding is not increased by DOACs in cirrhotic patients with PVT.
Topics: Humans; Anticoagulants; Gastrointestinal Hemorrhage; Venous Thrombosis; Liver Cirrhosis; Venous Thromboembolism; Intracranial Hemorrhages; Administration, Oral
PubMed: 37336474
DOI: 10.1055/s-0043-1770100 -
The American Journal of Cardiology Oct 2023Pivotal trials comparing direct oral anticoagulants (DOACs) against warfarin in patients with atrial fibrillation (AF) predominantly involved patients with high stroke... (Meta-Analysis)
Meta-Analysis
Pivotal trials comparing direct oral anticoagulants (DOACs) against warfarin in patients with atrial fibrillation (AF) predominantly involved patients with high stroke risk. This study aimed to evaluate the efficacy and safety of DOAC versus warfarin in patients with low stroke risk. An online literature search was conducted to retrieve studies comparing clinical outcomes between patients treated with DOAC versus warfarin for AF, reporting outcomes for patients at low or minimal risk of stroke (CHADS-VASc scores ranging from 0 to 2 or CHADS scores ranging from 0 to 1). The primary outcome was the occurrence of stroke or systemic embolism. Secondary outcomes included major bleeding, intracranial hemorrhage, and all-cause mortality. Hazard ratios for all outcomes were pooled in random-effects meta-analyses. A network meta-analysis of individual DOACs versus warfarin was also conducted. In total, 11 studies (132,980 patients) were included. DOAC was associated with a significantly lower risk of stroke or systemic embolism (hazard ratio 0.85, 95% confidence interval 0.75 to 0.96, p = 0.008, I = 0%), major bleeding, intracranial hemorrhage, and mortality compared with warfarin. This benefit persisted even when study arms which had CHADS-VASc scores of 2 were excluded. When restricted to 3 studies investigating only patients with a single nongender-related stroke risk factor, significant benefit was seen only for the outcome of major bleeding. In the network meta-analysis, only dabigatran was superior to warfarin for all 4 outcomes. In conclusion, DOACs should be the standard of care in low-risk patients with AF who require anticoagulation. In particular, dabigatran appears to have the best balance of stroke prevention and reduction in major bleeding.
Topics: Humans; Warfarin; Atrial Fibrillation; Dabigatran; Anticoagulants; Treatment Outcome; Stroke; Hemorrhage; Intracranial Hemorrhages; Embolism; Risk Factors; Administration, Oral
PubMed: 37573616
DOI: 10.1016/j.amjcard.2023.07.108 -
Lancet (London, England) Jan 2012Uptake of self-testing and self-management of oral anticoagulation [corrected] has remained inconsistent, despite good evidence of their effectiveness. To clarify the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Uptake of self-testing and self-management of oral anticoagulation [corrected] has remained inconsistent, despite good evidence of their effectiveness. To clarify the value of self-monitoring of oral anticoagulation, we did a meta-analysis of individual patient data addressing several important gaps in the evidence, including an estimate of the effect on time to death, first major haemorrhage, and thromboembolism.
METHODS
We searched Ovid versions of Embase (1980-2009) and Medline (1966-2009), limiting searches to randomised trials with a maximally sensitive strategy. We approached all authors of included trials and requested individual patient data: primary outcomes were time to death, first major haemorrhage, and first thromboembolic event. We did prespecified subgroup analyses according to age, type of control-group care (anticoagulation-clinic care vs primary care), self-testing alone versus self-management, and sex. We analysed patients with mechanical heart valves or atrial fibrillation separately. We used a random-effect model method to calculate pooled hazard ratios and did tests for interaction and heterogeneity, and calculated a time-specific number needed to treat.
FINDINGS
Of 1357 abstracts, we included 11 trials with data for 6417 participants and 12,800 person-years of follow-up. We reported a significant reduction in thromboembolic events in the self-monitoring group (hazard ratio 0·51; 95% CI 0·31-0·85) but not for major haemorrhagic events (0·88, 0·74-1·06) or death (0·82, 0·62-1·09). Participants younger than 55 years showed a striking reduction in thrombotic events (hazard ratio 0·33, 95% CI 0·17-0·66), as did participants with mechanical heart valve (0·52, 0·35-0·77). Analysis of major outcomes in the very elderly (age ≥85 years, n=99) showed no significant adverse effects of the intervention for all outcomes.
INTERPRETATION
Our analysis showed that self-monitoring and self-management of oral coagulation is a safe option for suitable patients of all ages. Patients should also be offered the option to self-manage their disease with suitable health-care support as back-up.
FUNDING
UK National Institute for Health Research (NIHR) Technology Assessment Programme, UK NIHR National School for Primary Care Research.
Topics: Administration, Oral; Anticoagulants; Drug Monitoring; Hemorrhage; Humans; International Normalized Ratio; Self Care; Thromboembolism; Vitamin K
PubMed: 22137798
DOI: 10.1016/S0140-6736(11)61294-4 -
European Journal of Internal Medicine Jan 2024The prevalence of atrial fibrillation (AF) in individuals with end-stage renal disease (ESRD) on chronic hemodialysis is increasing. The optimal anticoagulant choice in... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of direct oral anticoagulants vs vitamin K antagonists in patients with atrial fibrillation and end-stage renal disease on hemodialysis: A systematic review and meta-analysis.
BACKGROUND
The prevalence of atrial fibrillation (AF) in individuals with end-stage renal disease (ESRD) on chronic hemodialysis is increasing. The optimal anticoagulant choice in this population is unclear since these patients were excluded from the pivotal randomized controlled trials (RCTs) of direct oral anticoagulants (DOACs) vs. vitamin K antagonists (VKAs) in the general AF population. We aimed to assess the efficacy and safety of DOACs vs. VKAs in patients with AF and ESRD on chronic hemodialysis through a systematic review and meta-analysis of all available evidence.
PATIENTS/METHODS
We performed a systematic search in MEDLINE and Scopus for RCTs or observational studies of patients with AF and ESRD on chronic hemodialysis who were treated with DOACs or VKAs. The outcomes of interest included ischemic stroke, the composite of ischemic stroke or systemic embolism, major bleeding, gastrointestinal bleeding, minor bleeding events and all-cause mortality.
RESULTS
Among 397 studies identified from the literature search, six studies (three RCTs and three observational studies) were included in the meta-analysis. Compared with VKA-treated patients, those treated with DOACs had similar risk of ischemic stroke (RR:0.76, 95% CI:0.41-1.41), ischemic stroke or systemic embolism (RR:0.65, 95% CI:0.38-1.10), major bleeding (RR:0.79, 95% CI:0.49-1.28) and all-cause death (RR:0.79, 95% CI:0.56-1.12). The risk of gastrointestinal bleeding was lower in DOAC- vs VKA-treated patients in three eligible observational studies (RR:0.73, 95% CI: 0.54-0.99, I2 = 79%) but this was not confirmed in two eligible RCTs (RR:0.69, 95% CI: 0.33-1.43, I2 = 0%).
CONCLUSIONS
Among AF patients with ESRD on chronic hemodialysis, the risk of ischemic stroke, ischemic stroke or systemic embolism, minor bleeding, major bleeding, and all-cause mortality is similar in patients treated with DOACs compared to VKAs. Given that the meta-analysis of RCTs on gastrointestinal bleeding did not confirm the results of the meta-analysis of the observational studies, it cannot be concluded that gastrointestinal bleeding is lower among DOAC-treated patients.
PROTOCOL REGISTRATION
PROSPERO CRD42023391966.
Topics: Humans; Administration, Oral; Anticoagulants; Atrial Fibrillation; Embolism; Gastrointestinal Hemorrhage; Ischemic Stroke; Kidney Failure, Chronic; Randomized Controlled Trials as Topic; Renal Dialysis; Stroke; Vitamin K
PubMed: 37648582
DOI: 10.1016/j.ejim.2023.08.020 -
Journal of the American College of... Jun 2021Direct oral anticoagulants (DOACs) have shown a positive benefit-risk balance in both clinical trials and real-world data, but approximately 2% to 3.5% of patients... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Direct oral anticoagulants (DOACs) have shown a positive benefit-risk balance in both clinical trials and real-world data, but approximately 2% to 3.5% of patients experience major bleeding annually. Many of these patients require hospitalization, and the administration of reversal agents may be required to control bleeding.
OBJECTIVES
The aim of this study was to investigate clinical outcomes associated with the use of 4-factor prothrombin complex concentrates, idarucizumab, or andexanet for reversal of severe DOAC-associated bleeding.
METHODS
The investigators systematically searched for studies of reversal agents for the treatment of severe bleeding associated with DOAC. Mortality rates, thromboembolic events, and hemostatic efficacy were meta-analyzed using a random effects model.
RESULTS
The investigators evaluated 60 studies in 4,735 patients with severe DOAC-related bleeding who were treated with 4-factor prothrombin complex concentrates (n = 2,688), idarucizumab (n = 1,111), or andexanet (n = 936). The mortality rate was 17.7% (95% confidence interval [CI]: 15.1% to 20.4%), and it was higher in patients with intracranial bleedings (20.2%) than in patients with extracranial hemorrhages (15.4%). The thromboembolism rate was 4.6% (95% CI: 3.3% to 6.0%), being particularly high with andexanet (10.7%; 95% CI: 6.5% to 15.7%). The effective hemostasis rate was 78.5% (95% CI: 75.1% to 81.8%) and was similar regardless of the reversal agent considered. The rebleeding rate was 13.2% (95% CI: 5.5% to 23.1%) and 78% of rebleeds occurred after resumption of anticoagulation. The risk of death was markedly and significantly associated with failure to achieve effective hemostasis (relative risk: 3.63; 95% CI: 2.56 to 5.16). The results were robust regardless of the type of study or the hemostatic scale used.
CONCLUSIONS
The risk of death after severe DOAC-related bleeding remains significant despite a high rate of effective hemostasis with reversal agents. Failure to achieve effective hemostasis strongly correlated with a fatal outcome. Thromboembolism rates are particularly high with andexanet. Comparative clinical trials are needed.
Topics: Administration, Oral; Antibodies, Monoclonal, Humanized; Anticoagulants; Blood Coagulation; Blood Coagulation Factors; Factor Xa; Hemorrhage; Hemostasis; Humans; Recombinant Proteins; Retrospective Studies
PubMed: 34140101
DOI: 10.1016/j.jacc.2021.04.061 -
Thrombosis and Haemostasis Jan 2022The consensus of the Asia Pacific Heart Rhythm Society (APHRS) on stroke prevention in atrial fibrillation (AF) has been published in 2017 which provided useful clinical... (Meta-Analysis)
Meta-Analysis
The consensus of the Asia Pacific Heart Rhythm Society (APHRS) on stroke prevention in atrial fibrillation (AF) has been published in 2017 which provided useful clinical guidance for cardiologists, neurologists, geriatricians, and general practitioners in the Asia-Pacific region. In these years, many important new data regarding stroke prevention in AF were reported. The practice guidelines subcommittee members comprehensively reviewed updated information on stroke prevention in AF, and summarized them in this 2021 focused update of the 2017 consensus guidelines of the APHRS on stroke prevention in AF. We highlighted and focused on several issues, including the importance of the AF Better Care pathway, the advantages of non-vitamin K antagonist oral anticoagulants (NOACs) for Asians, the considerations of use of NOACs for Asian AF patients with single one stroke risk factor beyond gender, the role of lifestyle factors on stroke risk, the use of oral anticoagulants during the "coronavirus disease 2019" pandemic, etc. We fully realize that there are gaps, unaddressed questions, and many areas of uncertainty and debate in the current knowledge of AF, and the physician's decision remains the most important factor in the management of AF.
Topics: Acute Coronary Syndrome; Administration, Oral; Anticoagulants; Asia; Atrial Fibrillation; COVID-19; Catheter Ablation; Female; Heart Disease Risk Factors; Hemorrhage; Holistic Health; Humans; Male; Pandemics; Percutaneous Coronary Intervention; Risk Assessment; SARS-CoV-2; Societies, Medical; Stroke
PubMed: 34773920
DOI: 10.1055/s-0041-1739411 -
Journal of Zhejiang University.... Jul 2017Antithrombotic therapy using new oral anticoagulants (NOACs) in patients with atrial fibrillation (AF) has been generally shown to have a favorable risk-benefit profile.... (Meta-Analysis)
Meta-Analysis Review
Risk analysis of new oral anticoagulants for gastrointestinal bleeding and intracranial hemorrhage in atrial fibrillation patients: a systematic review and network meta-analysis.
BACKGROUND
Antithrombotic therapy using new oral anticoagulants (NOACs) in patients with atrial fibrillation (AF) has been generally shown to have a favorable risk-benefit profile. Since there has been dispute about the risks of gastrointestinal bleeding (GIB) and intracranial hemorrhage (ICH), we sought to conduct a systematic review and network meta-analysis using Bayesian inference to analyze the risks of GIB and ICH in AF patients taking NOACs.
METHODS
We analyzed data from 20 randomized controlled trials of 91 671 AF patients receiving anticoagulants, antiplatelet drugs, or placebo. Bayesian network meta-analysis of two different evidence networks was performed using a binomial likelihood model, based on a network in which different agents (and doses) were treated as separate nodes. Odds ratios (ORs) and 95% confidence intervals (CIs) were modeled using Markov chain Monte Carlo methods.
RESULTS
Indirect comparisons with the Bayesian model confirmed that aspirin+clopidogrel significantly increased the risk of GIB in AF patients compared to the placebo (OR 0.33, 95% CI 0.01-0.92). Warfarin was identified as greatly increasing the risk of ICH compared to edoxaban 30 mg (OR 3.42, 95% CI 1.22-7.24) and dabigatran 110 mg (OR 3.56, 95% CI 1.10-8.45). We further ranked the NOACs for the lowest risk of GIB (apixaban 5 mg) and ICH (apixaban 5 mg, dabigatran 110 mg, and edoxaban 30 mg).
CONCLUSIONS
Bayesian network meta-analysis of treatment of non-valvular AF patients with anticoagulants suggested that NOACs do not increase risks of GIB and/or ICH, compared to each other.
Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Bayes Theorem; Clinical Trials as Topic; Dabigatran; Female; Gastrointestinal Hemorrhage; Hemorrhage; Humans; Intracranial Hemorrhages; Male; Markov Chains; Middle Aged; Monte Carlo Method; Network Meta-Analysis; Odds Ratio; Pyridines; Randomized Controlled Trials as Topic; Risk; Thiazoles; Warfarin
PubMed: 28681581
DOI: 10.1631/jzus.B1600143 -
Cardiovascular Drugs and Therapy Apr 2023We aimed to determine the safety of direct oral anticoagulants (DOACs) for stroke prevention and treatment in patients with atrial fibrillation (AF). (Meta-Analysis)
Meta-Analysis Review
Severe Bleeding Risk of Direct Oral Anticoagulants Versus Vitamin K Antagonists for Stroke Prevention and Treatment in Patients with Atrial Fibrillation: A Systematic Review and Network Meta-Analysis.
PURPOSE
We aimed to determine the safety of direct oral anticoagulants (DOACs) for stroke prevention and treatment in patients with atrial fibrillation (AF).
METHODS
A systematic search of four databases (PubMed, EMBASE, Web of Science, and Cochrane Library) was performed to identify randomized controlled trials (RCTs) reporting severe bleeding events in patients taking DOACs or vitamin K antagonists (VKAs). In this frequency-based network meta-analysis, odds ratios and 95% confidence intervals were used for reporting. Based on the surface under the cumulative ranking curves (SUCRA), the relative ranking probability of each group was generated.
RESULTS
Twenty-three RCTs met the inclusion criteria, and a total of 87,616 patients were enrolled. The bleeding safety of DOACs for stroke prevention and treatment in patients with AF was ranked from highest to lowest as follows: fatal bleeding: edoxaban (SUCRA,80.2), rivaroxaban (SUCRA,68.3), apixaban (SUCRA,48.5), dabigatran (SUCRA,40.0), VKAs (SUCRA,12.9); major bleeding: dabigatran (SUCRA,74.0), apixaban (SUCRA,71.5), edoxaban (SUCRA,66.5), rivaroxaban (SUCRA,22.7), VKAs (SUCRA,15.4); gastrointestinal bleeding: apixaban (SUCRA,55.9), VKAs (SUCRA,53.7), edoxaban (SUCRA,50.5), rivaroxaban (SUCRA,50.4), dabigatran (SUCRA,39.5); intracranial hemorrhage: dabigatran (SUCRA,84.6), edoxaban (SUCRA,74.1), apixaban (SUCRA,65.8), rivaroxaban (SUCRA,24.4), VKAs (SUCRA,1.1).
CONCLUSION
Based on current evidence, for stroke prevention and treatment in patients with AF, the most safe DOAC is edoxaban in terms of fatal bleeding; dabigatran in terms of major bleeding and intracranial hemorrhage and apixaban in terms of gastrointestinal bleeding. However, given the nature of indirect comparisons, more high-quality evidence from head-to-head comparisons is still needed to confirm them.
Topics: Humans; Anticoagulants; Atrial Fibrillation; Dabigatran; Gastrointestinal Hemorrhage; Intracranial Hemorrhages; Network Meta-Analysis; Rivaroxaban; Stroke; Vitamin K; Factor Xa Inhibitors; Administration, Oral
PubMed: 34436708
DOI: 10.1007/s10557-021-07232-9 -
Cellular Physiology and Biochemistry :... 2016Upper gastrointestinal hemorrhage (UGH) is a serious medical condition which affects a large number of individuals. Endoscopic therapy accompanied by medication is a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND/AIMS
Upper gastrointestinal hemorrhage (UGH) is a serious medical condition which affects a large number of individuals. Endoscopic therapy accompanied by medication is a standard approach that is used to improve the prognosis of UGH patients and a few medications have been developed including proton pump inhibitors (PPIs), histamine H2 receptor antagonist (H2RA), somatostatin analogues and tranexamic acid. This study is set to compare the efficacy and safety of various medical interventions that are used to manage upper gastrointestinal bleeding.
METHODS
We searched PubMed, Cochrane Library, and Embase for relevant articles. Eligible studies were determined by using both the inclusion and exclusion criteria. Both traditional pair-wise meta-analysis and net-work analysis were carried out to evaluate the corresponding interventions.
RESULTS AND CONCLUSION
PPI is an effective medication for UGH patients and intravenous PPI exhibits equivalent effectiveness and safety in comparison to oral PPI. H2RA is not recommended for UGH patients as patients treated with H2RA are associated with an increased risk of adverse events including rebleeding, need for surgery and all-cause mortality. Moreover, patients treated with H2RA exhibit an increased length of average hospital stay and blood transfusion amount compared to those treated with PPI. Tranexamic acid is also considered as another promising medication for UGH.
Topics: Blood Transfusion; Gastrointestinal Hemorrhage; Histamine H2 Antagonists; Hospitalization; Humans; Proton Pump Inhibitors; Treatment Outcome
PubMed: 27855401
DOI: 10.1159/000452515 -
International Journal of Cardiology Oct 2022Several patients undergoing transcatheter aortic valve replacement (TAVR) also require oral anticoagulation (OAC) for atrial fibrillation (AF) or deep vein... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Several patients undergoing transcatheter aortic valve replacement (TAVR) also require oral anticoagulation (OAC) for atrial fibrillation (AF) or deep vein thromboembolism. However, the optimal type of OAC strategy (direct oral anticoagulants, DOACs, or vitamin K antagonists, VKA) is still unclear in this setting.
METHOD
We performed systematic literature research and meta-analysis in PubMed, Medline, and EMBASE databases for studies reporting either all-cause mortality, major/life-threatening bleeding or stroke events.
RESULTS
Ten observational studies and two randomized controlled trials (RCTs) including a total of 29,485 patients were eligible for inclusion. Compared to VKA, DOACs use after TAVR was associated with a modest but significantly lower rates of all-cause mortality (RR 0.90; 95% CI: 0.81-0.99, p-value 0.04) with results mainly driven by observational studies. Cardiovascular mortality (RR 1.03; 95% CI: 0.81-1.30; p-value 0.84), total stroke events (RR 0.97; 95% CI: 0.76-1.23, p-value 0.79), major/life-threatening bleeding (RR 0.93; 95% CI: 0.72-1.21, p-value 0.61) and minor bleeding (RR 0.96; 95% CI: 0.74-1.23; p-value 0.72) were similar between VKA and DOACs.
CONCLUSION
Considering the totality of available evidence, in patients who underwent TAVR with a concomitant indication for OAC, DOACs-based strategy is an effective and safe anticoagulation strategy compared to VKA.
Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Fibrinolytic Agents; Hemorrhage; Humans; Randomized Controlled Trials as Topic; Stroke; Transcatheter Aortic Valve Replacement; Treatment Outcome; Vitamin K
PubMed: 35901908
DOI: 10.1016/j.ijcard.2022.07.039