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European Journal of Clinical... Oct 2022Transcatheter aortic valve replacement (TAVR) is increasingly carried out in patients with aortic valvular conditions. Atrial fibrillation (AF) is a common comorbidity... (Meta-Analysis)
Meta-Analysis Review
A systematic review and meta-analysis of non-vitamin K antagonist oral anticoagulants vs vitamin K antagonists after transcatheter aortic valve replacement in patients with atrial fibrillation.
PURPOSE
Transcatheter aortic valve replacement (TAVR) is increasingly carried out in patients with aortic valvular conditions. Atrial fibrillation (AF) is a common comorbidity among patients undergoing TAVR. Despite this, there remains a paucity of data and established guidelines regarding anticoagulation use post-TAVR in patients with AF.
METHODS
Four databases were searched from inception until 12 October 2021. A title and abstract sieve, full-text review and data extraction were conducted by independent authors, and articles including patients without AF were excluded. The Review Manager (Version 5.4) was utilised in data analysis.
RESULTS
A total of 25,199 post-TAVR patients with AF were included from seven articles, with 9764 patients on non-vitamin K antagonist oral anticoagulants (NOAC) and 15,435 patients on vitamin K antagonists (VKA). In this analysis, there was a significantly lower risk of all-cause mortality at 1 year (RR: 0.75, CI: 0.58-0.97, p = 0.04, I = 56%), and bleeding at 1 year (RR: 0.73, CI: 0.68-0.79, p = < 0.00001, I = 0%), between patients on NOAC and VKA. There were no detectable differences between patients on NOAC and VKA for all-cause mortality at 2 years, stroke within 30 days, stroke within 1 year, ischaemic stroke at 1 year and life-threatening bleeding at 30 days.
CONCLUSION
While the results of this analysis reveal NOAC as a potential alternate treatment modality to VKA in post-TAVR patients with AF, further research is needed to determine the full safety and efficacy profile of NOAC (PROSPERO: CRD42021283548).
Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Fibrinolytic Agents; Hemorrhage; Humans; Stroke; Transcatheter Aortic Valve Replacement; Treatment Outcome
PubMed: 35941300
DOI: 10.1007/s00228-022-03371-6 -
Heart & Lung : the Journal of Critical... 2014Atrial fibrillation (AF), a common arrhythmia, increases the risk of ischemic stroke. Stroke and bleeding scores for patients with AF can help to stratify risk and... (Review)
Review
Atrial fibrillation (AF), a common arrhythmia, increases the risk of ischemic stroke. Stroke and bleeding scores for patients with AF can help to stratify risk and determine the need for antithrombotic therapy, for which warfarin has been the gold standard. Although highly effective, warfarin has several limitations that can lead to its underuse. Data from randomized, Phase III clinical trials of the novel oral anticoagulants, dabigatran, a direct thrombin inhibitor, and rivaroxaban and apixaban, both factor Xa inhibitors, indicate these drugs are at least noninferior to warfarin for the prevention of stroke and systemic embolism. They are easier to administer, and have an equivalent or lower risk of bleeding versus warfarin. A better understanding of the risks and benefits of the novel oral anticoagulants, and their use in clinical practice, will prepare clinicians to anticipate and address educational and clinical needs of AF patients and their families, and promote evidence-based prescription of appropriate and safe anticoagulation therapy.
Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Benzimidazoles; Dabigatran; Hemorrhage; Humans; Morpholines; Platelet Aggregation Inhibitors; Pyrazoles; Pyridones; Risk Assessment; Rivaroxaban; Stroke; Thiophenes; Warfarin; beta-Alanine
PubMed: 24373340
DOI: 10.1016/j.hrtlng.2013.10.014 -
Frontiers in Pharmacology 2021There is controversy over whether use of new oral anticoagulants (NOACs) associates with increased hemorrhage risk compared with non-NOAC. Meanwhile, determining which... (Review)
Review
There is controversy over whether use of new oral anticoagulants (NOACs) associates with increased hemorrhage risk compared with non-NOAC. Meanwhile, determining which NOAC to use remains unclear. We aimed to summarize the evidence about NOACs in venous thromboembolism (VTE) prevention for patients with total hip and knee arthroplasty (THA and TKA). We searched RCTs assessing NOACs for VTE prophylaxis in adults undergoing THA and TKA in Medline, Embase, and Cochrane up to May 2021. Primary outcomes were VTE [included deep vein thrombosis (DVT) and pulmonary embolism (PE)], major VTE, and major bleeding. The rank probabilities of each treatment were summarized by the surface under the cumulative ranking curve area (SUCRA). 25 RCTs with 42,994 patients were included. Compared with non-NOAC, NOACs were associated with a decreased risk of VTE (RR 0.68; 95% CI 0.55-0.84) and major VTE (RR = 0.52; 95% CI 0.35-0.76). Additionally, rivaroxaban, apixaban, and edoxaban but not dabigatran and betrixaban, did confer a higher efficacy compared with non-NOAC. None of the individual NOACs increased the risk of bleeding, while apixaban and betrixaban were even associated with a decreased risk of bleeding. In the comparison of different NOACs, rivaroxaban was associated with the greatest benefits in VTE (SUCRA = 79.6), DVT (SUCRA = 88.8), and major VTE (SUCRA = 89.9) prevention. Furthermore, subgroup analysis confirmed that NOACs associated with a higher efficacy tendency in patients with follow-up duration <60 days than follow-up duration ≥60 days. Evidence suggests that NOACs exert more benefits on VTE prophylaxis, and none of the individual NOACs increased hemorrhage compared with non-NOAC. Among various NOACs, rivaroxaban is recommended in patients with lower bleeding risk, and apixaban is recommended in patients with higher bleeding risk. : [https://www.crd.york.ac.uk/prospero/], identifier [CRD42021266890].
PubMed: 35111051
DOI: 10.3389/fphar.2021.775126 -
Clinical Gastroenterology and... Apr 2020There is controversy over whether use of non-vitamin K antagonist oral anticoagulants (NOACs) associates with increased risk of major gastrointestinal bleeding (GIB)... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND & AIMS
There is controversy over whether use of non-vitamin K antagonist oral anticoagulants (NOACs) associates with increased risk of major gastrointestinal bleeding (GIB) compared with conventional therapies (such as vitamin K antagonists or anti-platelet agents). We performed a systematic review and meta-analysis of data from randomized controlled trials and high-quality real-world studies.
METHODS
We performed a systematic search of the MEDLINE, EMBASE, Cochrane Library, and ClinicalTrials.gov Website databases (through Oct 12, 2018) for randomized controlled trials and high-quality real-world studies that reported major GIB events in patients given NOACs or conventional therapy. Relative risks (RRs) for randomized controlled trials and adjusted hazard ratios (aHRs) for real-world studies were calculated separately using random-effects models.
RESULTS
We analyzed data from 43 randomized controlled trials (183,752 patients) and 41 real-world studies (1,879,428 patients). The pooled major rates of GIB for patients on NOACs (1.19%) vs conventional treatment (0.92%) did not differ significantly (RR from randomized controlled trials, 1.09; 95% CI, 0.91-1.31 and aHR from real-world studies, 1.02; 95% CI, 0.94-1.10; P=.52). Rivaroxaban, but not other NOACs, was associated with an increased risk for major GIB (RR from randomized controlled trials, 1.39; 95% CI, 1.17-1.65 and aHR from real-world studies, 1.14; 95% CI, 1.04-1.23; P = .06). Analyses of subgroups, such as patients with different indications, dosage, or follow-up time, did not significantly affect results. Meta-regression analysis failed to detect any potential confounding to impact the primacy outcome.
CONCLUSIONS
In a systematic review and meta-analysis of data from randomized controlled trials and real-world studies, we confirmed that there is no significant difference in risk of major GIB between patients receiving NOACs vs conventional treatment. Rivaroxaban users had a 39% increase in risk for major GIB.
Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Fibrinolytic Agents; Gastrointestinal Hemorrhage; Humans; Rivaroxaban; Stroke
PubMed: 31195162
DOI: 10.1016/j.cgh.2019.05.056 -
Journal of Clinical Neuroscience :... Apr 2019Direct Oral Anticoagulants (DOAC) are increasingly used as an alternative to vitamin-K antagonists (VKA) for anticoagulation and have shown lower rates of intracranial... (Meta-Analysis)
Meta-Analysis
Direct Oral Anticoagulants (DOAC) are increasingly used as an alternative to vitamin-K antagonists (VKA) for anticoagulation and have shown lower rates of intracranial hemorrhage; however, there is disagreement in the literature over the outcomes of the intraparenchymal hemorrhages (IPH) associated with DOACs, and clinical concern regarding the lack of standardized reversal strategies for DOACs. Thus, the aim of this meta-analysis was to compare mortality, hematoma volume, and risk of hematoma expansion in patients who developed an IPH on DOACs versus VKA. A systematic review of the literature was conducted in accordance with the PRISMA guidelines. Studies were selected that reported on mortality, hematoma expansion, and hematoma volume in DOAC-associated IPH. Pooled risk ratios (RR) were calculated for mortality and hematoma expansion and pooled mean difference (MD) was calculated for hematoma volume (ml) using random-effect models. 15 studies reporting on 1238 patients were included in the systematic review. Eleven of these compared DOAC-IPH to VKA-IPH and were pooled quantitatively. DOAC-IPH was not associated with increased mortality risk (RR: 0.95, 95%-CI: 0.72 -1.27) or increased hematoma expansion risk (RR: 0.92; 95%-CI: 0.75-1.12) compared to VKA-IPH. The hematoma volume of DOAC- IPH was statistically significantly smaller than VKA-IPH (MD: -12.14 ml; 95%-CI: -15.38; -8.89). In conclusion, DOAC-IPH was not associated with increased mortality or hematoma expansion compared to VKA-IPH and may be associated with a smaller hematoma volume.
Topics: Administration, Oral; Anticoagulants; Blood Coagulation; Cerebral Hemorrhage; Hematoma; Humans; Male; Risk Factors; Vitamin K
PubMed: 30472344
DOI: 10.1016/j.jocn.2018.11.032 -
Neurology India 2022Both early surgery and delayed surgery of ruptured arteriovenous malformation (AVM) with intracerebral hemorrhages have their own advantages and disadvantages. Due to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Both early surgery and delayed surgery of ruptured arteriovenous malformation (AVM) with intracerebral hemorrhages have their own advantages and disadvantages. Due to lack of large case-control studies, timing of surgery for ruptured AVM excision is still a controversial topic. So, we did a systemic review and meta-analysis, including our experience of early surgery, to see which surgical strategy has a favorable outcome.
MATERIALS AND METHODS
We systematically searched several databases and journals to screen eligible studies. After synthesizing data, results of individual studies of early and delayed surgery were calculated as the effect size (ES) and 95% confident intervals (CIs), and the pooled ES was calculated using random-effects model. Heterogeneity and publication bias were assessed for the individual outcomes.
RESULTS
A total of nine published studies, one oral presentation, and our unpublished study were included in the analysis. Delayed surgery has better results than early surgery in terms of complete excision rate (delayed ES, 1.00; 95% CI, 0.97 1.00 vs. early ES, 0.96; 95% CI, 0.91 0.99), good functional outcome (delayed ES, 0.94; 95% CI, 0.86 0.99 vs. early ES, 0.68; 95% CI, 0.51 0.84), and mortality (delayed ES, 0.00; 95% CI, 0.00 0.01 vs. early ES, 0.04; 95% CI, 0.01 0.10). Heterogeneity was significant in the results of early surgery group, and no publication bias was found in the meta-analysis.
CONCLUSION
Delayed surgery is superior to early surgery in achieving higher complete excision rate, good functional outcome, and reducing mortality. However, larger comparative studies are needed for subgroup analysis and for reducing the impact of various confounding factors.
Topics: Humans; Treatment Outcome; Intracranial Arteriovenous Malformations; Cerebral Hemorrhage; Case-Control Studies; Databases, Factual
PubMed: 36537413
DOI: 10.4103/0028-3886.364074 -
Therapeutic Advances in Cardiovascular... 2022Oral anticoagulation with direct oral anticoagulants (DOAC) could provide an alternative to vitamin K antagonists (VKA) for patients with atrial fibrillation (AF)... (Meta-Analysis)
Meta-Analysis
AIMS
Oral anticoagulation with direct oral anticoagulants (DOAC) could provide an alternative to vitamin K antagonists (VKA) for patients with atrial fibrillation (AF) undergoing bioprosthetic heart valve replacement or valve repair.
METHODS AND RESULTS
The aim of this meta-analysis was to review the safety and efficacy of DOAC in patients with surgical implanted bioprosthetic heart valves or valve repairs and AF including data from six clinical trials with a total of 1,857 patients. The efficacy and safety data of DOAC and VKA were pooled to perform random-effects meta-analyses using the Mantel-Haenszel method with pooled risk ratios (RR) and 95% confidence interval (CI). A trial sequential analysis (TSA) was performed to assess statistical robustness. Death caused by cardiovascular cause or thromboembolic events were comparable (RR 0.67, 95% CI: 0.42-1.08; = 0.10) as DOAC significantly reduced the risk for major bleeding (RR 0.55, 95% CI: 0.35-0.88; = 0.01) and thromboembolic stroke or systemic embolism rates (RR 0.54, 95% CI: 0.32-0.90; = 0.02). Rates for intracranial bleeding and hemorrhagic stroke (RR 0.27, 95% CI: 0.07-0.99; = 0.05) show a trend toward fewer events in the DOAC group. Outcomes for major or minor bleeding events and all-cause mortality were comparable for DOAC and VKA.
CONCLUSION
Cumulative data analysis reveals that DOAC may provide an effective and safe alternative to VKA in patients with AF after surgically implanted bioprosthetic heart valves or repair with AF. Within a relatively heterogeneous study population, this meta-analysis shows a risk reduction of major bleedings and thromboembolic stroke or systemic embolisms for DOAC.
Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Hemorrhage; Humans; Stroke; Thromboembolism
PubMed: 35481366
DOI: 10.1177/17539447221093963 -
Journal of Thrombosis and Haemostasis :... Jul 2018Essentials Risk of intracranial hemorrhage (ICH) may differ between direct oral anticoagulants (DOACs). We compared the risk of ICH between DOACs using network... (Meta-Analysis)
Meta-Analysis
UNLABELLED
Essentials Risk of intracranial hemorrhage (ICH) may differ between direct oral anticoagulants (DOACs). We compared the risk of ICH between DOACs using network meta-analysis. Dabigatran 110 mg and 150 mg were safer than rivaroxaban on Bayesian analysis. Dabigatran 110 mg ranked as the safest DOAC while rivaroxaban ranked last.
SUMMARY
Background The comparative risk of intracranial hemorrhage (ICH) among direct oral anticoagulants (DOACs) (dabigatran, rivaroxaban, apixaban and edoxaban) remains unclear. Objective To determine the difference in risk of ICH between DOACs Methods Seventeen randomized controlled trials (RCTs) were selected using PubMed/MEDLINE, EMBASE and CENTRAL (Inception, 31 December 2017). Estimates were reported as odds ratio (OR) with 95% credible interval (CR.I) in Bayesian network meta-analysis (NMA), and OR with 95% confidence interval (CI) in traditional meta-analyses. Relative ranking probability of each group was generated based on surface under the cumulative ranking curve (SUCRA). Results In NMA of 116 618 patients from 17 RCTs (apixaban = 19 495 patients, rivaroxaban = 14 157 patients, dabigatran = 16 074 patients, edoxaban = 11 652 patients, and comparator = 55 315 patients), all DOACs were safer than warfarin for risk of ICH. Dabigatran 110 mg ranked as the safest drug (SUCRA, 0.85) and reduced the risk of ICH by 56% compared to rivaroxaban (OR, 0.44; 95% Cr.I, 0.22-0.82). Pairwise meta-analysis validated these findings, showing that DOACs were safer than warfarin (OR, 0.46; 95% CI, 0.35-0.59). Subgroup analysis showed that the benefit was present when DOACs were used in non-valvular atrial fibrillation (NVAF) (OR, 0.51; 95% CI, 0.38-0.68) or venous thromboembolism (VTE) (OR, 0.32; 95% CI, 0.18-0.58). Conclusion Dabigatran 110 mg may be the safest choice among any anticoagulant regarding risk of ICH. Both dabigatran 110 mg and 150 mg were safer than rivaroxaban.
Topics: Administration, Oral; Antithrombins; Bayes Theorem; Dabigatran; Factor Xa Inhibitors; Humans; Intracranial Hemorrhages; Pyrazoles; Pyridines; Pyridones; Risk Assessment; Risk Factors; Rivaroxaban; Thiazoles; Treatment Outcome
PubMed: 29723935
DOI: 10.1111/jth.14131 -
Journal of Thrombosis and Thrombolysis Mar 2024In patients with atrial fibrillation (AF) and normal or slightly impaired renal function, the use of direct oral anticoagulants (DOACs) is preferable to vitamin K... (Meta-Analysis)
Meta-Analysis
Direct oral anticoagulants versus vitamin K antagonists in patients with atrial fibrillation and stage 5 chronic kidney disease under dialysis: A systematic review and meta-analysis of randomized controlled trials.
BACKGROUND
In patients with atrial fibrillation (AF) and normal or slightly impaired renal function, the use of direct oral anticoagulants (DOACs) is preferable to vitamin K antagonists (VKAs). However, in patients undergoing hemodialysis, the efficacy, and safety of DOACs compared with VKAs are still unknown.
PURPOSE
To review current evidence about the safety and efficacy of DOACs compared to VKAs, in patients with AF and chronic kidney disease under hemodialysis.
METHODS
We systematically searched PubMed, Scopus, and Cochrane databases for RCTs comparing DOACs with VKAs for anticoagulation in patients with AF on dialysis therapy. Outcomes of interest were: (1) stroke; (2) major bleeding; (3) cardiovascular mortality; and (4) all-cause mortality. Statistical analysis was performed using RevMan 5.1.7 and heterogeneity was assessed by I statistics.
RESULTS
Three randomized controlled trials were included, comprising a total of 383 patients. Of these, 218 received DOACs (130 received apixaban; 88 received rivaroxaban), and 165 were treated with VKAs (116 received warfarin; 49 received phenprocoumon). The incidence of stroke was significantly lower in patients treated with DOACs (4.7%) compared with those using VKAs (9.5%) (RR 0.42; 95% CI 0.18-0.97; p = 0.04; I = 0%). However, the difference was not statistically significant in the case of ischemic stroke specifically (RR 0.42; 95% CI 0.17-1.04; p = 0.06; I = 0%). As for the major bleeding outcome, the DOAC group (11%) had fewer events than the VKA group (13.9%) but without statistical significance (RR 0.75; 95% CI 0.45-1.28; p = 0.29; I = 0%). There was no significant difference between groups regarding cardiovascular mortality (RR 1.23; 95% CI 0.66-2.29; p = 0.52; I = 13%) and all-cause mortality (RR 0.98; 95% CI 0.77-1.24; p = 0.84; I = 16%).
CONCLUSION
This meta-analysis suggests that in patients with AF on dialysis, the use of DOACs was associated with a significant reduction in stroke, and a numerical trend of less incidence of major bleeding compared with VKAs, but in this case with no statistical significance. Results may be limited by a small sample size or insufficient statistical power.
Topics: Humans; Atrial Fibrillation; Renal Dialysis; Randomized Controlled Trials as Topic; Anticoagulants; Hemorrhage; Stroke; Kidney Failure, Chronic; Fibrinolytic Agents; Vitamin K; Administration, Oral
PubMed: 38281231
DOI: 10.1007/s11239-023-02945-0 -
JAMA Ophthalmology Jul 2015In noninferiority trials, novel oral anticoagulants (NOACs), also known as non-vitamin K oral anticoagulants, were at least noninferior to standard care in the... (Meta-Analysis)
Meta-Analysis Review
IMPORTANCE
In noninferiority trials, novel oral anticoagulants (NOACs), also known as non-vitamin K oral anticoagulants, were at least noninferior to standard care in the prevention of most prothrombotic conditions. However, differences exist in the safety profile of antithrombotic drugs, and little is known about their intraocular bleeding risk.
OBJECTIVE
To evaluate the risk of substantial intraocular bleeding associated with NOACs.
DATA SOURCES
MEDLINE, Cochrane Library, SciELO collection, and Web of Science databases were searched from inception to November 2014, as well as other systematic reviews and regulatory agencies documentation.
STUDY SELECTION
All phase 3 randomized clinical trials (RCTs) comparing NOACs with any other control that reported intraocular bleeding events.
DATA EXTRACTION AND SYNTHESIS
Data were extracted independently by 2 of the authors and pooled using random-effects meta-analysis. Heterogeneity was assessed with the I2 test.
MAIN OUTCOMES AND MEASURES
Substantial intraocular bleeding was evaluated with pooled risk ratios (RRs) and 95% CIs.
RESULTS
Seventeen RCTs were included. In patients with atrial fibrillation, no difference was identified between NOACs and vitamin K antagonists (RR, 0.84; 95% CI, 0.59-1.19; I2 = 35%; 5 RCTs), and no increased risk was identified compared with acetylsalicylic acid (RR, 14.96; 95% CI, 0.85-262.00; 1 RCT). In patients with venous thromboembolism, no increased risk of substantial intraocular bleeding compared with sequential treatment with low-molecular-weight heparin and a vitamin K antagonist (RR, 0.67; 95% CI, 0.37-1.20; I2 = 0%; 5 RCTs) was identified. Regarding patients who underwent orthopedic surgery, the risk was not different between NOACs and low-molecular-weight heparin (RR, 2.13; 95% CI, 0.22-20.50; I2 = 0%; 5 RCTs).
CONCLUSIONS AND RELEVANCE
Randomized data suggest that no differences exist in the risk of substantial intraocular bleeding between NOACs and other antithrombotic drugs. However, the number of events was scarce so that additional studies from larger databases that monitor patients under conditions of ophthalmologic routine clinical practice should be performed to better characterize the safety profile of NOACs.
Topics: Administration, Oral; Anticoagulants; Cardiovascular Diseases; Dose-Response Relationship, Drug; Drug Administration Schedule; Eye Hemorrhage; Female; Humans; Male; Prevalence; Prognosis; Randomized Controlled Trials as Topic; Risk Assessment; Venous Thromboembolism
PubMed: 25950647
DOI: 10.1001/jamaophthalmol.2015.0985