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British Journal of Clinical Pharmacology Nov 2022Observational studies have investigated the effectiveness and safety of direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) used in nonvalvular atrial... (Meta-Analysis)
Meta-Analysis Review
Effectiveness and safety of intracranial events associated with the use of direct oral anticoagulants for atrial fibrillation: A systematic review and meta-analysis of 92 studies.
AIMS
Observational studies have investigated the effectiveness and safety of direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) used in nonvalvular atrial fibrillation. We performed a systematic review and meta-analysis assessing the risk of ischaemic stroke, thromboembolism (TE) and intracranial haemorrhage (ICH) associated with the use of DOACs and VKAs.
METHODS
Medline and Embase were systematically searched until April 2021. Observational studies were gathered and hazard ratios (HRs) with 95% confidence intervals (CI) were extracted. Subgroup analyses based on DOAC doses, history of chronic kidney disease, stroke, exposure to VKA, age and sex were performed. A random-effects model was used.
RESULTS
We included 92 studies and performed 107 comparisons. Apixaban was associated with lower risk of stroke (HR: 0.82, 95% CI: 0.68-0.99) compared to dabigatran. Rivaroxaban was associated with lower risk of stroke (HR: 0.90, 95% CI: 0.83-0.98) compared to VKA. Dabigatran (HR: 0.85, 95% CI: 0.80-0.91), rivaroxaban (HR: 0.83, 95% CI: 0.77-0.89) and apixaban (HR: 0.75, 95% CI: 0.65-0.86) were associated with lower risk for TE/stroke compared to VKA. Apixaban (HR: 1.32, 95% CI: 1.03-1.68) and rivaroxaban (HR: 1.58, 95% CI: 1.31-1.89) were associated with higher risk of ICH compared to dabigatran. Dabigatran (HR: 0.48, 95% CI: 0.44-0.52), apixaban (HR: 0.60, 95% CI: 0.49-0.73) and rivaroxaban (HR: 0.73, 95% CI: 0.65-0.81) were associated with lower risk of ICH compared to VKA.
CONCLUSION
Our study demonstrated significant differences in the risk of ischaemic stroke, TE/stroke and ICH associated with individual DOACs compared to both other DOACs and VKA.
Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Dabigatran; Humans; Intracranial Hemorrhages; Ischemic Stroke; Pyridones; Rivaroxaban; Stroke; Thromboembolism; Vitamin K
PubMed: 35853612
DOI: 10.1111/bcp.15464 -
Seminars in Dialysis Nov 2022Non-vitamin K oral anticoagulants (NOACs) are used for prevention of thromboembolic events, but their use in dialysis patients is debatable. This study investigated the...
Non-vitamin K oral anticoagulants (NOACs) are used for prevention of thromboembolic events, but their use in dialysis patients is debatable. This study investigated the available evidence for the use of NOACs in dialysis patients. Online databases were systematically searched for eligible studies including pharmacokinetic (PK) studies, cohort studies, and randomized control trials (RCTs) comparing NOAC with vitamin K antagonist (VKA) or no anticoagulant treatment. Newcastle Ottawa Scale and Cochrane Risk of bias tool were used for quality assessment. Twenty studies were identified (nine PK studies, two RCTs, and nine cohort studies). Most of the studies investigated apixaban or rivaroxaban. In dialysis patients, less accumulation was reported with apixaban and rivaroxaban compared to dabigatran and edoxaban. PK studies indicate that high dose apixaban or rivaroxaban should be avoided. The two RCTs (rivaroxaban/apixaban vs. VKA) were small and underpowered regarding stroke and bleeding outcomes. Most cohort studies found apixaban superior to VKA, whereas comparison of rivaroxaban with VKA yielded conflicting results. Cohort studies comparing apixaban high dose (5 mg) with low dose (2.5 mg) twice daily suggest a lower risk of stroke with high dose but also a higher risk of bleeding with high dose. Apixaban versus no anticoagulation was compared in one cohort study and did not lower the risk of stroke compared with non-treated regardless of apixaban dosage. Widespread use of NOACs in dialysis patients is limited by adequately sized RCTs. Available evidence suggests a potential for use of apixaban and rivaroxaban in reduced dose.
Topics: Humans; Vitamin K; Rivaroxaban; Administration, Oral; Renal Dialysis; Anticoagulants; Dabigatran; Stroke; Hemorrhage; Atrial Fibrillation
PubMed: 35623902
DOI: 10.1111/sdi.13098 -
Current Problems in Cardiology Aug 2023
Meta-Analysis Review
Head-to-head Comparison Between Direct Oral Anticoagulants and Vitamin K Antagonists for Chronic Thromboembolic Pulmonary Hypertension: A Systematic Review and Meta-Analysis.
Topics: Humans; Hypertension, Pulmonary; Anticoagulants; Fibrinolytic Agents; Vitamin K; Administration, Oral; Atrial Fibrillation
PubMed: 35500739
DOI: 10.1016/j.cpcardiol.2022.101232 -
Journal of Cardiovascular Pharmacology Jun 2022Left ventricular thrombi (LVTs) increase the risk of stroke, systemic embolism, and subsequent death. Current guidelines recommend vitamin K antagonists (VKAs) as... (Meta-Analysis)
Meta-Analysis
Direct Oral Anticoagulants Versus Vitamin K Antagonists for the Treatment of Left Ventricular Thrombus: An Updated Meta-Analysis of Cohort Studies and Randomized Controlled Trials.
Left ventricular thrombi (LVTs) increase the risk of stroke, systemic embolism, and subsequent death. Current guidelines recommend vitamin K antagonists (VKAs) as first-line treatment for LVT. Direct oral anticoagulants (DOACs) are increasingly used as alternatives to warfarin for the treatment of LVT. However, the efficacy and safety of DOACs versus VKAs remain controversial. Thus, we conducted an updated meta-analysis of DOACs versus VKAs for LVT treatment. We systematically searched PubMed, Embase, ClinicalTrials, and Cochrane Library databases for relevant articles published before December 11, 2021. The relative risks (RRs) with 95% confidence intervals (CIs) were calculated for each study. The meta-analysis included 12 cohort studies and 3 randomized controlled trials with a total of 2334 patients. We found that DOACs had a lower risk of clinically significant bleeding than VKAs (RR = 0.6; 95% CI, 0.39 to 0.90; P = 0.01; I2 = 0%). There was no difference in LVT resolution (RR = 1.01; 95% CI, 0.93 to 1.09; P = 0.48; I2 = 0%), stroke and/or systematic embolic events (RR = 0.87; 95% CI, 0.11 to 1.55; P = 0.2; I2 = 30%), and all-cause mortality (RR = 0.9; 95% CI, 0.58 to 1.4; P = 0.65; I2 = 0%). Overall, DOACs are noninferior to warfarin in LVT treatment but have a lower risk of clinically significant bleeding. This suggests that DOACs might be better alternatives to warfarin for LVT treatment.
Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Cohort Studies; Fibrinolytic Agents; Hemorrhage; Humans; Randomized Controlled Trials as Topic; Stroke; Thrombosis; Vitamin K; Warfarin
PubMed: 35383658
DOI: 10.1097/FJC.0000000000001270 -
European Review For Medical and... Oct 2021Elderly patients with hip fractures are frequently under anticoagulant therapy. We aimed to assess if outcomes of hip fracture patients undergoing surgical intervention... (Comparative Study)
Comparative Study Meta-Analysis
OBJECTIVE
Elderly patients with hip fractures are frequently under anticoagulant therapy. We aimed to assess if outcomes of hip fracture patients undergoing surgical intervention differ with prior use of direct oral anticoagulants (DOAC) or Vitamin K antagonists (VKA).
MATERIALS AND METHODS
PubMed, Embase, and Google Scholar were searched for comparative studies published up to June 20, 2021. Dichotomous variables were summarized using odds ratio (OR) and continuous variables using mean difference (MD).
RESULTS
Fourteen studies were included. There was no difference in the time to surgery between patients on DOAC or VKA (MD: 2.50 95% CI -2.10, 7.10 I2=76% p=0.29). Number of undergoing surgeries within 48 hours was not significantly different between the two groups (OR: 0.77 95% CI 0.56, 1.06 I2=10% p=0.10). Mortality rates (OR: 0.84 95% CI 0.62, 1.14 I2=12% p=0.27), blood transfusion requirement (OR: 1.08 95% CI 0.80, 1.47 I2=30% p=0.62) and length of hospital stay (MD: 0.26 95% CI -0.70, 1.21 I2=0% p=0.60) was also not significantly different between patients on DOAC or VKA.
CONCLUSIONS
There is no difference in surgical delay, early mortality, blood transfusion rates and length of hospital stay between DOAC uses and VKA users undergoing hip fracture surgery.
Topics: Aged; Anticoagulants; Blood Transfusion; Hip Fractures; Humans; Length of Stay; Time Factors; Vitamin K
PubMed: 34730205
DOI: 10.26355/eurrev_202110_26995 -
BMJ Evidence-based Medicine Aug 2022To assess cost-effectiveness of direct oral anticoagulants (DOACs) compared with vitamin K antagonists (VKAs) for stroke prevention in atrial fibrillation (AF) by... (Meta-Analysis)
Meta-Analysis
Economic evaluation of direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs) for stroke prevention in patients with atrial fibrillation: a systematic review and meta-analysis.
OBJECTIVES
To assess cost-effectiveness of direct oral anticoagulants (DOACs) compared with vitamin K antagonists (VKAs) for stroke prevention in atrial fibrillation (AF) by pooling incremental net benefits (INBs).
DESIGN
Systematic review and meta-analysis.
SETTING
We searched PubMed, Scopus and Centre for Evaluation of Value and Risks in Health Registry from inception to December 2019.
PARTICIPANTS
Patients with AF.
MAIN OUTCOME MEASURES
The INB was defined as a difference of incremental effectiveness multiplied by willing to pay threshold minus the incremental cost; a positive INB indicated favour treatment. These INBs were pooled (stratified by level of country income, perspective, time-horizon, model types) with a random-effects model if heterogeneity existed, otherwise a fixed effects model was applied. Heterogeneity was assessed using Q test and I statistic. Risk of bias was assessed using the economic evaluations bias (ECOBIAS) checklist.
RESULTS
A total of 100 eligible economic evaluation studies (224 comparisons) were included. For high-income countries (HICs) from a third-party payer (TPP) perspective, the pooled INBs for DOAC versus VKA pairs were significantly cost-effective with INBs (95% CI) of $6632 ($2961.67 to $10 303.72; I=59.9%), $6353.24 ($4076.03 to $8630.45; I=0%), $7664.58 ($2979.79 to $12 349.37; I=0%) and $8573.07 ($1877.05 to $15 269.09; I=0%) for dabigatran, apixaban, rivaroxaban and edoxaban relative to VKA, respectively but only dabigatran was significantly cost-effective from societal perspective (SP) with an INB of $11 746.96 ($2429.34 to $21 064.59; I=52.4%). The pooled INBs of all comparisons for upper-middle income countries (UMICs) were not significantly cost-effective. The ECOBIAS checklist indicated that risk of bias was mostly low for most items with the exception of five items which should be less influenced on pooling INBs.
CONCLUSIONS
Our meta-analysis provides comprehensive economic evidence that allows policy makers to generalise cost-effectiveness data to their local context. All DOACs may be cost-effective compared with VKA in HICs with TPP perspective. The pooling results produced moderate to high heterogeneity particularly in UMICs. Further studies are required to inform UMICs with SP.
PROSPERO REGISTERATION NUMBER
CRD 42019146610.
Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Cost-Benefit Analysis; Dabigatran; Fibrinolytic Agents; Humans; Stroke; Vitamin K
PubMed: 34635480
DOI: 10.1136/bmjebm-2020-111634 -
European Review For Medical and... Aug 2021To compare the outcomes between direct-acting oral anticoagulants and vitamin K antagonists, particularly for risk of stroke and bleeding, among patients with atrial... (Comparative Study)
Comparative Study Meta-Analysis
Comparison of outcomes of direct-acting oral anticoagulants vs. vitamin K antagonists in patients with bioprosthetic heart valves or valve repair: a systematic review and meta-analysis.
OBJECTIVE
To compare the outcomes between direct-acting oral anticoagulants and vitamin K antagonists, particularly for risk of stroke and bleeding, among patients with atrial fibrillation (AF) and bioprosthetic heart valve replacement or repair.
MATERIALS AND METHODS
A systematic search was conducted in the PubMed, Scopus, Cochrane Database of Systematic Reviews and Google scholar databases. Studies that were done in patients with AF who underwent bioprosthetic heart valve replacement or repair and that compared the outcomes between the use of direct-acting oral anticoagulants (DOACs) and vitamin K antagonists were eligible for inclusion. Studies that were preferably randomized controlled trials or adopted a cohort approach or retrospective data-based studies were considered for inclusion. The strength of association was presented in the form of pooled hazards risk (HR). Statistical analysis was done using STATA version 16.0.
RESULTS
A total of 8 articles were included in the meta-analysis. There were no significant differences in the risk of "all-cause stroke" [HR 0.72, 95% CI: 0.39, 1.34] and ischemic stroke [HR 0.79, 95% CI: 0.49, 1.29] between the two groups. The risk of "any bleeding" [HR 0.74, 95% CI: 0.64, 0.87], major bleeding [HR 0.60, 95% CI: 0.42, 0.86] and intra-cranial bleeding [HR 0.54, 95% CI: 0.36, 0.81] was much lower in those that received DOAC compared to warfarin. Compared to those receiving warfarin, those on DOACs had substantially reduced risk of any clinical thromboembolic events [HR 0.52, 95% CI: 0.39, 0.70]. No significant differences were noted for all-cause mortality [HR 0.88, 95% CI: 0.74, 1.05], cardiovascular events/myocardial infarction (MI) [HR 0.58, 95% CI: 0.33, 1.04] and and readmission rates [HR 0.85, 95% CI: 0.62, 1.18].
CONCLUSIONS
Findings suggest that the use DOACs in patients with AF with bioprosthetic valve replacement or repair is comparatively better than vitamin K antagonists in reducing the risk of bleeding and thrombo-embolic events. Future studies with a randomized design and larger sample sizes are needed to further substantiate these findings.
Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Factor Xa Inhibitors; Heart Valves; Humans; Vitamin K
PubMed: 34355372
DOI: 10.26355/eurrev_202108_26457 -
The British Journal of Nutrition Jul 2022Hyperemesis gravidarum (HG), severe nausea and vomiting in pregnancy, can lead to vitamin deficiencies. Little is known about HG-related vitamin K deficiency. We aimed...
Hyperemesis gravidarum (HG), severe nausea and vomiting in pregnancy, can lead to vitamin deficiencies. Little is known about HG-related vitamin K deficiency. We aimed to summarise available evidence on the occurrence of HG-related vitamin K deficiency and corresponding maternal and neonatal complications. A systematic review was conducted, searching Medline and EMBASE from inception to 12 November 2020. We identified 1564 articles, of which we included fifteen in this study: fourteen case reports ( 21 women) and one retrospective cohort study ( 109 women). Nine out of twenty-one women reported in case reports had a prolonged prothrombin time (PT). The cohort study measured PT in 39/109 women with HG, of whom 10/39 women (26 %) had prolonged PT. In total, 30-50 % women received vitamin K supplementation after vitamin K deficiency had been diagnosed. Four case reports ( 4 women) reported corresponding maternal complications, all consisting of coagulopathy-related haemorrhage. Nine case reports ( 16 neonates) reported corresponding neonatal complications including intracranial haemorrhage ( 2 neonates) and embryopathy ( 14 neonates), which consisted of Binder phenotype ( 14 neonates), chondrodysplasia punctata ( 9 neonates) and grey matter heterotopia ( 3 neonates). In conclusion, vitamin K deficiency and related complications occur among women with HG. In our systematic review, we were unable to assess the incidence rate.
Topics: Pregnancy; Humans; Female; Male; Hyperemesis Gravidarum; Cohort Studies; Retrospective Studies; Vitamin K Deficiency; Vitamin K
PubMed: 34325760
DOI: 10.1017/S0007114521002865 -
PloS One 2021Although several meta-analyses have compared efficacies of vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs) for treatment of left ventricular thrombus... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Although several meta-analyses have compared efficacies of vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs) for treatment of left ventricular thrombus (LVT), those meta-analyses included no single-arm studies.
METHODS AND RESULTS
PubMed, Scopus, and the Cochrane Library databases were searched for articles investigating thrombus resolution, stroke, any thromboembolism, major bleeding, any bleeding, or all-cause death in LVT treated with VKAs or DOACs, and single-class meta-analyses were also included (PROSPERO database, CRD42021230849). Event rates were pooled using a random effects model. Meta-regression analysis was performed to explore factors that may influence outcomes. 2,612 patients from 23 articles were included (VKAs: 2,004, DOACs: 608). There were no significant differences between VKAs and DOACs in the frequency of thrombus resolution (VKAs: 0.75 [95% confidence interval; 0.67 to 0.81], DOACs: 0.75 [0.67 to 0.82]), stroke (VKAs: 0.06 [0.04 to 0.10], DOACs: 0.02 [0.01 to 0.01]), any thromboembolism (VKAs: 0.08 [0.05 to 0.13], DOACs: 0.03 [0.01 to 0.10]), major bleeding (VKAs: 0.06 [0.04 to 0.09], DOACs: 0.03 [0.01 to 0.06]), any bleeding (VKAs: 0.08 [0.05 to 0.12], DOACs: 0.08 [0.06 to 0.10]), and all-cause death (VKAs: 0.07 [0.04 to 0.13], DOACs: 0.09 [0.05 to 0.16]). Meta-regression analysis revealed that increased duration of follow-up was associated with lower-rates of stroke (estimate: -0.040, p = 0.0495) with VKAs, but not with DOACs. There was significant publication bias for thrombus resolution, stroke, any thromboembolism, any bleeding, and all-cause death.
CONCLUSIONS
Efficacy and adverse outcomes of therapy with DOACs and VKAs do not differ. Randomized controlled trials are needed to determine the optimal anticoagulant strategy.
Topics: Administration, Oral; Anticoagulants; Heart Ventricles; Hemorrhage; Humans; International Normalized Ratio; Stroke; Thromboembolism; Thrombosis; Vitamin K
PubMed: 34310654
DOI: 10.1371/journal.pone.0255280 -
RMD Open Jul 2021Despite vitamin K antagonists (VKA) being the gold standard in the prevention of thromboembolic events in antiphospholipid syndrome (APS), non-vitamin K antagonists oral... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Despite vitamin K antagonists (VKA) being the gold standard in the prevention of thromboembolic events in antiphospholipid syndrome (APS), non-vitamin K antagonists oral anticoagulants/direct oral anticoagulants (DOACs) have been used off-label.
OBJECTIVE
We aimed to perform a systematic review comparing DOACs to VKA regarding prevention of thromboembolic events, occurrence of bleeding events and mortality in patients with APS.
METHODS
An electronic database search was performed through MEDLINE, CENTRAL and Web of Science. After data extraction, we pooled the results using risk ratio (RR) and 95% CI. Heterogeneity was assessed using the I². The outcomes considered were all thromboembolic events as primary, and major bleeding, all bleeding events and mortality as secondary. Evidence confidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation methodology.
RESULTS
We included 7 studies and a total of 835 patients for analyses. Thromboembolic events were significantly increased in DOACs arm, compared with VKA-RR 1.69, 95% CI 1.09 to 2.62, I²-24%, n=719, 6 studies. In studies using exclusively rivaroxaban, which was the most representative drug in all included studies, the thromboembolic risk was increased threefold (RR 3.36, 95% CI 1.53 to 7.37). The risks of major bleeding, all bleeding events and mortality were not significantly different from control arm. The grade of certainty of our results is very low.
CONCLUSIONS
Current evidence suggests DOACs use, particularly rivaroxaban, among patients with APS, is less effective than VKA since it is associated with 69% increased risk of thromboembolic events.
TRIAL REGISTRATION NUMBER
CRD42020216178.
Topics: Anticoagulants; Antiphospholipid Syndrome; Hemorrhage; Humans; Rivaroxaban; Vitamin K
PubMed: 34253684
DOI: 10.1136/rmdopen-2021-001678