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Thrombosis Research Feb 2021Chronic kidney disease (CKD) increases the risk of venous thromboembolism (VTE) among affected patients. Vitamin K antagonists (VKA) and warfarin remains the main stay... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Chronic kidney disease (CKD) increases the risk of venous thromboembolism (VTE) among affected patients. Vitamin K antagonists (VKA) and warfarin remains the main stay of its treatment. Due to novelty and unclear risk-to-benefit ratio of direct oral anti-coagulants (DOAC), they remain underutilized in preventing VTE among CKD patients. We aim to assess the efficacy and safety of DOACs and other oral anticoagulants in preventing recurrent VTE among high-risk population.
MATERIAL METHODS
We conducted a literature search using PubMed, Embase, Cochrane, Web of Science and Clinicaltrials.gov for randomized controlled trials (RCTs) comparing anti-coagulants like DOAC, LMWH or VKA or any oral anti-coagulant (OAC) (This includes VKAs and DOACs) with either placebo or another anti-coagulant. Two independent reviewers screened the retrieved articles and extracted data using a piloted data extraction sheet. The primary outcome of interest was number of recurrent VTE and other side effects among CKD patients receiving respective treatment. Secondary outcomes were risk of major, non-major and intra-cranial bleed.
RESULTS
We retrieved 7244 titles on initial search, reviewed full text of 818 articles, and selected 10 phase III RCTS for quantitative meta-analysis. Out of 36,326 patients in these trials, only 10,840 (29.8%) were evaluable. We stratified patients into four categories based on severity of renal impairment using serum creatinine clearance (SCr) as the marker e.g. mild (>50 - <80) moderate (>30 - ≤50) severe (<30) and any level (from <30 to <80). There was no difference between DOACs vs VKA in decreasing the risk of recurrent VTE among patients with mild (RR:0.86, 95% CI:0.61-1.22, I = 25%) moderate/severe (RR:0.72, 95% CI:0.44-1.17, I = 0%) or any level of renal impairment (RR:0.83, 95% CI:0.60-1.14, I = 34%). No difference in efficacy between LMWH vs VKA among patients with moderate (RR:2.40, 95% CI:0.44-12.96, I = 76%) and any level (RR:2.59, 95% CI:0.66-10.16, I = 71%) of renal impairment respectively. Similarly, no difference in efficacy between LMWH vs any OAC (This includes VKAs and edoxaban) among patients with (RR:2.16, 95% CI:0.66-7.-06, I = 51%) and any level (RR:1.48, 95% CI:0.79-2.78, I = 78%) of renal impairment. DOACs compared to VKAs had significantly lower risk of combined major and non-major bleeding (RR: 0.74, 95% CI:0.65-0.84, I = 26%), major bleeding (RR: 0.51, 95% CI:0.38-0.69, I = 7%) and non-major clinically relevant bleeding (RR: 0.73, 95% CI:0.57-0.94, I = 45%) respectively. Risk of intracranial bleeding was comparable (RR: 0.68, 95% CI:0.19-2.44, I = 0%). There was no difference in the risk of major bleeding between LMWH vs any OAC (RR: 0.83, 95% CI:0.46-1.51, I = 0%).
CONCLUSION
DOACS and other anticoagulants (VKA and LMWH) showed no statistical difference in preventing recurrent VTEs among CKD patients but DOACs had significantly lower risk of major and non-major clinically relevant bleeding irrespective of the level of renal impairment compared to VKAs. There was no difference in risk of intra-cranial bleeding between DOACs and VKAs.
Topics: Anticoagulants; Hemorrhage; Humans; Renal Insufficiency, Chronic; Venous Thromboembolism; Vitamin K
PubMed: 33310644
DOI: 10.1016/j.thromres.2020.11.036 -
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 -
Clinical Cardiology Jul 2021Several observational studies have compared the effectiveness and safety outcomes between nonvitamin K antagonist oral anticoagulants (NOACs) and vitamin K antagonists... (Meta-Analysis)
Meta-Analysis Review
Non-vitamin K antagonist oral anticoagulants versus vitamin K antagonists in atrial fibrillation patients with previous stroke or intracranial hemorrhage: A systematic review and meta-analysis of observational studies.
Several observational studies have compared the effectiveness and safety outcomes between nonvitamin K antagonist oral anticoagulants (NOACs) and vitamin K antagonists (VKAs) in atrial fibrillation (AF) patients with a history of either stroke/transient ischemic attack (TIA) or intracranial hemorrhage. Therefore, our current meta-analysis aimed to address this issue. The Cochrane Library, PubMed, and Embase databases were systematically searched until December 2020 for all relevant observational studies. We applied a random-effects model to pool adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for this meta-analysis. A total of 10 studies were included. Among patients with a history of stroke/TIA, the use of NOACs versus VKAs was associated with decreased risks of stroke (HR, 0.82, 95% CI 0.69-0.97), systemic embolism (HR, 0.73, 95% CI 0.61-0.87), all-cause death (HR, 0.87, 95% CI 0.81-0.94), major bleeding (HR, 0.77, 95% CI 0.64-0.92) and intracranial hemorrhage (HR, 0.54, 95% CI 0.38-0.77). Among patients with a history of intracranial hemorrhage, the use of NOACs versus VKAs was associated with reduced risks of stroke (HR, 0.81, 95% CI 0.68-0.95), all-cause death (HR, 0.68, 95% CI 0.49-0.94), and intracranial hemorrhage (HR, 0.66, 95% CI 0.51-0.84). Compared with VKAs, the use of NOACs exhibited superior efficacy and safety outcomes in AF patients with previous stroke/TIA, and the use of NOACs was associated with reduced risks of stroke, all-cause death, and intracranial hemorrhage in patients with a history of intracranial hemorrhage.
Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Intracranial Hemorrhages; Stroke; Vitamin K
PubMed: 34013988
DOI: 10.1002/clc.23647 -
The New Phytologist Mar 2021Understanding plant thermal tolerance is fundamental to predicting impacts of extreme temperature events that are increasing in frequency and intensity across the globe....
Understanding plant thermal tolerance is fundamental to predicting impacts of extreme temperature events that are increasing in frequency and intensity across the globe. Extremes, not averages, drive species evolution, determine survival and increase crop performance. To better prioritize agricultural and natural systems research, it is crucial to evaluate how researchers are assessing the capacity of plants to tolerate extreme events. We conducted a systematic review to determine how plant thermal tolerance research is distributed across wild and domesticated plants, growth forms and biomes, and to identify crucial knowledge gaps. Our review shows that most thermal tolerance research examines cold tolerance of cultivated species; c. 5% of articles consider both heat and cold tolerance. Plants of extreme environments are understudied, and techniques widely applied in cultivated systems are largely unused in natural systems. Lastly, we find that lack of standardized methods and metrics compromises the potential for mechanistic insight. Our review provides an entry point for those new to the methods used in plant thermal tolerance research and bridges often disparate ecological and agricultural perspectives for the more experienced. We present a considered agenda of thermal tolerance research priorities to stimulate efficient, reliable and repeatable research across the spectrum of plant thermal tolerance.
Topics: Climate Change; Cold Temperature; Ecosystem; Hot Temperature; Photosynthesis; Temperature
PubMed: 33124040
DOI: 10.1111/nph.17052 -
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 -
Blood Coagulation & Fibrinolysis : An... Oct 2022Thromboprophylaxis is the cornerstone strategy for thrombotic antiphospholipid syndrome (APS). Data comparing direct oral anticoagulants (DOACs) to Vitamin K antagonists... (Meta-Analysis)
Meta-Analysis
Comparing the efficacy and safety of direct oral anticoagulants versus Vitamin K antagonists in patients with antiphospholipid syndrome: a systematic review and meta-analysis.
Thromboprophylaxis is the cornerstone strategy for thrombotic antiphospholipid syndrome (APS). Data comparing direct oral anticoagulants (DOACs) to Vitamin K antagonists (VKAs) in the secondary prevention of thrombosis in APS patients remain contentious. We aim to review and analyse literature on the efficacy and safety of DOACs compared with VKAs in treating patients with APS. A literature search was performed from inception to 31 December 2021. Subgroups were analysed based on the risk stratification of APS profiles and different DOAC types. A total of nine studies with 1131 patients were included in the meta-analysis. High-risk APS patients (triple positive APS) who used DOACs displayed an increased risk of recurrent thrombosis [risk ratio = 3.65, 95% confidence interval (95% CI): 1.49-8.93; I2 = 29%, P = 0.005] compared with those taking VKAs. Similar risk of recurrent thrombosis or major bleeding was noted in low-risk APS patients (single or double antibody-positive) upon administering DOACs or VKAs. The utilization of Rivaroxaban was associated with a high risk of recurrent thromboses (RR = 2.63; 95% CI: 1.56-4.42; I2 = 0, P = 0.0003), particularly recurrent arterial thromboses (RR = 4.52; 95% CI: 1.99-10.29; I2 = 0, P = 0.18) in overall APS patients. Comparisons of the rate of recurrent thrombosis events and major bleeding events when using dabigatran or apixaban versus VKAs yielded no statistical differences. In the absence of contraindications, this meta-analysis suggests that VKAs remain the first-choice treatment for high-risk APS patients, with DOACs a more appropriate option for low-risk APS patients. Different DOACs may exhibit different levels of efficacy and safety for thromboprophylaxis in APS patients and require further exploration.
Topics: Administration, Oral; Anticoagulants; Antiphospholipid Syndrome; Dabigatran; Fibrinolytic Agents; Hemorrhage; Humans; Rivaroxaban; Thrombosis; Venous Thromboembolism; Vitamin K
PubMed: 35867933
DOI: 10.1097/MBC.0000000000001153 -
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 -
Critical Care Medicine May 2024Four-factor prothrombin complex concentrate (4-PCC) is recommended for rapid reversal of vitamin K antagonists (VKAs) such as warfarin, yet optimal dosing remains... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Four-factor prothrombin complex concentrate (4-PCC) is recommended for rapid reversal of vitamin K antagonists (VKAs) such as warfarin, yet optimal dosing remains uncertain.
DATA SOURCES
A systematic review was conducted of PubMed, Embase, and Ovid MEDLINE (Wolters Kluwer) databases from January 2000 to August 2023 for clinical studies comparing fixed- vs. variable-dose 4-PCC for emergent VKA reversal with at least one reported clinical outcome.
STUDY SELECTION
Abstracts and full texts were assessed independently and in duplicate by two reviewers.
DATA EXTRACTION
Data were extracted independently and in duplicate by two reviewers using predefined extraction forms.
DATA SYNTHESIS
The analysis comprised three randomized trials and 16 cohort studies comprising a total of 323 participants in randomized trials (161 in fixed dosage and 162 in variable dosage) and 1912 patients in cohort studies (858 in fixed-dose and 1054 in variable dose). Extracranial bleeding was the predominant indication, while intracranial hemorrhage varied. Overall, a fixed-dose regimen may be associated with a lower dose of 4-PCC and results in a reduction in 4-PCC administration time compared with a variable-dose regimen. A fixed-dose regimen also likely results in increased clinical hemostasis. While there is no clear difference between the two regimens in terms of achieving a goal international normalized ratio (INR) less than 2, a fixed-dose regimen is less likely to achieve a goal INR less than 1.5. High certainty evidence indicates that the fixed-dose regimen reduces both mortality and the occurrence of thromboembolic events. Additional subgroup analyses provides exploratory data to guide future studies.
CONCLUSIONS
A fixed-dose regimen for 4-PCC administration provides benefits over a variable-dose regimen in terms of dose reduction, faster administration time, improved clinical hemostasis, and reduced mortality and thromboembolic events. Further studies are warranted to better refine the optimal fixed-dose regimen.
Topics: Humans; Blood Coagulation Factors; Anticoagulants; Hemorrhage; Thromboembolism; International Normalized Ratio; Fibrinolytic Agents; Vitamin K; Retrospective Studies
PubMed: 38353592
DOI: 10.1097/CCM.0000000000006212 -
Journal of Neurology Dec 2019To obtain precise estimates of age, haematoma volume, secondary haematoma expansion (HE) and mortality for patients with intracerebral haemorrhage (ICH) taking oral... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To obtain precise estimates of age, haematoma volume, secondary haematoma expansion (HE) and mortality for patients with intracerebral haemorrhage (ICH) taking oral anticoagulants [Vitamin K antagonists (VKA-ICH) or non-Vitamin K antagonist oral anticoagulants (NOAC-ICH)] and those not taking oral anticoagulants (non-OAC ICH) at ICH symptom onset.
METHODS
We conducted a systematic review and meta-analysis of studies comparing VKA-ICH or NOAC-ICH or both with non-OAC ICH. Primary outcomes were haematoma volume (in ml), HE, and mortality (in-hospital and 3-month). We calculated odds ratios (ORs) using the Mantel-Haenszel random-effects method and corresponding 95% confidence intervals (95%CI) and determined the mean ICH volume difference.
RESULTS
We identified 19 studies including data from 16,546 patients with VKA-ICH and 128,561 patients with non-OAC ICH. Only 2 studies reported data on 4943 patients with NOAC-ICH. Patients with VKA-ICH were significantly older than patients with non-OAC ICH (mean age difference: 5.55 years, 95%CI 4.03-7.07, p < 0.0001, I = 92%, p < 0.001). Haematoma volume was significantly larger in VKA-ICH with a mean difference of 9.66 ml (95%CI 6.24-13.07 ml, p < 0.00001; I = 42%, p = 0.05). HE occurred significantly more often in VKA-ICH (OR 2.96, 95%CI 1.74-4.97, p < 0.00001; I = 65%). VKA-ICH was associated with significantly higher in-hospital mortality (VKA-ICH: 32.8% vs. non-OAC ICH: 22.4%; OR 1.83, 95%CI 1.61-2.07, p < 0.00001, I = 20%, p = 0.27) and 3-month mortality (VKA-ICH: 47.1% vs. non-OAC ICH: 25.5%; OR 2.24, 95%CI 1.52-3.31, p < 0.00001, I = 71%, p = 0.001). We did not find sufficient data for a meta-analysis comparing NOAC-ICH and non-OAC-ICH.
CONCLUSION
This meta-analysis confirms, refines and expands findings from prior studies. We provide precise estimates of key prognostic factors and outcomes for VKA-ICH, which has larger haematoma volume, increased rate of HE and higher mortality compared to non-OAC ICH. There are insufficient data on NOACs.
Topics: Anticoagulants; Cerebral Hemorrhage; Hematoma; Humans; Vitamin K
PubMed: 31541341
DOI: 10.1007/s00415-019-09536-1 -
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