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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 -
Clinical Pharmacology and Therapeutics Aug 2022Available data have shown an association between direct oral anticoagulant (DOAC) plasma concentration and clinical, particularly bleeding, events. Factors that may...
Available data have shown an association between direct oral anticoagulant (DOAC) plasma concentration and clinical, particularly bleeding, events. Factors that may influence DOAC plasma concentration are therefore the focus of particular attention. Population pharmacokinetic (PopPK) analyses can help in identifying such factors while providing predictive models. The main aim of the present study was to identify all the PopPK models to date for the four most frequently used DOACs (dabigatran, apixaban, rivaroxaban, and edoxaban). The secondary aim was to use these models to simulate different DOAC plasma concentration-time profiles in relevant clinical scenarios. The results of our model-based simulations confirm the clinical relevance of the known major factors influencing DOAC exposure and support the current approved dose adaptation, at least for atrial fibrillation. They also highlight how the accumulation of covariates, not currently considered for dose adaptation due to their seemingly minor influence on DOAC exposure, lead to supratherapeutic blood concentrations and could thus enhance the risk of major bleeding. The present results therefore question DOAC dose adaptation in the presence of these covariates, such as drug-drug interaction or genotypes, alongside the known existing covariates. As the overall effect of accumulation of several covariates could be difficult to apprehend for the clinicians, PopPK modeling could represent an interesting approach for informed precision dosing and to improve personalized prescription of DOACs.
Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Dabigatran; Hemorrhage; Humans; Pyridones; Rivaroxaban; Stroke
PubMed: 35593020
DOI: 10.1002/cpt.2649 -
BMC Cardiovascular Disorders Mar 2022The real-world studies on recurrent venous thromboembolism (VTE) and bleeding events of non-vitamin K antagonist oral anticoagulants (NOACs) in VTE patients have... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The real-world studies on recurrent venous thromboembolism (VTE) and bleeding events of non-vitamin K antagonist oral anticoagulants (NOACs) in VTE patients have reported conflicting findings. Our study aimed to provide the direct comparison evidence of different NOACs for VTE patients in clinical practice settings.
METHODS
Search of the medical literature was conducted using PubMed, Web of Science, EMBASE, Clinical Trials.gov, and the Cochrane Library from inception to March 22, 2021. Among the 19,996 citations retrieved, a total of 63,144 patients from 6 studies were analyzed. Clinical outcomes included recurrent VTE, death, and different bleeding events.
RESULTS
Adjusted hazard ratio (HR) analysis suggested that apixaban had significant lower bleeding riskthan rivaroxaban (major, minor and any bleeding: HR = 0.61, 0.56, 0.70; p = 0.008, < 0.0001, 0.006, respectively), but no statistics difference found in recurrent VTE events (HR = 1.02, 95% confidence interval (CI) 0.71-1.47, p = 0.93). There was no significant difference of major bleeding between dabigatran and rivaroxaban (odds ratios (OR) = 0.41, 95% CI 0.09-1.90, p = 0.25), apixaban and dabigatran (OR 0.64, 95% CI 0.15-2.72, p = 0.83). No significant difference was found in the comparison of edoxaban and other NOACs in VTE recurrence, major bleeding and composite outcome.
CONCLUSIONS
In the prevention of bleeding events, apixaban was associated with a lower risk than rivaroxaban, but equivalent efficacy for different NOACs in prevention of recurrent VTE. Evidence generated from the meta-analysis based on real-world data can help to guide selection between apixaban and rivaroxaban in routine clinical practice.
TRIAL REGISTRATION
This systematic review and meta-analysis were conducted and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis and Meta-analysis of Observational Studies in Epidemiology statements and was registered with PROSPERO (CRD42019140553).
Topics: Administration, Oral; Anticoagulants; Dabigatran; Hemorrhage; Humans; Rivaroxaban; Venous Thromboembolism
PubMed: 35287588
DOI: 10.1186/s12872-022-02550-8 -
Value in Health : the Journal of the... Mar 2022This study aimed to examine the extent and quality of evidence from economic evaluations (EEs) of genetic-guided pharmacotherapy (PGx) for atrial fibrillation (AF) and...
OBJECTIVES
This study aimed to examine the extent and quality of evidence from economic evaluations (EEs) of genetic-guided pharmacotherapy (PGx) for atrial fibrillation (AF) and to identify variables influential in changing base-case conclusions.
METHODS
From systematic searches, we included EEs of existing PGx testing to guide pharmacotherapy for AF, without restrictions on population characteristics or language. Articles excluded were genetic tests used to guide device-based therapy or focused on animals.
RESULTS
We found 18 EEs (46 comparisons), all model-based cost-utility analysis with or without cost-effectiveness analysis mostly from health system's perspectives, of PGx testing to determine coumadin/direct-acting anticoagulant (DOAC) dosing (14 of 18), to stratify patients into coumadin/DOACs (3 of 18), or to increase patients' adherence to coumadin (1 of 18) versus non-PGx. Most PGx to determine coumadin dosing found PGx more costly and more effective than standard or clinical coumadin dosing (19 of 24 comparisons) but less costly and less effective than standard DOAC dosing (14 of 14 comparisons). The remaining comparisons were too few to observe any trend. Of 61 variables influential in changing base-case conclusions, effectiveness of PGx testing was the most common (37%), accounted for in the models using time-based or medication-based approaches or relative risk. The cost of PGx testing has decreased and plateaued over time.
CONCLUSIONS
EEs to date only partially inform decisions on selecting optimal PGx testing for AF, because most evidence focuses on PGx testing to determine coumadin dosing, but less on other purposes. Future EE may refer to the list of influential variables and the approaches used to account for the effect of PGx testing to inform data collection and study design.
Topics: Anticoagulants; Atrial Fibrillation; Cost-Benefit Analysis; Factor Xa Inhibitors; Humans; Models, Statistical; Pharmacogenetics; Quality-Adjusted Life Years; Warfarin
PubMed: 35227459
DOI: 10.1016/j.jval.2021.09.013 -
F1000Research 2021An earlier systematic review reported no differences in the incidence of recurrent venous thromboembolism and major bleeding between factor Xa inhibitors and standard... (Meta-Analysis)
Meta-Analysis
An earlier systematic review reported no differences in the incidence of recurrent venous thromboembolism and major bleeding between factor Xa inhibitors and standard anticoagulation. The present meta-analysis aimed to assess the effectiveness of factor Xa inhibitors for the management of venous thromboembolism (VTE), specifically in patients with cancer, as there were more randomized clinical trials (RCTs) available. The PubMed and Cochrane Library databases were systematically screened for all RCTs assessing factor Xa inhibitor efficacy for VTE management in cancer patients. Using RevMan 5.3, we performed a Mantel-Haenszel fixed-effects meta-analysis of the following outcomes: recurrent VTE, VTE events, and major bleeding rates. We identified 11 studies involving 7,965 patients. Factor Xa inhibitors were superior in preventing VTE recurrence, compared to low-molecular-weight heparin (LMWH) (OR 0.60; 95% CI 0.45-0.80; P < 0.01) and vitamin K antagonists (VKA) (OR 0.51; 95% CI 0.33-0.78; P < 0.01). As prophylaxis, factor Xa inhibitors had a similar rate of VTE compared to VKAs (OR 1.08 [95% CI 0.31-3.77]; P = 0.90) and a lower rate compared to placebo (OR 0.54 [95% CI 0.35-0.81]; P < 0.01). Major bleeding rates were higher with factor Xa inhibitors than with LMWHs (OR 1.34 [95% CI 0.83-2.18]; P = 0.23), but significantly lower than VKAs (OR 0.71 [95% CI 0.55-0.92]; P < 0.01). Factor Xa inhibitors are effective for VTE management in patients with cancer; however, they are also associated with an increased bleeding risk compared to LMWH, but decreased when compared to VKA.
Topics: Anticoagulants; Factor Xa Inhibitors; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Venous Thromboembolism
PubMed: 35136585
DOI: 10.12688/f1000research.73883.1 -
Cardiovascular Intervention and... Oct 2022Left atrial appendage closure (LAAC) are emerging treatment for patients with atrial fibrillation (AF). However, data on the safety, efficacy, and medications for LAAC... (Meta-Analysis)
Meta-Analysis
Latest outcomes of transcatheter left atrial appendage closure devices and direct oral anticoagulant therapy in patients with atrial fibrillation over the past 5 years: a systematic review and meta-analysis.
Left atrial appendage closure (LAAC) are emerging treatment for patients with atrial fibrillation (AF). However, data on the safety, efficacy, and medications for LAAC devices in patients with AF are lacking. We aimed to investigate the incidence of all-cause mortality, stroke, and major bleeding in AF patients with LAAC devices and DOACs. Moreover, we aimed to investigate the incidence rate of device-related thrombus (DRT) and the medications used in the management of AF patients with LAAC devices to gain insights into achieving better outcome. Based on a literature search using PubMed, EMBASE, Cochrane Library, and Web of Science databases between January 2015 and December 2020, eight LAAC device studies that used WATCHMAN and Amulet, and three DOAC studies that used rivaroxaban, with a total of 24,055 AF patients (LAAC devices, n = 2855; DOAC, n = 21,200), were included. A random-effects model was used to incorporate heterogeneity among studies. The pooled incidence of events per person-years were as follows: all-cause mortality, 0.06 (95% confidence interval [CI] 0.02-0.10) for WATCHMAN, 0.04 (95% CI 0.00-0.14) for Amulet, and 0.03 (95% CI 0.01-0.04) for rivaroxaban; stroke; 0.02 (95% CI 0.00-0.04) for WATCHMAN, 0 for Amulet, and 0.01 (95% CI 0.01-0.02) for rivaroxaban; major bleeding, 0.04 (95% CI 0.02-0.06) for WATCHMAN, 0.02 (95% CI 0.00-0.06) for Amulet, and 0.02 (95% CI 0.01-0.03) for rivaroxaban. The incidence rate of DRT was 2.3%, and complications were reported in 9%. The incidence of all-cause mortality, stroke, and major bleeding were similar between LAAC devices and DOACs. The rate of complications was acceptable, and those of DRT were lower than the average incidence reported in previous studies. However, further follow-up is needed. Concomitant anticoagulant and antiplatelet therapies should be further evaluated to find the optimal regimen for AF patients with LAAC devices.
Topics: Anticoagulants; Atrial Appendage; Atrial Fibrillation; Hemorrhage; Humans; Rivaroxaban; Stroke; Thrombosis; Treatment Outcome
PubMed: 35098478
DOI: 10.1007/s12928-022-00839-1 -
Thrombosis Research Feb 2022Anticoagulation is important for extracorporeal membrane oxygenation (ECMO). Heparin is widely used; however, in some cases, it is not suitable for patients. Bivalirudin... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Anticoagulation is important for extracorporeal membrane oxygenation (ECMO). Heparin is widely used; however, in some cases, it is not suitable for patients. Bivalirudin has been recently proposed for ECMO patients, and there is no evidence regarding its effectiveness and safety.
OBJECTIVE
We aimed to systematically review the effectiveness and safety of bivalirudin in ECMO patients.
STUDY DESIGN AND METHODS
PubMed, Web of Science, Cochrane Library, and EMBASE were searched to find relevant research on the use of bivalirudin versus heparin for anticoagulation in ECMO patients. Outcomes included in-hospital mortality, ECMO duration, major bleeding events, thrombosis events and circuit intervention events. Types of studies included randomized control trials (RCTs), cohort studies, and case-control studies. Case reports, studies lacking comparison with heparin, and where patients transitioned between heparin and bivalirudin, were excluded. Publication bias was evaluated when the number of included studies was more than ten. Sensitivity analysis was performed to examine the stability of the results.
RESULTS
Ten articles were selected, and nine articles were included in the meta-analysis. The results of the meta-analysis showed hospital mortality [OR = 0.65, 95%CI (0.44, 0.95), P = 0.03] and thrombosis events decreased (OR = 0.55, 95%CI [0.37, 0.83], P = 0.004) in bivalirudin group compared with heparin in adult patients. Major bleeding events (OR = 0.66, 95%CI [0.17, 2.55], P = 0.55), ECMO duration (MD = 18.92, 95%CI [-29.33, 67.17], P = 0.44) and circuit intervention events (OR = 1.67, 95%CI [0.54, 5.18], P = 0.37) in the bivalirudin group was not statistically significant compared with the heparin group.
CONCLUSION
Bivalirudin may provide survival benefits and reduce thrombosis in adult patients on ECMO compared with heparin. There is no difference in treating major bleeding events between bivalirudin and heparin group. However, because all included studies were retrospective observational studies, the evidence level of this systematic review is low and heterogeneity could not be avoided. More high-quality clinical studies are urgently needed to confirm these benefits.
Topics: Adult; Anticoagulants; Extracorporeal Membrane Oxygenation; Heparin; Hirudins; Humans; Peptide Fragments; Recombinant Proteins
PubMed: 35007937
DOI: 10.1016/j.thromres.2021.12.024 -
European Journal of Clinical... Apr 2022This study aimed to estimate the prevalence, contributory factors, and severity of medication errors associated with direct acting oral anticoagulants (DOACs). (Meta-Analysis)
Meta-Analysis
Prevalence, contributory factors and severity of medication errors associated with direct-acting oral anticoagulants in adult patients: a systematic review and meta-analysis.
PURPOSE
This study aimed to estimate the prevalence, contributory factors, and severity of medication errors associated with direct acting oral anticoagulants (DOACs).
METHODS
A systematic review and meta-analysis were undertaken by searching 11 databases including Medline, Embase, and CINHAL between January 2008 and September 2020. The pooled prevalence of errors and predictive intervals were estimated using random-effects models using Stata software. Data related to error causation were synthesised according to Reason's accident causation model.
RESULTS
From the 5205 titles screened, 32 studies were included which were mostly based in hospitals and included DOAC treatment for thromboembolism and atrial fibrillation. The proportion of study population who experienced either prescription, administration, or dispensing error ranged from 5.3 to 37.3%. The pooled percentage of patients experiencing prescribing error was 20% (95% CI 15-25%; I = 96%; 95% PrI 4-43%). Prescribing error constituted the majority of all error types with a pooled estimate of 78% (95%CI 73-82%; I = 0) of all errors. The common reported causes were active failures including wrong drug, and dose for the indication. Mistakes such as non-consideration of renal function, and error-provoking conditions such as lack of knowledge were common contributing factors. Adverse events such as potentially fatal intracranial haemorrhage or patient deaths were linked to the errors but causality assessments were often missing.
CONCLUSIONS
Despite their favourable safety profile, DOAC medication errors are common. There is a need to promote multidisciplinary working, guideline-adherence, training, and education of healthcare professionals, and the use of theory-based and technology-facilitated interventions to minimise errors and maximise the benefits of DOACs usage in all settings.
PROTOCOL
A protocol developed as per PRISMA-P guideline is registered under PROSPERO ID = CRD42019122996.
Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Factor Xa Inhibitors; Humans; Medication Errors
PubMed: 34935068
DOI: 10.1007/s00228-021-03212-y -
Blood Advances Jan 2022Idiopathic purpura fulminans (IPF) is a rare but severe prothrombotic coagulation disorder that can occur after chickenpox or human herpesvirus 6 (HHV-6) infection. IPF...
Idiopathic purpura fulminans (IPF) is a rare but severe prothrombotic coagulation disorder that can occur after chickenpox or human herpesvirus 6 (HHV-6) infection. IPF leads to an autoantibody-mediated decrease in the plasma concentration of protein S. We conducted a retrospective multicenter study involving patients with IPF from 13 French pediatric centers and a systematic review of cases in published literature. Eighteen patients were included in our case series, and 34 patients were included as literature review cases. The median age was 4.9 years, and the diagnostic delay after the first signs of viral infection was 7 days. The lower limbs were involved in 49 patients (94%) with typical lesions. In all, 41 patients (78%) had a recent history of varicella-zoster virus infection, and 7 patients (14%) had been infected by HHV-6. Most of the patients received heparin (n = 51; 98%) and fresh frozen plasma transfusions (n = 41; 79%); other treatment options were immunoglobulin infusion, platelet transfusion, corticosteroid therapy, plasmapheresis, and coagulation regulator concentrate infusion. The antithrombin level and platelet count at diagnosis seemed to be associated with severe complications. Given the rarity of this disease, the creation of a prospective international registry is required to consolidate these findings.
Topics: Child; Child, Preschool; Humans; Chickenpox; Delayed Diagnosis; Prospective Studies; Protein S; Purpura Fulminans; Retrospective Studies
PubMed: 34788405
DOI: 10.1182/bloodadvances.2021005126 -
European Review For Medical and... Oct 2021Total knee and hip arthroplasty are one of the most commonly consistently successful surgeries in orthopedics worldwide. Literature has reported that depending upon the... (Comparative Study)
Comparative Study Meta-Analysis
Comparison between use of direct oral anticoagulants and aspirin for risk of thromboembolism complications in patients undergoing total knee and hip arthroplasty: a systematic review and meta-analysis.
OBJECTIVE
Total knee and hip arthroplasty are one of the most commonly consistently successful surgeries in orthopedics worldwide. Literature has reported that depending upon the age and co-existing treatments, patients undergoing total knee and hip arthroplasty are often prone to increased risks of developing venous thromboembolic complications. In such cases, chemoprophylaxis with either direct oral anticoagulant therapy with factor-Xa inhibitors (i.e., rivaroxaban, apixaban, dabigatran) and aspirin are widely recommended. Recent surveys suggest that direct oral anticoagulants and aspirin have comparable efficacy. However, there is no consensus in the literature as to which drug is the safest. Therefore, in this review, we shall attempt to evaluate the comparative efficacy between direct oral anticoagulant drugs and aspirin in patients undergoing total joint arthroplasty. To compare risk of venous thromboembolism complications between use of direct oral anticoagulant drugs and aspirin in patients undergoing total knee and hip arthroplasty.
MATERIALS AND METHODS
A sensitive and specific analysis of the literature was performed according to the Cochrane and written according to PRISMA guidelines (Supplementary Table I). Five electronic databases (Web of Science, Embase, CENTRAL, Scopus, and Medline) were evaluated. To compare the efficacy between the drugs we conducted a random-effect meta-analysis according to the outcome (bleeding complications, venous thromboembolism or pulmonary embolism) and overall mortality in patients undergoing total knee and hip arthroplasty.
RESULTS
Overall, 993 studies were found of which 117 had their full texts evaluated. A total of 161,463 patients undergoing total joint arthroplasty with mean age equal 66.2 ± 5.0 years were identified in 14 studies. Higher risks of venous thromboembolism (OR: 1.56 95% CI 1.21-2.01), pulmonary embolism (OR: 1.63, 95% CI: 1.31 -2.04) and overall mortality (OR: 1.35, 95% CI 1.04-1.74) for patients receiving aspirin were verified as compared to direct oral anticoagulant drugs. Subsequently, we further observed that the risks of bleeding complications (OR: 0.89 95% CI 0.67-1.18) were insignificant.
CONCLUSIONS
The study reports higher risks of venous thromboembolism, pulmonary embolism, and overall mortality for the patients receiving aspirin before undergoing.
Topics: Aged; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Aspirin; Factor Xa Inhibitors; Hemorrhage; Humans; Middle Aged; Platelet Aggregation Inhibitors; Postoperative Complications; Pulmonary Embolism; Venous Thromboembolism
PubMed: 34730204
DOI: 10.26355/eurrev_202110_26994