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Journal of Thrombosis and Haemostasis :... 2014New direct oral anticoagulants (NOACs) constitute a novel treatment option for acute venous thromboembolism (VTE), with practical advantages. Individual studies have... (Meta-Analysis)
Meta-Analysis Review
Effectiveness and safety of novel oral anticoagulants as compared with vitamin K antagonists in the treatment of acute symptomatic venous thromboembolism: a systematic review and meta-analysis.
INTRODUCTION
New direct oral anticoagulants (NOACs) constitute a novel treatment option for acute venous thromboembolism (VTE), with practical advantages. Individual studies have demonstrated comparable efficacy to that of vitamin K antagonists (VKAs) and have suggested a more favorable safety profile . We performed a meta-analysis to determine the efficacy and safety of NOACs as compared with those of VKAs in patients with acute VTE.
METHODS
We searched MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews and the Clinical Trials Registry up to October 2013. Eligible studies included phase 3 trials comparing NOACs with VKAs in patients with acute VTE. Relative risks (RRs), absolute risk differences and numbers needed to treat (NNTs) to prevent one event were calculated for recurrent VTE, fatal pulmonary embolism (PE), overall mortality, major bleeding, and other bleeding complications, with random-effects models.
RESULTS
Five studies were included, investigating four NOACs (rivaroxaban, dabigatran, apixaban, and edoxaban) in 24 455 patients with acute VTE. RRs for recurrent VTE, fatal PE and overall mortality for NOACs vs. VKAs were 0.88 (95% confidence interval [CI] 0.74-1.05), 1.02 (95% CI 0.39-5.96), and 0.97 (95% CI 0.83-1.14), respectively. The RR for major bleeding was 0.60 (95% CI 0.41-0.88). The NNT with NOACs instead of VKA to prevent one major bleed was 149. The RR and NNT for fatal bleeding were 0.36 (95% CI 0.15-0.87) and 1111. A fixed-effect network analysis did not demonstrate significant differences between individual NOACs and rivaroxaban.
CONCLUSIONS
NOACs have comparable efficacy to that of VKAs, and are associated with a significantly lower risk of bleeding complications, although the NNT to prevent one major bleed was relatively high.
Topics: Administration, Oral; Anticoagulants; Benzimidazoles; Dabigatran; Female; Hemorrhage; Humans; Male; Morpholines; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Risk Factors; Rivaroxaban; Thiazoles; Thiophenes; Treatment Outcome; Venous Thromboembolism; Vitamin K; beta-Alanine
PubMed: 24330006
DOI: 10.1111/jth.12485 -
Blood Advances Mar 2019Patients receiving vitamin K antagonists (VKAs) with an international normalized ratio (INR) between 4.5 and 10 are at increased risk of bleeding. We systematically... (Meta-Analysis)
Meta-Analysis Review
Patients receiving vitamin K antagonists (VKAs) with an international normalized ratio (INR) between 4.5 and 10 are at increased risk of bleeding. We systematically reviewed the literature to evaluate the effectiveness and safety of administering vitamin K in patients receiving VKA therapy with INR between 4.5 and 10 and without bleeding. Medline, Embase, and Cochrane databases were searched for relevant randomized controlled trials in April 2018. Search strategy included terms vitamin K administration and VKA-related terms. Reference lists of relevant studies were reviewed, and experts in the field were contacted for relevant papers. Two investigators independently screened and collected data. Risk ratios (RRs) were calculated, and certainty of the evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation. Six studies (1074 participants) were included in the review and meta-analyses. Pooled estimates indicate a nonsignificant increased risk of mortality (RR = 1.42; 95% confidence interval [CI], 0.62-2.47), bleeding (RR = 2.24; 95% CI, 0.81-7.27), and thromboembolism (RR = 1.29; 95% CI, 0.35-4.78) for vitamin K administration, with moderate certainty of the evidence resulting from serious imprecision as CIs included potential for benefit and harm. Patients receiving vitamin K had a nonsignificant increase in the likelihood of reaching goal INR (1.95; 95% CI, 0.88-4.33), with very low certainty of the evidence resulting from serious risk of bias, inconsistency, and imprecision. Our findings indicate that patients on VKA therapy who have an INR between 4.5 and 10.0 without bleeding are not likely to benefit from vitamin K administration in addition to temporary VKA cessation.
Topics: Anticoagulants; Hemorrhage; Humans; International Normalized Ratio; Risk Assessment; Vitamin K; Vitamin K Deficiency
PubMed: 30850385
DOI: 10.1182/bloodadvances.2018025163 -
Journal of Interventional Cardiac... Mar 2023In patients with atrial fibrillation (AF) and stable ischemic heart disease, recent guidelines recommend oral anticoagulant (OAC) monotherapy in preference to... (Meta-Analysis)
Meta-Analysis
Dual therapy with oral anticoagulation and single antiplatelet agent versus monotherapy with oral anticoagulation alone in patients with atrial fibrillation and stable ischemic heart disease: a systematic review and meta-analysis.
BACKGROUND
In patients with atrial fibrillation (AF) and stable ischemic heart disease, recent guidelines recommend oral anticoagulant (OAC) monotherapy in preference to OAC + single antiplatelet agent (SAPT) dual therapy. However, these data are based on the results of only two randomized controlled trials (RCTs) and a relatively small group of patients. Thus, the safety and efficacy of this approach may be underpowered to detect a significant difference. We hypothesized that OAC monotherapy will have a reduced risk of bleeding, but similar all-cause mortality and ischemic outcomes as compared to dual therapy (OAC + SAPT).
METHODS
A systematic search of PubMed/MEDLINE, EMBASE, and Scopus was conducted. Safety outcomes included total bleeding, major bleeding, and others. Efficacy outcomes included all-cause mortality, cardiovascular mortality, myocardial infarction, stroke, and major adverse cardiovascular events (MACE). RCTs and observational studies were pooled separately (study design stratified meta-analysis). Subgroup analyses were performed for vitamin K antagonists and direct oral anticoagulants (DOACs). Pooled risk ratios (RR) with corresponding 95% confidence intervals (CI) were calculated using the Mantel-Haenszel method.
RESULTS
Meta-analysis of 2 RCTs comprising a total of 2905 patients showed that dual therapy (OAC + SAPT) vs. OAC monotherapy was associated with a statistically significant increase in major bleeding (RR 1.51; 95% CI [1.10, 2.06]). There was no significant reduction in MACE (RR 1.10; [0.71, 1.72]), stroke (RR 1.29; [0.85, 1.95]), myocardial infarction (RR 0.57; [0.28, 1.16]), cardiovascular mortality (RR 1.22; [0.63, 2.35]), or all-cause mortality (RR 1.18 [0.52, 2.68]). Meta-analysis of 20 observational studies comprising 47,451 patients showed that dual therapy (OAC + SAPT) vs. OAC monotherapy was associated with a statistically significant higher total bleeding (RR 1.50; [1.20, 1.88]), major bleeding (RR = 1.49; [1.38, 1.61]), gastrointestinal bleeding (RR = 1.62; [1.15, 2.28]), and myocardial infarction (RR = 1.15; [1.05, 1.26]), without significantly lower MACE (RR 1.10; [0.97, 1.24]), stroke (RR 0.93; [0.73, 1.19]), cardiovascular mortality (RR 1.11; [0.95, 1.29]), or all-cause mortality (RR 0.93; [0.78, 1.11]). Subgroup analysis showed similar results for both vitamin K antagonists and DOACs, except a statistically significant higher intracranial bleeding with vitamin K antagonist + SAPT vs. vitamin K antagonist monotherapy (RR 1.89; [1.36-2.63]).
CONCLUSIONS
In patients with AF and stable ischemic heart disease, OAC + SAPT as compared to OAC monotherapy is associated with a significant increase in bleeding events without a significant reduction in thrombotic events, cardiovascular mortality, and all-cause mortality.
Topics: Humans; Platelet Aggregation Inhibitors; Atrial Fibrillation; Treatment Outcome; Myocardial Ischemia; Anticoagulants; Hemorrhage; Stroke; Myocardial Infarction; Fibrinolytic Agents; Vitamin K; Administration, Oral
PubMed: 36085242
DOI: 10.1007/s10840-022-01347-1 -
Vitamin K antagonist reversal strategies: Systematic review and network meta-analysis from the AABB.Transfusion Aug 2022Anticoagulation requires urgent reversal in cases of life-threatening bleeding or invasive procedures. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Anticoagulation requires urgent reversal in cases of life-threatening bleeding or invasive procedures.
STUDY DESIGN AND METHODS
Network meta-analysis for comparing the safety and efficacy of warfarin reversal strategies including plasma and prothrombin complex concentrates (PCCs).
RESULTS
Seven studies including 594 subjects using reversal agents plasma, 3-factor-PCC (Uman Complex and Konyne), and 4-factor-PCC (Beriplex/KCentra, Octaplex, and Cofact) met inclusion criteria. Compared with plasma, patients receiving Cofact probably have a higher rate of international normalized ratio (INR) correction (risk difference [RD] 499 more per 1000 patients, 95% confidence interval [CI], 176-761, low certainty[LC]); higher reversal of bleeding (323 more per 1000 patients, 11-344 more, LC); and fewer transfusion requirements (0.96 fewer units, 1.65-0.27 fewer, LC). Patients receiving Beriplex/KCentra probably have a higher rate of INR correction (476 more per 1000 patients, 332-609 more, LC); higher reversal of bleeding (127 more per 1000 patients, 43 fewer to 236 more); and similar transfusion requirements (0.01 fewer units, 0.31 fewer to 0.28 more, high/moderate certainty). Patients receiving Octaplex probably have a higher rate of INR correction (RD 579 more per 1000 patients, 189-825 more, LC).
CONCLUSIONS
PCCs probably provide an advantage in INR reversal compared to plasma. There was no added risk of adverse events with PCCs.
Topics: Anticoagulants; Blood Coagulation Factors; Factor IX; Factor X; Fibrinolytic Agents; Hemorrhage; Humans; International Normalized Ratio; Network Meta-Analysis; Prothrombin; Retrospective Studies; Vitamin K; Warfarin
PubMed: 35834523
DOI: 10.1111/trf.17010 -
Cardiovascular Drugs and Therapy Jun 2022The optimal dosing strategy of four-factor prothrombin complex concentrate (4F-PCC) for vitamin K antagonists (VKAs) reversal is unknown. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The optimal dosing strategy of four-factor prothrombin complex concentrate (4F-PCC) for vitamin K antagonists (VKAs) reversal is unknown.
METHODS
We conducted systematic search on the PubMed, SCOPUS, and Embase databases from inception to December 2020 for clinical studies that compared the fixed-dose versus variable-dose of 4-PCC for VKAs reversal with at least one reported clinical outcome. The treatment effects were expressed as relative ratios (RR) with 95% confidence intervals (CIs) and pooled by a random-effects model.
RESULTS
Ten studies, including 988 patients, were included. Fixed-dose 4-PCC was associated with lower rate of mortality (RR= 0.65, 95% CI 0.47 to 0.9, p= 0.009), comparable rate of thromboembolic event (TEE) (RR= 1.10, 95%CI 0.44 to 2.80, p= 0.826), and lower goal INR reached (RR= 0.87, 95%CI 0.78 to 0.96, p= 0.007). Less 4-PCC cumulative dose, shorter duration of order-to-needle time, similar hospital length of stay, the comparable time required for INR reversal, higher post-4-PCC INR, and a higher need for additional dose were observed in fixed-dose.
CONCLUSIONS
The use of a fixed-dose of 4-PCC may be considered an effective and safe dosing strategy for VKAs reversal in various clinical situations. However, further well-designed, controlled studies should be conducted focusing on clinical outcomes to determine the optimal dose of 4-PCC for VKAs reversal.
Topics: Anticoagulants; Fibrinolytic Agents; Humans; International Normalized Ratio; Retrospective Studies; Thromboembolism; Vitamin K
PubMed: 33864534
DOI: 10.1007/s10557-021-07192-0 -
Chest Jun 2019The efficacy and safety of direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) during extended anticoagulation for a VTE remains largely unknown,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The efficacy and safety of direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) during extended anticoagulation for a VTE remains largely unknown, especially in terms of potential survival benefit. The goal of this study was to assess the effects of VKAs and DOACs on overall mortality and VTE-related mortality, as well as VTE recurrence and safety.
METHODS
PubMed, EMBASE, and the Cochrane Library were searched from January 1990 through September 2018 for randomized controlled trials evaluating the effect of extended anticoagulants as secondary prevention for VTE compared with placebo. The primary outcome was the specific effects of standard-intensity VKAs and DOACs on overall mortality.
RESULTS
Sixteen studies (12,458 patients) were included. DOACs were associated with a reduction in overall (risk ratio [RR], 0.48; 95% CI, 0.27-0.86; P = .01) and VTE-related (RR, 0.36; 95% CI, 0.15-0.89; P = .03) mortality, whereas VKAs were not (P > .50). Although VKAs and DOACs similarly prevented recurrent VTE, only VKAs were associated with an increased risk of major bleeding (RR, 2.67; 95% CI, 1.28-5.60; P < .01), resulting in an improved net clinical benefit for DOACs (RR, 0.25 [95% CI, 0.16-0.39; P < .01] vs 0.46 [95% CI, 0.30-0.72; P < .01]; P = .05).
CONCLUSIONS
DOACs for extended anticoagulation were associated with a significant reduction in overall mortality compared with observation alone.
TRIAL REGISTRY
PROSPERO; No.: CRD42018088739; URL: https://www.crd.york.ac.uk/prospero/.
Topics: Anticoagulants; Factor Xa Inhibitors; Humans; Risk Assessment; Secondary Prevention; Survival Analysis; Treatment Outcome; Venous Thromboembolism; Vitamin K
PubMed: 31174635
DOI: 10.1016/j.chest.2019.02.402 -
Clinical Drug Investigation Nov 2021Real-life data about the use of dabigatran in patients with non-valvular atrial fibrillation are warranted. The objective of this systematic review and meta-analysis was... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVE
Real-life data about the use of dabigatran in patients with non-valvular atrial fibrillation are warranted. The objective of this systematic review and meta-analysis was to assess the effectiveness and safety of dabigatran, globally and stratified by dose (110/150 mg twice daily), vs vitamin K antagonists in non-Asian patients with non-valvular atrial fibrillation from "real-world" studies.
METHODS
A systematic review was performed according to Cochrane methodological standards. The results were reported according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses Statement) statement. The ROBINS-I tool was used to assess bias risk. MEDLINE and EMBASE, from inception up to May 2021, using appropriate controlled vocabulary and free search terms, were searched. RESULTS: A total of 34 studies, corresponding to 37 articles involving 1,600,722 participants (1,154,283 exposed to vitamin K antagonists and 446,439 to dabigatran) were eligible for this review. Dabigatran 150 mg reduced the risk of ischemic stroke compared with vitamin K antagonists, with a 14% risk reduction (hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.74-0.98). Globally, dabigatran reduced the risk of all-cause mortality compared with vitamin K antagonists (HR 0.76, 95% CI 0.69-0.84), with a greater effect observed with dabigatran 150 mg (HR 0.65, 95% CI 0.58-0.73). There was a trend towards a lower risk of myocardial infarction with dabigatran 150 mg (HR 0.86, 95% CI 0.71-1.04). Regarding the primary safety outcomes, dabigatran (either at a dose of 150 mg or 110 mg) reduced the risk of major bleeding compared with vitamin K antagonists (HR 0.77, 95% CI 0.70-0.83), as well as the risk of intracranial bleeding (HR 0.44, 95% CI 0.39-0.50) and fatal bleeding (HR 0.76, 95% CI 0.60-0.95), but with a slight increase in gastrointestinal bleeding risk (HR 1.16, 95% CI 1.08-1.26).
CONCLUSIONS
Dabigatran has a favorable impact on effectiveness and safety outcomes compared with vitamin K antagonists in real-world populations.
Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Dabigatran; Humans; Rivaroxaban; Stroke; Vitamin K
PubMed: 34643934
DOI: 10.1007/s40261-021-01091-w -
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 -
Clinical Nutrition ESPEN Oct 2022Rheumatoid arthritis (RA) is an autoimmune disease of multifactorial etiology, characterized by a chronic inflammatory reaction of the joints, but can also affect other... (Review)
Review
Rheumatoid arthritis (RA) is an autoimmune disease of multifactorial etiology, characterized by a chronic inflammatory reaction of the joints, but can also affect other tissues. Some environmental factors can trigger an immune system response in genetically susceptible individuals, activating the disease. Lower diversity of gut microbiota, and dysbiosis, have been observed in RA patients. In this regard, approaches to decrease inflammation, and to restore the microbiota, have been suggested. These include oral administration of single probiotics, or probiotic mixtures, on their own, or in combination with drugs. Vitamin K (VitK) is one of the many products of the intestinal microbiota. Lower levels of some forms of VitK have been measured in the serum and stools of RA patients and some studies have found an inverse correlation between VitK levels and the clinical severity of the disease. Additionally, some forms of this vitamin, when given orally, have been shown to exert positive effects in decreasing RA activity, and delaying its onset and progress. This review aims at describing the link between the gut microbiota and RA, focusing on the role of VitK and probiotics as possible adjuvant therapies in this disease.
Topics: Arthritis, Rheumatoid; Gastrointestinal Microbiome; Humans; Inflammation; Probiotics; Rheumatic Fever; Vitamin K; Vitamins
PubMed: 36184230
DOI: 10.1016/j.clnesp.2022.08.002 -
Pharmacotherapy Nov 2013Difficulties managing warfarin therapy have led to speculation that daily supplementation with a low dose of vitamin K might improve anticoagulation control and clinical... (Meta-Analysis)
Meta-Analysis Review
Anticoagulation control with daily low-dose vitamin k to reduce clinically adverse outcomes and international normalized ratio variability: a systematic review and meta-analysis.
STUDY OBJECTIVES
Difficulties managing warfarin therapy have led to speculation that daily supplementation with a low dose of vitamin K might improve anticoagulation control and clinical outcomes. Thus we sought to review the available medical literature systematically examining the effectiveness of low-dose vitamin K supplementation for the reduction of clinically relevant adverse events due to vitamin K antagonist (VKA) use and for stabilization of the international normalized ratio (INR).
DESIGN
We searched the Medline and Embase databases, the Cochrane Library, International Pharmaceutical Abstracts, and the U.S. National Institutes of Health clinical trials registry for randomized controlled trials of vitamin K supplementation versus placebo in patients receiving a VKA. We evaluated the outcomes of hemorrhage, thromboembolic events, and percentage of time in therapeutic range (TTR) of INRs by using the Grading of Recommendations Assessment, Development and Evaluation system for rating quality of evidence in the abstracted studies.
SETTING
All randomized controlled trials studies published between 1970 and August 2012 which fitted our search strategy.
PATIENTS
Patients over the age of 18 years on VKA therapy.
RESULTS
Of the 624 studies we identified and screened, three studies (626 patients) were included in the meta-analysis. Most of the patients had a satisfactory TTR at baseline. We found low-quality evidence--downgraded for imprecision and risk of bias (i.e., limitation in study design and/or execution)--of no effect of vitamin K use (100 to 200 μg) on hemorrhagic events (relative risk [RR] 3.2, 95% confidence interval [CI] 0.2-64.2) and thromboembolic events (RR 2.2, 95% CI 0.1-47.5) and a significant but clinically unimportant effect on TTR with an absolute increase of 3.5% (95% CI 1.1-6.0).
CONCLUSION
This meta-analysis, despite the few studies and overall low quality, suggests no beneficial role of low-dose (100 to 200 μg) vitamin K supplementation on the reduction of clinically relevant adverse events in patients taking VKAs, despite a small improvement of the TTR. Data were insufficient, however, from patients with unstable INRs.
Topics: Anticoagulants; Blood Coagulation; Dietary Supplements; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; International Normalized Ratio; Randomized Controlled Trials as Topic; Treatment Outcome; Vitamin K
PubMed: 23744743
DOI: 10.1002/phar.1302