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Heart (British Cardiac Society) Jun 2019Vascular stiffness (VS) and vascular calcification (VC) are surrogate markers of vascular health associated with cardiovascular events. Vitamin K-dependent proteins... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Vascular stiffness (VS) and vascular calcification (VC) are surrogate markers of vascular health associated with cardiovascular events. Vitamin K-dependent proteins (VKDP) are associated with VS and VC and require vitamin K for activity. We conducted a systematic review and meta-analysis of: (1) the effect of vitamin K supplementation on VS and VC and (2) association of inactive VKDP levels with incident cardiovascular disease and mortality.
METHODS
Two authors searched MEDLINE and Embase databases and Cochrane and ISRCTN registries for studies of vitamin K clinical trials that measured effects on VC, VS or VKDP and longitudinal studies assessing effect of VKDP on incident CVD or mortality. Random effects meta-analyses were performed.
RESULTS
Thirteen controlled clinical trials (n=2162) and 14 longitudinal studies (n=10 726) met prespecified inclusion criteria. Vitamin K supplementation was associated with significant reduction in VC (-9.1% (95% CI -17.7 to -0.5); p=0.04) and VKDP (desphospho-uncarboxylated matrix Gla protein; -44.7% (95% CI -65.1 to -24.3), p<0.0001) and uncarboxylated osteocalcin; -12.0% (95% CI -16.7 to -7.2), p<0.0001) compared with control, with a non-significant improvement in VS. In longitudinal studies with median follow-up of 7.8 (IQR 4.9-11.3) years, VKDP levels were associated with a combined endpoint of CVD or mortality (HR 0.45 (95% CI 0.07 to 0.83), p=0.02).
CONCLUSIONS
Supplementation with vitamin K significantly reduced VC, but not VS, compared with control. The conclusions drawn are limited by small numbers of studies with substantial heterogeneity. VKDP was associated with combined endpoint of CVD or mortality. Larger clinical trials of effect of vitamin K supplementation to improve VC, VS and long-term cardiovascular health are warranted.
TRIAL REGISTRATION NUMBER
CRD42017060344.
Topics: Biomarkers; Dietary Supplements; Humans; Vascular Calcification; Vascular Diseases; Vitamin K; Vitamins
PubMed: 30514729
DOI: 10.1136/heartjnl-2018-313955 -
Frontiers in Pharmacology 2022In recent years, many studies have found that vitamin K is beneficial to wound healing. However, some research results seem to be in conflict. The purpose of this study... (Review)
Review
In recent years, many studies have found that vitamin K is beneficial to wound healing. However, some research results seem to be in conflict. The purpose of this study was to evaluate the effect of vitamin K on wound healing. We systematically and comprehensively searched the PubMed, Web of Science, Embase, Cochrane library, China National Knowledge Infrastructure (CNKI), VIP and Wanfang eletronic databases. We applied revman5.3 software to calculate the weighted mean difference (WMD) of 95% confidence interval (CI) of animal and cell groups to evaluate the effect of vitamin K on wound healing. Two researchers independently selected studies and used the Cochrane Collaboration tool to assess the risk of bias in the included studies. The overall quality of evidence was assessed using the Recommendation, Assessment, Development and Evaluation (GRADE) working group approch. Among the 1081 articles searched, 6 articles (16 studies in total) met the inclusion criteria. The results of quantitative analysis showed that vitamin K was beneficial to increase the wound healing rate in animal models [rat model: WMD = 27.45 (95% CI: 13.46, 41.44); = 0.0001], but the opposite result was obtained in cell experiments [WMD = -33.84 (95% CI: -56.90, -10.79); = 0.004]. This meta-analysis hits that vitamin K could affect the process of wound healing, especially in animal models. While we could not know the clear role at present, which requires larger scale research. In addition, the concentration and safe dose of vitamin K also deserve further study.
PubMed: 36532748
DOI: 10.3389/fphar.2022.1063349 -
The American Journal of Cardiology Nov 2023Direct oral anticoagulants (DOACs) are a newer class of anticoagulants that inhibit factor Xa or factor IIa and include drugs such as rivaroxaban, apixaban, edoxaban,... (Meta-Analysis)
Meta-Analysis
An Evidence-Based Approach to Anticoagulation Therapy Comparing Direct Oral Anticoagulants and Vitamin K Antagonists in Patients With Atrial Fibrillation and Bioprosthetic Valves: A Systematic Review, Meta-Analysis, and Network Meta-Analysis.
Direct oral anticoagulants (DOACs) are a newer class of anticoagulants that inhibit factor Xa or factor IIa and include drugs such as rivaroxaban, apixaban, edoxaban, betrixaban, and dabigatran. Although vitamin K antagonists (VKAs) have been traditionally used to prevent thromboembolic events, DOACs have gained popularity because of their faster onset and offset of action and reduced need for monitoring. This study aimed to provide more data for anticoagulants in patients with atrial fibrillation with bioprosthetic heart valves by incorporating all available trials to date. A search was performed across 5 electronic databases to identify relevant studies. We analyzed the data using a pooled risk ratio for categorical outcomes and used the I test to determine heterogeneity. The quality of randomized controlled trials was assessed using the Cochrane risk of bias assessment tool, and the National Institutes of Health tool was used for observational studies. Our study included a frequentist network meta-analysis (MA) of the aggregate data to obtain the network estimates for the outcomes of interest. We retrieved 28 studies with a total of 74,660 patients with bioprosthetic heart valves. Our MA significantly showed that DOACs decrease the risk of all-cause bleeding (risk ratio [RR] 0.80, 95% confidence interval [CI] 0.75 to 0.85, p >0.00001), stroke and systemic embolization (RR 0.89, 95% CI 0.80 to 0.99, p = 0.03), and intracranial bleeding outcomes (RR 0.62, 95% CI 0.45 to 0.86, p = 0.004) compared with VKA. In contrast, there was no significant difference between the compared groups in major bleeding (RR = 0.92, 95% CI 0.84 to 1.02, p = 0.10) and all-cause mortality outcomes (RR = 0.96, 95% CI 0.85 to 1.07, p = 0.43), respectively. In addition, the network MA results did not favor any of the studied interventions over each other (p <0.05) regarding all-cause bleeding, mortality, stroke and systemic embolization, and major bleeding outcomes. In conclusion, our study found that DOACs are more effective in reducing the risk of bleeding, stroke, systemic embolism, and intracranial bleeding than VKAs. However, no significant difference was observed in the incidence of gastrointestinal bleeding, major bleeding, thromboembolic events, and all-cause mortality. In addition, our network MA did not identify any specific DOAC treatment as more favorable than others.
Topics: Humans; Atrial Fibrillation; Network Meta-Analysis; Anticoagulants; Hemorrhage; Stroke; Thromboembolism; Fibrinolytic Agents; Intracranial Hemorrhages; Vitamin K; Administration, Oral
PubMed: 37703679
DOI: 10.1016/j.amjcard.2023.07.141 -
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 -
Journal of Thrombosis and Haemostasis :... Sep 2015Although vitamin K antagonists (VKAs) lower serum values of bone deposition markers, the link with osteoporosis and fractures remains controversial. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Although vitamin K antagonists (VKAs) lower serum values of bone deposition markers, the link with osteoporosis and fractures remains controversial.
OBJECTIVES
To assess whether the use of VKAs is associated with an increased prevalence and/or incidence of osteoporosis, fractures, or lower bone mineral density (BMD) values.
METHODS
We conducted a systematic PubMed and EMBASE literature search until August 31, 2014, and a meta-analysis of cross-sectional and longitudinal studies investigating fractures and BMD, comparing patients treated with VKAs and healthy controls (HCs) or with patients with medical illness (medical controls, MCs). Standardized mean differences ± 95% and confidence intervals (CIs) were calculated for BMD, and risk ratios (RRs) were calculated for prevalent and incident fractures.
RESULTS
Of 4597 initial hits, 21 studies were eligible, including 79 663 individuals treated with VKAs vs. 597,348 controls. Compared with HCs, VKA-treated individuals showed significantly higher fracture risk in cross-sectional (three studies; RR = 1.24; 95% CI: 1.12-1.39, P < 0.0001) and longitudinal studies (seven studies; RR = 1.09; 95% CI: 1.01-1.18, P = 0.03) and more incident hip fractures (four studies; RR = 1.17; 95% CI: 1.05-1.31, P = 0.003). Analyzing studies that matched VKA participants with HCs (four studies), both these findings in longitudinal studies became non-significant. Notably, the VKA and MC group had similar BMD values at all investigated sites. Compared with HCs, a single study showed significantly lower spine T-scores in the VKA-treated group (standardized mean difference = - 0.45; 95% CI: - 0.75, - 0.14, P = 0.004).
CONCLUSION
VKAs neither increased prospectively-assessed fracture risk compared with MCs when matching eliminated confounding factors nor reduced BMD beyond effects of medical illness. Future studies, using careful matching and/or adequate MC groups, are needed to further clarify the short- and long-term effects of VKAs on bone health.
Topics: Adult; Age Factors; Aged; Anticoagulants; Bone Density; Confounding Factors, Epidemiologic; Cross-Sectional Studies; Female; Fractures, Spontaneous; Hip Fractures; Humans; Incidence; Longitudinal Studies; Male; Middle Aged; Observational Studies as Topic; Osteoporosis; Risk; Sex Factors; Vitamin K
PubMed: 26179400
DOI: 10.1111/jth.13052 -
Europace : European Pacing,... Jan 2021Comparative fracture risk for non-vitamin K antagonist oral anticoagulants (NOACs) and vitamin K antagonists (VKAs) among patients with atrial fibrillation (AF) remains... (Meta-Analysis)
Meta-Analysis
AIMS
Comparative fracture risk for non-vitamin K antagonist oral anticoagulants (NOACs) and vitamin K antagonists (VKAs) among patients with atrial fibrillation (AF) remains unclear. This study aimed to provide summary relative risk (RR) estimates for associations between NOACs vs. VKAs and fracture risk.
METHODS AND RESULTS
PubMed, EMBASE, and Cochrane Library were searched from 2010 to 26 May 2020. Observational studies investigating the association between NOACs vs. VKAs and fracture risk in patients with AF were included. The adjusted effect estimates were pooled using the DerSimonian-Laird random effects models. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and the Meta-analysis of Observational Studies in Epidemiological (MOOSE) guidelines were followed. Five observational studies comprising 269 922 patients and 4289 fractures were included. Non-vitamin K antagonist oral anticoagulants use was associated with a lower risk of any fractures compared to VKAs use, with moderate heterogeneity [pooled RR = 0.83, 95% confidence interval (CI): 0.75-0.92, P < 0.001, I2 = 73.0%]. When comparing individual NOAC to VKAs, a statistically significant lower risk of any fractures was found for rivaroxaban (pooled RR = 0.79, 95% CI: 0.71-0.88, P < 0.001, I2 = 55.2%) and apixaban (pooled RR = 0.75, 95% CI: 0.60-0.92, P = 0.007, I2 = 54.5%), but not dabigatran (pooled RR = 0.87, 95% CI: 0.74-1.01, P = 0.061, I2 = 74.6%). No differences were observed in all head-to-head comparisons between NOACs.
CONCLUSION
This large meta-analysis suggests that NOACs use was associated with a lower risk of fractures compared with VKAs. Fracture risks were similar between NOACs. These findings may help inform the optimal anticoagulant choice for patients with AF at high risk of fracture.
Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Dabigatran; Humans; Rivaroxaban; Stroke; Vitamin K
PubMed: 33085751
DOI: 10.1093/europace/euaa242 -
Future Cardiology May 2022To compare real-world effectiveness/safety of non-vitamin K antagonist oral anticoagulants and vitamin K antagonists among patients with non-valvular atrial... (Meta-Analysis)
Meta-Analysis Review
To compare real-world effectiveness/safety of non-vitamin K antagonist oral anticoagulants and vitamin K antagonists among patients with non-valvular atrial fibrillation. A systematic review of electronic databases yielded 7661 citations published from January 2013 to January 2020. Fifty-five studies were included in Bayesian network meta-analyses of hazard ratios. In comparison with vitamin K antagonists, apixaban, dabigatran and rivaroxaban were associated with a reduced risk of stroke or systemic embolism, ischemic stroke, intracranial hemorrhage and all-cause mortality. Apixaban, dabigatran and edoxaban, but not rivaroxaban, were associated with a reduced risk of major bleeding. This study confirmed the effectiveness and safety of non-vitamin K antagonist oral anticoagulants for the treatment of non-valvular atrial fibrillation in real-world settings, consistent with clinical trial evidence.
Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Bayes Theorem; Dabigatran; Fibrinolytic Agents; Humans; Network Meta-Analysis; Pyridones; Rivaroxaban; Stroke; Vitamin K
PubMed: 35360925
DOI: 10.2217/fca-2021-0120 -
Frontiers in Pharmacology 2022We aimed to compare non-vitamin K oral anticoagulants (NOACs) with a traditional antithrombotic such as vitamin K antagonist (VKA) and antiplatelet agents in patients... (Review)
Review
We aimed to compare non-vitamin K oral anticoagulants (NOACs) with a traditional antithrombotic such as vitamin K antagonist (VKA) and antiplatelet agents in patients after transcatheter aortic valve replacement (TAVR). We conducted a search in PubMed, EMBASE, and the Cochrane Library until November 2021 for studies involving comparisons of any type of NOACs, including dabigatran, apixaban, rivaroxaban, and edoxaban, with VKA or antiplatelet agents after TAVR. A comparison of NOACs versus VKA was performed in patients with an indication for oral anticoagulation. In addition, we compared NOACs versus antiplatelet in patients without such indication. We calculated the hazard ratios with 95% confidence intervals (CIs) to determine long-term outcomes. The primary outcome was a combined endpoint consisting of all-cause mortality, stroke, major bleeding, or any related clinical adverse events. Secondary outcomes were all-cause mortality, major bleeding, and stroke, respectively. A total of 10 studies including 10,563 patients after TAVR were included in this meta-analysis. There were no significant differences in any of the long-term outcomes between the NOAC and VKA groups. Although there were no significant differences in the combined endpoint, major bleeding, or stroke, a significant difference was observed in the all-cause mortality (HR 1.74, 95% CI 1.25-2.43, = 0.001) between the NOAC and antiplatelet groups. For patients with an indication for oral anticoagulation after TAVR, NOACs seem to be associated with noninferior outcomes compared with VKA therapy. However, for patients without an indication for oral anticoagulation, NOACs appear to be associated with a higher risk of all-cause death as compared with antiplatelet treatment. https://clinicaltrials.gov/, identifier CRD42020155122.
PubMed: 35222019
DOI: 10.3389/fphar.2022.755009 -
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 -
The American Journal of Medicine Feb 2022Patients with atrial fibrillation and bioprosthetic valves are at high risk for thromboembolic events. The pooled efficacy and safety of non-vitamin K oral... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Patients with atrial fibrillation and bioprosthetic valves are at high risk for thromboembolic events. The pooled efficacy and safety of non-vitamin K oral anticoagulants (NOACs), as a class, relative to warfarin in this population is not well-known. We aimed to compare the efficacy and safety of NOACs relative to warfarin in patients with bioprosthetic valves or valve repair.
METHODS
We systematically searched EMBASE, PubMed, and Cochrane databases for randomized controlled trials comparing NOACs to warfarin in patients with atrial fibrillation and bioprosthetic valves or valve repair. We pooled outcomes for stroke or systemic embolism, ischemic stroke, hemorrhagic stroke, and major bleeding.
RESULTS
We included 4 trials with 1379 patients, of whom 723 (52.4%) received a NOAC. Mean follow-up ranged from 90 days to 2.8 years. In the pooled analysis, stroke or systemic embolism was significantly lower in patients treated with NOACs (1.9%) compared with warfarin (3.7%) (odds ratio [OR] 0.43; 95% confidence interval [CI] 0.22-0.85; P = .02). Ischemic stroke (OR 0.72; 95% CI 0.18-2.93), hemorrhagic stroke (OR 0.18; 95% CI 0.03-1.05), cardiovascular death (OR 0.78; 95% CI 0.38-1.62), and all-cause mortality (OR 0.94; 95% CI 0.55-1.62) were not significantly different among groups. Major bleeding was significantly lower in patients treated with NOAC (2.8%) compared with warfarin (4.7%) (OR 0.49; 95% CI 0.28-0.88; P = .02).
CONCLUSIONS
In patients with atrial fibrillation and bioprosthetic valves or valve repair, NOACs are associated with a reduced incidence of thromboembolic events and major bleeding as compared with warfarin. Thus, NOACs may be considered a preferred option for this patient population.
Topics: Anticoagulants; Atrial Fibrillation; Bioprosthesis; Heart-Assist Devices; Humans; Vitamin K; Warfarin
PubMed: 34634252
DOI: 10.1016/j.amjmed.2021.08.026