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Journal of Thrombosis and Thrombolysis Jan 2022Direct oral anticoagulants (DOACs) are being increasingly used in patients with chronic thromboembolic hypertension (CTEPH), however, the data on their safety and... (Review)
Review
Direct oral anticoagulants (DOACs) are being increasingly used in patients with chronic thromboembolic hypertension (CTEPH), however, the data on their safety and efficacy are scarce and contradictory. We systematically searched MEDLINE and Google Scholar databases from January 2010 to January 2021 for studies of DOACs in CTEPH. Three observational studies, 2 abstracts and one case series met our inclusion criteria. While these studies reported similar or even less rates of major bleeding in patients receiving DOACs compared with vitamin K antagonists, there were concerns about the possibility of increased risk of venous thromboembolism recurrence with DOAC therapy. Further studies are warranted to better define the role of DOACs in CTEPH.
Topics: Administration, Oral; Anticoagulants; Hemorrhage; Humans; Hypertension, Pulmonary; Venous Thromboembolism; Vitamin K
PubMed: 34132973
DOI: 10.1007/s11239-021-02501-8 -
American Journal of Cardiovascular... Mar 2022Patients with atrial fibrillation (AF) have a higher risk of developing thromboembolic events. Current guidelines recommend the use of oral anticoagulants for stroke... (Meta-Analysis)
Meta-Analysis
Comparison of the Efficacy and Safety of Direct Oral Anticoagulants and Vitamin K Antagonists in Patients with Atrial Fibrillation and Concomitant Liver Cirrhosis: A Systematic Review and Meta-Analysis.
BACKGROUND
Patients with atrial fibrillation (AF) have a higher risk of developing thromboembolic events. Current guidelines recommend the use of oral anticoagulants for stroke prevention in these patients. Several clinical trials demonstrated that direct oral anticoagulants (DOACs) have similar efficacy and are safer alternatives to traditional oral anticoagulants. However, patients with concomitant liver cirrhosis were excluded from these trials.
OBJECTIVE
We aimed to systematically identify and review published clinical studies on the use of DOACs in patients with AF and liver cirrhosis and assess the efficacy and safety of DOACs in these patients.
METHODS
A systematic review of clinical trials and retrospective studies was conducted by searching the PubMed, Cochrane Library, Embase, SCOPUS, and Web of Science databases up to September 2020.
RESULTS
Three retrospective studies were included, involving 4011 patients with AF and liver cirrhosis. The use of DOACs was associated with a significant reduction in ischemic stroke (hazard ratio [HR] 0.62; 95% confidence interval [CI] 0.42-0.90; p = 0.01), major bleeding events (HR 0.64; 95% CI 0.57-0.72; p < 0.001), and intracranial hemorrhage (HR 0.49; 95% CI 0.40-0.59; p < 0.001).
CONCLUSIONS
Compared with warfarin in patients with AF and liver cirrhosis, DOACs appear to be associated with improved efficacy and safety outcomes. Randomized controlled trials are warranted to confirm these findings.
Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Liver Cirrhosis; Retrospective Studies; Stroke; Vitamin K
PubMed: 34008145
DOI: 10.1007/s40256-021-00482-w -
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 -
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 -
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 -
Current Problems in Cardiology Mar 2024Pulmonary hypertension (PH) is a known chronic condition that can lead to increased morbidity and mortality. Patients who develop PH due to thromboembolic disease are... (Meta-Analysis)
Meta-Analysis Review
Pulmonary hypertension (PH) is a known chronic condition that can lead to increased morbidity and mortality. Patients who develop PH due to thromboembolic disease are catalogued as chronic thromboembolic pulmonary hypertension (CTEPH). Anticoagulation remains a topic of interest in these patients. PUBMED, EMBASE and COCHRANE databases were searched by two investigators until December 2023. Information was analyzed for all-cause mortality, venous thromboembolism and major bleeding. We included a total of 10 studies in this meta-analysis. Our pooled analysis demonstrated that DOACs were non-inferior in all-cause mortality [OR 0.88, 95 % CI (0.48, 1.61)], venous thromboembolism [OR 1.00, 95 % CI (0.50, 1.98)] and major bleeding [OR 0.78, 95 % CI (0.43, 1.40)] when compared to VKAs. In conclusion, our meta-analysis supports the use of DOACs in patients with CTEPH. Further randomized trials are still needed to confirm our results in terms of safety and mortality.
Topics: Humans; Venous Thromboembolism; Hypertension, Pulmonary; Anticoagulants; Hemorrhage; Fibrinolytic Agents; Vitamin K; Administration, Oral
PubMed: 38184126
DOI: 10.1016/j.cpcardiol.2024.102377 -
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 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 -
American Journal of Cardiovascular... Nov 2023Prevention of ischemic stroke is an essential part of managing atrial fibrillation (AF). In recent years, direct oral anticoagulants (DOACs) have emerged as an... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Prevention of ischemic stroke is an essential part of managing atrial fibrillation (AF). In recent years, direct oral anticoagulants (DOACs) have emerged as an alternative to vitamin K antagonists (VKAs). Little is understood regarding the efficacy and safety of DOACs in AF patients with liver cirrhosis (LC).
OBJECTIVE
This meta-analysis is designed to evaluate the benefits and risks of DOACs compared to VKAs in AF patients with concomitant LC.
METHODS
A thorough search was conducted in PubMed, Cochrane Library, Web of Science, Embase, Scopus, and CNKI databases up to February 2023. A total of seven clinical studies including 7551 patients were analyzed in this meta-analysis. All data analyses were performed using Review Manager software version 5.3.
RESULTS
Regarding efficacy outcomes, DOACs had comparable clinical benefit in reducing ischemic stroke/systemic thromboembolism (HR=0.79, 95% CI [0.59, 1.06], p = 0.12) to VKAs. The incidence of all-cause death was similar between the DOACs and VKAs group (HR 0.94, 95% CI [0.69, 1.28], p = 0.69). Regarding safety outcomes, DOACs were associated with a significantly lower risk of major bleeding (HR 0.61, 95% CI [0.50, 0.75], p < 0.00001), intracranial hemorrhage (HR 0.55, 95% CI [0.31, 0.98], p = 0.04) and major gastrointestinal bleeding (HR 0.66, 95% CI [0.51, 0.85], p = 0.001) than VKAs. Additional subgroup analysis of advanced cirrhosis revealed that DOACs were associated with a significantly lower risk of major bleeding (HR 0.59, 95% CI [0.39, 0.89], p = 0.01) than VKAs. There were no significant differences between the DOACs and VKAs group concerning the incidence of ischemic stroke/systemic thromboembolism (HR 1.38, 95% CI [0.75, 2.55], p = 0.31) and major gastrointestinal bleeding (HR 0.65, 95% CI [0.41, 1.04], p = 0.08).
CONCLUSION
DOACs are associated with more favorable safety outcomes and may be a feasible option of oral anticoagulant for individuals with atrial fibrillation and cirrhosis. Pending validation by randomized prospective studies, the findings of this study should be interpreted with caution.
Topics: Humans; Atrial Fibrillation; Prospective Studies; Anticoagulants; Thromboembolism; Fibrinolytic Agents; Gastrointestinal Hemorrhage; Ischemic Stroke; Liver Cirrhosis; Vitamin K; Administration, Oral; Stroke
PubMed: 37639201
DOI: 10.1007/s40256-023-00598-1 -
European Journal of Nutrition Sep 2019We conducted a meta-analysis to systematically assess the prospective association between vitamin K and cardiovascular disease (CVD) events and all-cause mortality. (Meta-Analysis)
Meta-Analysis
PURPOSE
We conducted a meta-analysis to systematically assess the prospective association between vitamin K and cardiovascular disease (CVD) events and all-cause mortality.
METHODS
We searched PubMed and EMBASE through January 2019 for prospective studies that reported the association of vitamin K (assessed by dietary intake or circulating concentration) with CVD events [including total CVD, CVD mortality, total coronary heart disease (CHD), fatal CHD, nonfatal myocardial infarction (MI), and stroke] and all-cause mortality. Multivariable-adjusted hazard ratios (HRs) comparing top versus bottom tertiles of vitamin K were combined using random-effects meta-analysis.
RESULTS
Twenty-one articles were included with 222,592 participants. A significant association was found between dietary phylloquinone and total CHD (pooled HR 0.92; 95% CI 0.84, 0.99; I = 0%; four studies), as well as menaquinone and total CHD (0.70; 95% CI 0.53, 0.93; I = 32.1%; two studies). No significant association was observed between dietary vitamin K and all-cause mortality, CVD mortality, or stroke. Elevated plasma desphospho-uncarboxylated MGP (dp-ucMGP), a marker of vitamin K deficiency, was associated with an increased risk of all-cause mortality (1.84; 95% CI 1.48, 2.28; I = 16.8%; five studies) and CVD mortality (1.96; 95% CI 1.47, 2.61; I = 0%; two studies). No significant association was observed between circulating total osteocalcin and all-cause mortality or total CVD.
CONCLUSIONS
Our findings showed that higher dietary vitamin K consumption was associated with a moderately lower risk of CHD, and higher plasma dp-ucMGP concentration, but not total circulating osteocalcin, was associated with increased risks of all-cause and CVD mortality. However, causal relations cannot be established because of limited number of available studies, and larger prospective studies and randomized clinical trials are needed to validate the findings.
Topics: Cardiovascular Diseases; Death; Diet; Humans; Risk Factors; Vitamin K
PubMed: 31119401
DOI: 10.1007/s00394-019-01998-3