Efficacy Of Anticoagulants Research Articles

The role of anticoagulation in atrial high-rate episodes: a meta-analysis

Abstract Background The role of anticoagulation in patients with atrial high-rate episodes (AHRE), who have no prior history of atrial fibrillation or atrial flutter, is being extensively studied. Purpose Given the increased thrombo-embolic risk in patients who have atrial high-rate episodes, our aim was to evaluate whether anticoagulation leads to enhanced clinical outcomes compared to no anticoagulation (1). Methods We searched PubMed, EMBASE, and the Cochrane Library, through February 2024, for studies evaluating outcomes in patients with atrial high-rate episodes managed with oral anticoagulation (OAC) compared to those not managed with oral anticoagulation. Outcomes assessed were ischemic stroke, thromboembolic events, major bleeding, and all-cause mortality. A fixed-effects model was used to calculate pooled risk risk ratios (RR) and their 95% confidence intervals (CI). Results A total of 4 studies comprising 6788 patients were included. Anticoagulation was associated with a significant reduction in the risks of ischemic stroke (RR 0.66; 95% CI 0.49 - 0.90; P = 0.0084) and thromboembolic events (RR 0.70; 95% CI 0.55 - 0.89; P = 0.0037). Compared to atrial high-rate episodes not managed with anticoagulation, there was a significantly increased risk of major bleeding with anticoagulation (RR 1.57; 95% CI 1.23 - 2.00; P = 0.0002), while the risk of all-cause mortality was similar (RR 1.07; 95% CI 0.95 - 1.21; P = 0.2437). Conclusion Our study suggests that anticoagulation in patients with atrial high-rate episodes decreases the risks of ischemic stroke and thromboembolic events, while increasing the risk of major bleeding, compared patients not managed with anticoagulation. Our study does not show a mortality benefit with the use of anticoagulation in patients with atrial high-rate episodes. Further studies are needed to confirm the safety and efficacy of anticoagulation in atrial high-rate episodes.Forest Plots of Outcomes Assessed

Direct Oral Anticoagulants versus Vitamin K Antagonists for the management of left ventricular thrombus after myocardial infarction: A meta-analysis

Abstract Background/Introduction Left ventricular (LV) thrombus formation is not an uncommon complication after acute myocardial infarction (AMI) in the modern era of early reperfusion. The optimal anticoagulation regimen in this clinical scenario remains poorly-defined. Purpose The present meta-analysis sought to investigate the efficacy and safety profile of direct oral anticoagulants (DOACs) compared with Vitamin K antagonists (VKAs) for the management of LV thrombus following AMI. Methods A systematic literature review was conducted in electronic databases to identify studies reporting efficacy and safety outcome data regarding the use of DOACs versus VKAs for patients with LV thrombus after MI. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated and random-effects meta-analyses were conducted to synthesize pooled ORs. Results Eight studies comprising a total of 605 patients were included (Table). DOACs were associated with an almost 2-fold higher likelihood for achieving thrombus resolution compared to VKAs (pooled OR 1.95 [1.25-3.04]; p =0.003, I2 =0 %), while they achieved a 70% lower risk for systemic embolism (pooled OR 0.30 [0.12-0.75]; p =0.01, I2 =0%). The use of DOACs was associated with a 54% lower risk for bleeding compared to VKAs (pooled OR 0.46 [0.26-0.84]; p =0.01, I2 =0 %). Overall, patients receiving DOACs had a 63% lower risk to reach the composite outcome of any bleeding, systemic embolism, cardiovascular hospitalization, or all-cause death, compared with patients using VKAs (pooled OR 0.37 [0.23-0.60]; p <0.0001, I2 =0%) (Figure). Conclusion DOACs appear to have a more favorable efficacy and safety profile compared to VKAs for the management of LV thrombus following AMI.Graphical abstractTable

Antithrombotic strategies after cryptogenic stroke: a systematic review, pairwise, and network meta-analysis of randomized controlled trials

Abstract Background No definite etiology is identified in 30-40% of ischemic stroke cases, which is known as cryptogenic stroke. Several antithrombotic strategies have been investigated for cryptogenic stroke management; however, the optimal strategy remains unknown. Purpose We aim to assess the efficacy and safety of oral anticoagulants (OACs) versus aspirin, and the comparative efficacy and safety of different OACs after cryptogenic stroke. Methods A systematic review and meta-analysis synthesizing evidence from randomized controlled trials (RCTs) obtained from PubMed, Embase Cochrane, Scopus, and WOS until February 2024. We used the fixed-effects model to report dichotomous outcomes using a risk ratio (RR), with a 95% confidence interval (CI). Analysis was conducted using R, version 4.2.0. Results Seven RCTs with 15.240 patients were included. In pairwise analysis, there was no difference between OACs and aspirin regarding all-cause mortality (RR: 1.13, CI [0.89, 1.43], P= 0.33) and stroke recurrence (RR: 0.93, CI [0.82, 1.07], P= 0.31). However, OACs were associated with a significantly increased incidence of major bleeding (RR: 1.6, CI [1.24, 2.05], P= 0.01), with no difference regarding the incidence of intracranial hemorrhage (RR: 1.09, CI [0.3, 3.97], P= 0.9). Moreover, in network analysis, none of the OACs showed a significant efficacy in preventing all-cause mortality and stroke recurrence compared to aspirin. However, only rivaroxaban significantly increased the incidence of major bleeding (RR: 2.69, CI [1.67, 4.33]). Conclusion OACs did not protect against stroke recurrence or decrease the incidence of all-cause mortality but increased the incidence of major bleeding in patients with cryptogenic stroke.

Oral anticoagulants or antiplatelets for cryptogenic stroke: a systematic review and meta-analysis

Abstract Background Cryptogenic strokes comprise 20 to 30% of ischemic strokes and include a substantial proportion classified as embolic stroke of undetermined source (ESUS). However, the optimal antithrombotic strategy for cryptogenic stroke remains contentious. Purpose We conducted a systematic review and meta-analysis to compare the efficacy and safety of oral anticoagulants (OAC) versus antiplatelets in patients with cryptogenic stroke. Methods Six electronic databases of PubMed, Embase, Web of Science, the Cochrane Library, Google Scholar and ClinicalTrials.gov were searched from inception to Feb 15, 2024 to identify relevant randomized controlled trials (RCTs) comparing stroke recurrence and major bleeding rates between OAC and antiplatelets in cryptogenic stroke patients. We included trials adhering to a stringent diagnostic work-up for cryptogenic stroke, defined as cerebral infarction not attributed to definite sources of cardioembolism, large artery atherosclerosis, or small artery disease despite undergoing comprehensive investigations. The primary outcome was recurrent ischemic stroke, and the secondary outcome was major bleeding based on International Society of Thrombosis and Hemostasis criteria. Subgroup analysis was conducted for ESUS patients with an increased risk of cardiac emboli, such as patent foramen ovale (PFO) and atrial cardiopathy, defined as lead V1 terminal P-wave > 5000 μV × ms in electrocardiogram, serum N-terminal pro-B-type natriuretic peptide level > 250 pg/mL, and left atrial diameter (LAE) > 4 cm, or LAE index ≥ 3 cm/m2 on echocardiogram. Hazard ratio (HR) with 95% confidence (CI) was used as a measure of the effect estimates for aforementioned outcomes. Random-effects meta-analysis was performed using a restricted maximum likelihood model given between-study variance is inevitable. Results Our meta-analysis included 9 RCTs with a total of 15,139 patients (OAC = 7,343; antiplatelets = 7,796). ARCADIA, RE-SPECT ESUS, and NAVIGATE ESUS Trial investigated apixaban, dabigatran, and rivaroxaban, respectively, while warfarin was primarily used as OAC in the remaining six trials. Aspirin was predominantly utilized for antiplatelet therapy. There was no significant difference in recurrent ischemic stroke between OAC and antiplatelets (HR, 0.90; 95% CI, 0.78 to 1.04; I2 = 0%). However, OAC use was associated with a significantly higher risk of major bleeding (HR, 1.66; 95% CI, 1.07 to 2.56; I2 = 36%). Subgroup analysis in ESUS patients revealed comparable rates of recurrent ischemic stroke in those with atrial cardiopathy (HR, 0.91; 95% CI, 0.65 to 1.29; I2 = 0%) and PFO (HR, 0.72; 95% CI, 0.49 to 1.07; I2 = 0%). Conclusions Our meta-analysis suggests that OAC use does not decrease the risk of recurrent ischemic stroke compared with antiplatelet use but is associated with a significantly higher risk of major bleeding in patients with cryptogenic stroke.Primary (A) and secondary (B) outcomesSubgroup analysis for recurrent stroke

Clinical Efficacy and Safety of Novel Anticoagulants for the Management of Venous Thromboembolism in Patients with Cancer: A Systematic Review and Meta-Analysis.

Cancer patients face a four- to sevenfold higher risk of venous thromboembolism (VTE) than the general population. Novel oral anticoagulants (NOACs) provide convenient alternatives to traditional therapies. We performed a systematic literature search across PubMed, Embase, and the Cochrane Library, targeting studies that examined the use of NOACs in cancer-associated VTE. The search included randomized controlled trials (RCTs). Selected studies compared NOACs with low-molecular-weight heparin (LMWH) or vitamin K antagonists (VKA) in cancer patients diagnosed with VTE. A meta-analysis using a random-effects model was applied to estimate pooled effect sizes for outcomes. In this meta-analysis, we included 12 RCTs. Results showed NOACs were more effective than LMWH in preventing VTE recurrence (RR 0.66, 95% CI 0.52-0.83, p = 0.0004). Compared with VKAs, NOACs showed no significant difference (RR 0.63, 95% CI 0.34-1.15, p = 0.13). However, this finding is limited by the small patient sample. Major bleeding outcomes were similar between NOACs and LMWH/VKAs (RR 1.24, 95% CI 0.85-1.80, p = 0.28; RR 0.77, 95% CI 0.39-1.53, p = 0.46, respectively). Meta-regression analysis indicated a statistically significant positive correlation between mortality and major bleeding events when comparing NOACs with LMWH (p = 0.049). There was no significant difference in all-cause mortality between patients treated with NOACs and those treated with LMWH (RR 1.04, 95% CI 0.92-1.18, p = 0.54) or VKAs (RR 0.94, 95% CI 0.72-1.23, p = 0.65). Meta-analysis shows NOACs, especially factor Xa inhibitors, reduce VTE recurrence in cancer patients more effectively than LMWH. Comparison between NOACs and VKAs is inconclusive due to limited patient data. Further research is needed to assess NOACs' efficacy and safety against VKAs.

Efficacy and safety of different oral anticoagulants for stroke prevention in older patients with atrial fibrillation: A network meta-analysis.

Various oral anticoagulants have been used for stroke prevention in older patients with atrial fibrillation (AF). However, the optimal anticoagulants for stroke prevention has not yet been developed. We performed a systematic review and network meta-analysis to determine the optimal instructions. We searched for randomized controlled trials (RCTs) from PubMed, Embase, and the Cochrane Library without restriction for publication date or language at January 2024. Any RCTs that compared the effectiveness of a direct oral anticoagulant and a vitamin K antagonist (VKA) for stroke prevention in older patients with AF were included in this network meta-analysis. The Bayesian network meta-analysis used a random effects model and surface under the cumulative ranking curve analysis to rank results. All analyses were done using R software with gemtc package, with statistical significance set at P < .05. We included 7 RCTs (79,003 patients) comparing 8 different instructions including Apixaban 5 mg, Dabigatran 110 mg, Dabigatran 150 mg, Edoxaban 30 mg, Edoxaban 60 mg, Rivaroxaban 15 mg, Rivaroxaban 20 mg, and VKA. Apixaban 5 mg, Dabigatran 110 mg, and Dabigatran 150 mg was more effective than the VKA for reducing stroke or systemic embolism risks, and the difference was statistically significant (P < .05). Apixaban 5 mg, Dabigatran 110 mg, Dabigatran 150 mg, Edoxaban 30 mg, and Edoxaban 60 mg was associated with a reduction of the intracranial hemorrhage rate than the VKA (P < .05). The surface under the cumulative ranking curve shows that Dabigatran 110 mg ranked first for reducing stroke or systemic embolism risks. Edoxaban 60 mg ranked first for major bleeding. Dabigatran 110 mg ranked first for intracranial hemorrhage. Apixaban 5 mg ranked first for all bleeding events. Direct oral anticoagulants were found to have lower rates of thromboembolic events compared to VKAs in older patients with AF. Apixaban 5 mg, Dabigatran 110 mg, Dabigatran 150 mg, Edoxaban 30 mg, and Edoxaban 60 mg were also associated with a reduction of intracranial hemorrhage than VKA.

Efficacy and Safety of Direct Oral Anticoagulants After Mechanical Thrombectomy in Venous Thromboembolism: A Comparative Study of 55 Patients

Efficacy and Safety of Direct Oral Anticoagulants After Mechanical Thrombectomy in Venous Thromboembolism: A Comparative Study of 55 Patients

Left Ventricular Diastolic Dysfunction with Elevated Filling Pressures Is Associated with Embolic Stroke of Undetermined Source and Atrial Fibrillation.

Background/Objectives: Left ventricular diastolic dysfunction (LVDD) and elevated left ventricular filling pressure (LVFP) are strong predictors of clinical outcomes across various populations. However, their diagnostic utility in embolic stroke of undetermined source (ESUS) remains unclear. We hypothesized that LVDD with elevated LVFP (based on echocardiography) was more likely to be prevalent in ESUS compared to non-cardioembolic stroke (NCE) and to be associated with atrial fibrillation (AF) on follow-up monitoring. Methods: This is a single-center retrospective study that included adult patients with a diagnosis of acute ischemic stroke between January 2016 and June 2017. LV function was assessed by inpatient transthoracic echocardiogram (TTE), and stroke etiology was adjudicated by the neurologist per the consensus criteria. Patients with cardioembolic stroke and those with indeterminate diastolic function on TTE were excluded. Baseline patient characteristics and clinical variables were compared among patients with and without LVDD and elevated LVFP. Multivariable regression models were used to assess the associations between diastolic dysfunction, ESUS, and AF detection in ESUS patients. Results: We identified 509 patients with ESUS and NCE stroke who had reported diastolic function. The mean age was 64.19 years, 45.19% were female, and 146 had LVDD with available LVFP data. LVDD was not associated with ESUS (adjusted OR: 1.43, 95% CI: 0.90-2.27, p = 0.130) or atrial fibrillation (AF) detection on cardiac monitoring (adjusted OR: 1.88, 95% CI: 0.75-4.72, p = 0.179). However, LVDD with elevated LVFP was borderline associated with ESUS (adjusted OR: 2.17, 95% CI: 0.99-4.77, p = 0.054) and significantly associated with AF detection (adjusted OR: 3.59, 95% CI: 1.07-12.06, p = 0.038). Conclusions: Our data suggest that LVDD with elevated LVFP is borderline associated with ESUS and significantly associated with AF detection on follow-up cardiac monitoring. Therefore, the presence of LVDD with an increased probability of elevated LVFP may help identify a subset of stroke patients more likely to have ESUS, potentially due to atrial cardiopathy with underlying occult AF. Further studies are needed to confirm our findings and to evaluate the safety and efficacy of anticoagulation in patients with ESUS and LVDD with elevated LVFP.

Direct Oral Anticoagulants for RheumaticHeart Disease-Associated Atrial Fibrillation Post-Bioprosthetic Mitral Valve Replacement.

The efficacy of direct oral anticoagulants (DOACs) in preventing ischemic and thromboembolic events may be suboptimal in atrial fibrillation (AF) patients with rheumatic mitral stenosis. However, their safety and effectiveness after mitral valve replacement (MVR) using bioprosthetic valves is unclear. This study sought to evaluate the safety and effectiveness of DOACs vs warfarin among patients with rheumatic heart disease (RHD)-associated AF after bioprosthetic MVR. We performed an observational analysis identifying patients with RHD and AF who underwent bioprosthetic MVR. Primary effectiveness and safety outcomes were ischemic events and major bleeding, respectively. Secondary outcomes included all-cause mortality, cardiac thrombosis, myocardial infarction, and all-cause hospitalization. Propensity score matching was performed to account for the differences in baseline characteristics and comorbidities. A total of 3,950 patients were identified; 76% were on warfarin and 24% on DOAC post-MVR. The DOAC group had a higher burden of baseline comorbidities and prior cardiovascular procedures compared with the warfarin group. The propensity score matching balanced baseline characteristics in 1,832 patients (916 in each group), with a mean age of 69 years. At the 5-year follow-up, DOACs were associated with a lower incidence of major bleeding compared with warfarin (HR: 0.76; 95%CI: 0.62-0.94), with no significant difference in ischemic events, mortality, cardiac thrombosis, myocardial infarction, or hospitalization. Among patients with RHD-associated AF patients post-bioprosthetic MVR, DOACs are associated with lower major bleeding and comparable effectiveness, indicating a potential alternative to warfarin. Further randomized controlled trials are warranted to validate these findings in this population.

TCT-5 Safety and Efficacy of Postprocedural Anticoagulation After Primary Percutaneous Coronary Intervention for ST-Segment–Elevation Myocardial Infarction: A Meta-Analysis of RCTs

TCT-5 Safety and Efficacy of Postprocedural Anticoagulation After Primary Percutaneous Coronary Intervention for ST-Segment–Elevation Myocardial Infarction: A Meta-Analysis of RCTs

Direct oral anticoagulant approvals by four major regulatory agencies: a cross-sectional analysis of premarket and postmarket evidence

ObjectivesTo compare the premarket and postmarket evidence of safety and efficacy of direct oral anticoagulants approved for stroke prevention in atrial fibrillation patients across four major regulatory agencies.DesignCross-sectional.SettingEuropean Medicines Association...

Safety and efficacy of direct oral anticoagulants in chronic kidney disease: a meta-analysis

BackgroundDirect oral anticoagulants (DOACs) have emerged as the first-line therapy for venous thromboembolism and stroke prophylaxis in atrial fibrillation. As DOACs are partially excreted renally, their safety in patients with chronic kidney disease (CKD) is unclear. ObjectivesTo synthesize primary evidence on the safety profile of DOACs in patients with CKD. MethodsWe searched MEDLINE and Embase from inception to June 2023 for randomized and nonrandomized cohort studies comparing DOACs with vitamin K antagonists (VKAs) in CKD patients. Screening and data collection were conducted in duplicate. The primary safety outcome was major bleeding, defined by International Society on Thrombosis and Haemostasis criteria, stratified by CKD severity. Meta-analysis was done using the Mantel–Haenszel random-effects model, presented as odds ratios (ORs) with corresponding 95% CIs. ResultsOf the 2355 articles captured in the literature search, 25 nonrandomized studies (n = 6832) and 6 randomized studies (n = 66,898) were included. DOACs reduced major bleeding compared with VKAs in all subgroups (stage 4: OR, 0.73; 95% CI, 0.58, 0.93; stage 5/renal replacement therapy: OR, 0.70; 95% CI, 0.50, 0.98; stage unspecified: OR, 0.72; 95% CI, 0.63, 0.83). Apixaban and rivaroxaban both reduced major bleeding in stage 5/renal replacement therapy patients (apixaban: OR, 0.66; 95% CI, 0.52, 0.85; rivaroxaban: OR, 0.58; 95% CI, 0.35, 0.94). ConclusionIn this meta-analysis, DOACs reduced major bleeding compared with VKAs in stage 4, stage 5/renal replacement therapy, and CKD stage unspecified patients. Future analysis should evaluate the impact of specific DOACs and dosage on safety and efficacy in this population.

Effect of endothelium on the anticoagulant activity of a covalent antithrombin-heparin complex.

We developed a covalent antithrombin-heparin complex (ATH) with superior In vivo anticoagulant efficacy compared to non-covalent antithrombin (AT) + unfractionated heparin (H). Previous in vitro studies of ATH, investigating the mechanisms behind its efficacy, were done in the absence of endothelium. Since the endothelial surface modulates hemostasis, we investigated its impact on the in vitro anticoagulant properties of ATH and AT+H. Discontinuous second order rate constant enzyme inhibition assays, fibrin formation, and plasma clot generation were performed in the presence of ATH or AT+H, with and without endothelium present. ATH had an increased rate of direct inhibition of IIa and Xa, and increased inhibition of IIa-induced fibrin formation, compared to AT+H. When compared at equal anti-Xa levels, ATH was less effective than AT+H at catalyzing inhibition of plasma clot generation. These results were found in both the presence and absence of endothelium. Endothelium decreased the rate of IIa inhibition, and reduced clot time in IIa-induced fibrin formation and plasma clot generation assays, for both ATH and AT+H. Endothelium did not impact the activity of ATH differently to AT+H. This supports the growing body of evidence suggesting ATH may be a beneficial anticoagulant for potential clinical use.

Impact of increasing post-filter ionised calcium target on regional citrate anticoagulation efficacy in ICU continuous renal replacement therapy: the non-inferiority randomised controlled Ca-CIBLE protocol

IntroductionContinuous renal replacement therapy (CRRT) is a critical therapeutic intervention for patients with severe acute kidney injury in intensive care. However, premature filter clotting remains a significant challenge during CRRT,...

Efficacy and Safety of Low or Reduced Dose Direct Oral Anticoagulants Versus Dual Antiplatelet Therapy Following Left Atrial Appendage Closure: A Systematic Review and Meta-Analysis.

This meta-analysis aimed to compare the efficacy and safety of low-dose direct oral anticoagulants (DOACs) versus dual antiplatelet therapy (DAPT) in patients undergoing left atrial appendage closure (LAAC). A comprehensive literature search was conducted across multiple electronic databases, including PubMed, Embase, Cochrane Library, and Scopus, up to August 12, 2024. Studies comparing low-dose DOACs with DAPT in post-LAAC patients were included. The primary outcomes of interest were thromboembolic events, major bleeding, and all-cause mortality. Four studies, including two randomized controlled trials and two observational studies, met the inclusion criteria, with a total of 828 patients (319 in the DOAC group and 509 in the DAPT group). The meta-analysis revealed that patients treated with DOACs had a significantly lower risk of thromboembolic events compared to those receiving DAPT. DOACs were also associated with a significantly reduced risk of device-related thrombosis. Although the risk of stroke was lower in the DOAC group, the difference was not statistically significant. The risk of death did not differ significantly between the two groups. Regarding safety outcomes, patients receiving DOACs experienced fewer bleeding events compared to those on DAPT, with the difference being statistically significant. However, high heterogeneity was reported among the study results for bleeding events. These findings suggest that low-dose DOACs may be a more effective and safer alternative to DAPT for post-LAAC antithrombotic management, particularly in patients at high risk for both thromboembolic and bleeding events. DOACs demonstrated superior efficacy in reducing the risk of stroke, systemic embolism, and other thrombotic complications, while also minimizing bleeding risks.

Anticoagulation for the Prevention of Arterial Thromboembolism in Cancer Patients by Primary Tumor Site: A Systematic Review and Meta-Analysis of Randomized Trials.

Incidence of arterial thromboembolism (ATE) among ambulatory cancer patients varies by primary tumor site. However, it is unclear whether this alters the benefit-to-harm profile of prophylactic anticoagulation for ATE prevention. Therefore, we systematically evaluated the efficacy and safety of anticoagulants for ATE prevention among ambulatory cancer patients according to the primary tumor site. We conducted a systematic review using Medline, Embase, SCOPUS, and CENTRAL, and included randomized trials comparing prophylactic anticoagulation to no anticoagulation among ambulatory cancer patients who initiated tumor-directed systemic therapy. Incidence of symptomatic ATE (acute ischemic stroke, acute myocardial infarction or peripheral artery occlusion) and major bleeding, as well as risk differences (RDs) attributable to anticoagulation were meta-analyzed by primary tumor site using random-effects modeling. We included 10 randomized controlled trials with 9,875 patients with follow-up ranging from 3.3 to 68 (median 6.6) months. While prophylactic anticoagulation did not reduce ATE risks overall (RD -0.49%; 95% CI -0.49% to 0.01%; I2=0%), it conferred a protective effect among pancreatic cancer patients (RD -3.2%; 95%CI -5.7% to -0.8%; I2=0%) without a detectable increase in major bleeding (RD -1.4%; 95% CI -4.6% to 1.8%; I2=0%). Prophylactic anticoagulation was not associated with ATE risk reduction in other tumor sites. Based on available evidence, prophylactic anticoagulation did not reduce ATE risk among ambulatory cancer patients overall. However, we observed lower incidence of ATE among pancreatic cancer patients randomized to receive anticoagulation. Prophylactic anticoagulant use to reduce ATEs in pancreatic cancer should be evaluated in future research.

Venous thrombosis and obesity: from clinical needs to therapeutic challenges.

Weight bias and stigma have limited the awareness of the systemic consequences related to obesity. As the narrative evolves, obesity is emerging as a driver and enhancer of many pathological conditions. Among these, the risk of venous thromboembolism (VTE) is a critical concern linked to obesity, ranking as the third most common cardiovascular condition. Obesity is recognized as a multifactorial risk factor for VTE, influenced by genetic, demographic, behavioral, and socio-economic conditions. Despite established links, the exact incidence of obesity related VTE in the general population remains largely unknown. The complexity of distinguishing between provoked and unprovoked VTE, coupled with gaps in obesity definition and assessment still complicates a tailored risk assessment of VTE risk. Obesity reactivity, hypercoagulability, and endothelial dysfunction are driven by the so-called 'adiposopathy'. This state of chronic inflammation and metabolic disturbance amplifies thrombin generation and alters endothelial function, promoting a pro-thrombotic environment. Additionally, the inflammation-induced clot formation-also referred to as 'immunothrombosis' further exacerbates VTE risk in people living with obesity. Furthermore, current evidence highlights significant gaps in the management of obesity related VTE, particularly concerning prophylaxis and treatment efficacy of anticoagulants in people living with obesity. This review underscores the need for tailored therapeutic approaches and well-designed clinical trials to address the unique challenges posed by obesity in VTE prevention and management. Advanced research and innovative strategies are imperative to improve outcomes and reduce the burden of VTE in people living with obesity.

Direct Oral Anticoagulants versus Vitamin K Antagonists for the Management of Left Ventricular Thrombus after Myocardial Infarction: A Meta-analysis

Left ventricular (LV) thrombus formation remains a post-acute myocardial infarction (AMI) complication even in the modern era of early reperfusion. The optimal anticoagulation regimen in this clinical scenario is poorly defined. The present meta-analysis sought to investigate the efficacy and safety profile of direct oral anticoagulants (DOACs) compared with vitamin K antagonists (VKAs) for the management of LV thrombus after AMI. A systematic literature review was conducted in electronic databases to identify studies reporting efficacy and safety outcome data regarding the use of DOACs versus VKAs for patients with LV thrombus after AMI. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated, and random-effects meta-analyses were conducted to synthesize pooled ORs. Eight studies comprising a total of 605 patients were included. DOACs were associated with an almost twofold higher likelihood of thrombus resolution compared with VKAs (pooled OR 1.95 [1.25 to 3.04], p = 0.003, I2 = 0%), and decreased the risk of systemic embolism by 70% (pooled OR 0.30 [0.12 to 0.75]; p = 0.01, I2 = 0%). The use of DOACs was associated with a 54% lower risk of bleeding compared with VKAs (pooled OR 0.46 [0.26 to 0.84], p = 0.01, I2 = 0%). Overall, patients receiving DOACs had a 63% lower risk of reaching the composite outcome of safety and efficacy compared with patients using VKAs (pooled OR 0.37 [0.23 to 0.60], p <0.0001, I2 = 0%). In conclusion, DOACs appear to have a more favorable efficacy and safety profile compared with VKAs for the management of LV thrombus related to AMI.

Efficacy of novel anticoagulants derived from tick saliva in preventing hypercoagulation among post-acute COVID-19 patients

Efficacy of novel anticoagulants derived from tick saliva in preventing hypercoagulation among post-acute COVID-19 patients

Milvexian vs apixaban for stroke prevention in atrial fibrillation: The LIBREXIA atrial fibrillation trial rationale and design

Direct oral anticoagulants are the standard of care for stroke prevention in eligible patients with atrial fibrillation and atrial flutter; however, bleeding remains a significant concern, limiting their use. Milvexian is an oral Factor XIa inhibitor that may offer similar anticoagulant efficacy with less bleeding risk. LIBREXIA AF (NCT05757869) is a global phase III, randomized, double-blind, parallel-group, event-driven trial to compare milvexian with apixaban in participants with atrial fibrillation or atrial flutter. Participants are randomly assigned to milvexian 100 mg or apixaban (5 mg or 2.5 mg per label indication) twice daily. The primary efficacy objective is to evaluate if milvexian is noninferior to apixaban for the prevention of stroke and systemic embolism. The principal safety objective is to evaluate if milvexian is superior to apixaban in reducing the endpoint of International Society of Thrombosis and Hemostasis (ISTH) major bleeding events and the composite endpoint of ISTH major and clinically relevant nonmajor (CRNM) bleeding events. In total, 15,500 participants from approximately 1,000 sites in over 30 countries are planned to be enrolled. They will be followed until both 430 primary efficacy outcome events and 530 principal safety events are observed, which is estimated to take approximately 4 years. The LIBREXIA AF study will determine the efficacy and safety of the oral Factor XIa inhibitor milvexian compared with apixaban in participants with either atrial fibrillation or atrial flutter. ClinicalTrials.gov NCT05757869.