Versus Vitamin K Antagonists Research Articles

Comparison of Direct Oral Anticoagulants and Vitamin K Antagonists for Left Ventricular Thrombus: A Global Retrospective Study

IntroductionGuidelines for managing left ventricular thrombus remain limited, particularly when incorporating oral anticoagulants into dual antiplatelet therapy for acute myocardial infarction. This study aims to assess the safety and efficacy of direct oral anticoagulants (DOAC) versus vitamin K antagonist (VKA) in managing left ventricular thrombus among patients with and without recent myocardial infarction. MethodsThis retrospective observational study used data from the TriNetX research network. Patients with left ventricular thrombus treated with either DOACs or VKAs between December 1, 2013, to December 1, 2023, were included. Subgroup analyses were conducted for patients with or without recent acute coronary syndrome (<1 month). Risk and Kaplan-Meier survival analysis were conducted at 90 days since the indexed event. ResultsA total of 39,770 patients were included. DOACs treatment had lower rates of stroke (11.8% vs. 13.7%, RR=0.859, 95% CI 0.816-0.905, p<0.001), major bleeding (4.8% vs. 5.3%, RR=0.902, 95% CI 0.829-0.982, p=0.018), and systemic embolism (3.5% vs. 4.2%, RR=0.841, 95% CI 0.762-0.928, p=0.001) compared to VKAs in overall cohort. Within acute coronary syndrome group (N=14,302), DOACs had lower stroke (12.3% vs. 14.4%, RR=0.860, 95% CI 0.791-0.935, p<0.0001) and systemic embolism (3.1% vs. 4%, RR=0.774, 95% CI 0.651-0.919, p=0.003) risks. For non-acute coronary syndrome group (N=24,162), DOACs had lower stroke (11.4% vs. 13.1%, RR=0.868, 95% CI 0.811-0.929, p<0.001) and major bleeding (4.8% vs. 5.5%, RR=0.877, 95% CI 0.787-0.977, p=0.017) risks. No significant differences in all-cause mortality were observed across groups. ConclusionDOACs demonstrated better safety and efficacy outcomes when compared to VKAs in left ventricular thrombus treatment, with or without recent acute coronary syndrome.

Direct Oral Anticoagulants in Older and Frail Patients with Atrial Fibrillation: A Decade of Experience.

Both the prevalence of atrial fibrillation (AF) and its subsequent use of direct oral anticoagulants (DOACs) are rapidly increasing in patients of older age. In the absence of contra-indications, guidelines advocate anticoagulation based on the CHA2DS2-VASc score for all AF patients aged 75 and above. However, some practitioners are hesitant to prescribe anticoagulants to older and frail patients due to perceived elevated bleeding risks. This review delves into the comparative treatment outcomes of DOACs versus vitamin K antagonists (VKAs) in older patients with AF, particularly focusing on those of advanced age, frailty, increased risk of falling, chronic kidney disease (CKD), or with a history of major bleeding. Additionally, considerations on the use of off-label DOAC doses, the role of left atrial appendage (LAA) closure and future developments in factor XIa-inhibitors will be discussed. While strong evidence supports the use of DOACs in the vital older patients with nonvalvular AF, it remains scant in frail patient groups. There is some evidence from non-randomized studies suggesting that the effect of DOACs compared with VKAs is consistent between frail and nonfrail patients. However, recent findings from a single randomized trial showed increased bleeding risks but comparable thromboembolic outcomes in frail individuals switching from VKAs to DOACs. In patients with an increased risk of falling, data suggest no relevant interaction of increased risk of falling on the effectiveness and safety of DOACs compared with warfarin. Resuming oral anticoagulants in patients with Af after major bleeding seems to be beneficial. Off-label low-dose DOAC is often prescribed to patients who were underrepresented in larger randomized trails because of an elevated risk of bleeding or overexposure to DOACs, but its effect on clinical outcomes remains uncertain. DOACs are the recommended oral anticoagulant for vital older patients with AF. The scarcity of data backing DOAC use in frail individuals, those with renal impairments, or significant bleeding history underscores the necessity for further investigation. However, existing evidence suggests at least similar effectiveness and safety and potential benefits for DOACs in these patient subsets. Therefore, there is no reason to suggest these patients should be treated differently than the established guidelines regarding anticoagulation.

Efficacy of oral anticoagulants in chronic kidney disease and hemodialysis patients with atrial fibrillation: a systematic review and meta-analysis.

This meta-analysis seeks to evaluate the efficacy of direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKA) in individuals with chronic kidney disease (CKD), end-stage renal disease (ESRD), and undergoing hemodialysis (HD) who also have atrial fibrillation (AF). A comprehensive search of MEDLINE, clinicaltrials.gov, EMBASE, and Cochrane Database for relevant studies reporting the usefulness of OAC therapy for CKD, ESRD, and HD patients with AF was conducted from its inception until 1st May 2023. The studies that reported OR, RR, or HR for adult AF patients to investigate the efficacy of OAC in CKD, ESRD, and HD were included. Statistical analysis was completed using a generic inverse variance and random-effects model to calculate the combined HR and their corresponding 95% CIs for all outcomes. The meta-analysis included 33 studies with 178,956 patients. The analysis revealed that the DOACs, when compared to VKA, significantly lowered the risk of stroke or systemic embolism (HR: 0.81 [95% CI: 0.70, 0.93]; P=0.002; I2=62%), bleeding (HR: 0.77, [95% CI: 0.67, 0.89]; P=0.0003; I2=83%), and intracranial hemorrhage (HR: 0.56, [95% CI 0.47, 0.66]; P<0.00001; I2=0%). Similarly, the risks of cardiovascular death (HR: 0.88, [95% CI 0.78, 1.00]; P=0.05; I2=0%), all-cause mortality (HR: 0.88, [95% CI 0.70, 1.10]; P=0.25; I2=96%), and myocardial infarction (HR: 0.80, [95% CI 0.54, 1.17]; P= 0.25; I2= 0%) were lowered by DOAC, but the result was insignificant. No significant difference was seen in the risk of gastrointestinal bleeding between DOAC and VKA as well (HR: 0.95, [95% CI 0.75, 1.20]; P=0.65; I2=83%). Our meta-analysis confirms that DOACs are effective for managing AF in patients with kidney disease, with potential clinical implications for AF and CKD management. Further research should explore DOACs' reno-protective effects.

Apixaban Versus Vitamin K Antagonists in Patients With Antiphospholipid Syndrome: A Cohort Study.

Current guidelines recommend that direct anticoagulants should not be used in prevention of recurrent thrombosis in patients with antiphospholipid syndrome (APS). However, except for triple-positive APS and rivaroxaban use, little evidence supports such recommendation. In a real-life cohort study, we evaluated the risk of thromboembolism and bleeding in patients with APS on apixaban versus vitamin K antagonists (VKA). We enrolled 152 patients with APS (aged 44 years [interquartile range 36-56], 83% women), including 66 patients treated with apixaban 5 mg bid and 86 with warfarin (target international normalized ratio [INR] 2-3). During a median follow-up of 53 months, we recorded venous thromboembolism, ischemic stroke, or myocardial infarction, along with major bleeding. We observed 4 thrombotic events (6.1%, 3 venous thromboembolism and 1 ischemic stroke) in patients on apixaban and 12 events (14%, 9 venous thromboembolism, 2 ischemic strokes and 1 myocardial infarction) in VKA patients. Patients with APS on apixaban had similar risk of recurrent thromboembolism compared with those on warfarin (hazard ratio [HR] = 0.327, 95% confidence interval [CI]: 0.104-1.035). Thromboembolic events occurred less commonly in statin users (8% vs. 50%, P = 0.01) and more frequently in triple-positive APS (50% vs. 22.1%, P = 0.028) and in patients with higher D-dimer at baseline ( P = 0.023); the latter difference was present in the apixaban group ( P = 0.02). Patients on apixaban had similar risk of major bleeding compared with warfarin (HR = 0.54, 95% CI: 0.201-1.448). In real-life patients with APS, apixaban appears to be similar to VKA for the prevention of thromboembolism and risk of bleeding, which might suggest that some patients with APS could be treated with apixaban.

Effectiveness of Direct Oral Anticoagulants and Vitamin K Antagonists in Preventing Stroke in Patients With Atrial Fibrillation and Liver Cirrhosis: A Systematic Review and Meta-Analysis.

Patients with atrial fibrillation and concurrent liver cirrhosis have been excluded from major clinical trials evaluating direct oral anticoagulants (DOACs) due to safety concerns. This has led to uncertainty regarding the optimal anticoagulant therapy in this population at high risk of thromboembolic events. We conducted a systematic review and meta-analysis to compare the effectiveness and safety of DOACs versus vitamin K antagonists (VKAs) in patients with atrial fibrillation and liver cirrhosis. Databases including Embase, MEDLINE/PubMed, and Web of Science were searched for relevant studies. The primary effectiveness outcome was stroke or systemic embolism, and the safety outcome was major bleeding events. A total of 10 studies were included in the meta-analysis. Compared to VKAs, the use of DOACs was associated with a significantly lower risk of stroke or systemic embolism (RR: 0.78, 95% CI: 0.65-0.92, p=0.005). The risk of all-cause mortality was comparable between the two groups (RR: 0.89, 95% CI: 0.74-1.07, p=0.23). Notably, DOACs demonstrated a significantly lower risk of major bleeding events (RR: 0.67, 95% CI: 0.61-0.73, p<0.01) compared to VKAs. This meta-analysis suggests that DOACs may be a favorable alternative to VKAs for the prevention of thromboembolic events in patients with atrial fibrillation and liver cirrhosis, with a lower risk of stroke or systemic embolism and major bleeding. However, further research is needed to establish optimal dosing strategies and assess the safety and efficacy of DOACs in patients with advanced liver disease.

Safety and Outcomes with Direct Oral Anticoagulants Versus Vitamin-K Antagonists in Chronic Thromboembolic Pulmonary Hypertension: A Systematic Review, Meta-Analysis, and Meta-Regression.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a subtype of pulmonary hypertension characterized by organized thrombi inside the pulmonary vasculature, leading to an increase in pulmonary artery pressure. CTEPH is seen in about 3-4% of patients with acute pulmonary embolism and is associated with poor outcomes. Apart from surgical intervention, lifelong anticoagulation is the mainstay of CTEPH management. Traditionally, CTEPH is managed with vitamin-K antagonists (VKA); however, direct oral anticoagulants (DOACs) are recently gaining popularity. However, the current literature comparing DOACs versus VKAs in CTEPH has inconsistent results. An electronic search of the major bibliographic databases was performed to retrieve studies comparing DOACs versus VKAs in CTEPH patients. For dichotomous outcomes, the odds ratio (ORs) with 95% confidence intervals (CI) were pooled using the DerSimonian and Laird random-effects model to generate forest plots. Statistical significance was considered at P < 0.05. Ten studies were included with 3936 patients (1269 in the DOAC group and 2667 in the VKA group). Treatment with DOAC was associated with no statistically significant difference in the risk of all-cause mortality (OR, 0.78; 95% CI, 0.35-1.71; P < 0.53), venous thromboembolism (OR, 1.19; 95% CI, 0.59-2.40; P = 0.63), major bleeding (OR, 0.68; 95% CI, 0.38-1.22; P = 0.20), and clinically relevant nonmajor bleeding (OR, 1.22; 95% CI, 0.80-1.86; P = 0.37). Our analysis demonstrates that DOACs are noninferior to VKAs in terms of their safety and outcomes profile in CTEPH. Further trials are needed to evaluate more robust evidence and to compare additional outcomes.

Direct oral anticoagulants vs Vitamin-K antagonists in solid organ transplant recipients: A systematic review and meta-analysis.

Oure review aimed to examine evidence on the safety and efficacy of direct oral anticoagulants (DOAC) vs Vitamin K antagonists (VKA) in patients with solid organ transplants. PubMed, Embase, and Web of Science libraries were searched from inception to 25th November 2023 for all studies comparing DOAC with VKA in solid organ recipients. Nine studies were included with patients who had undergone kidney, heart, or liver transplants. Meta-analysis showed that patients receiving DOAC had a significantly reduced risk of composite bleeding as compared to those with VKA (RR: 0.45 95% CI: 0.30, 0.68 I2=25%). However, the risk of major bleeding was not significantly different between the two groups (RR: 0.76 95% CI: 0.40, 1.42 I2=37%). Pooled analysis showed that the risk of VTE (RR: 0.90 95% CI: 0.72, 1.13 I2=0%) and ischemic stroke (RR: 0.87 95% CI: 0.39, 1.94 I2=12%) was not significantly different between DOAC and VKA groups. Limited data shows that DOAC are safe and effective in patients with solid organ transplants. The overall risk of bleeding may be reduced with the use of DOAC. There is a need for randomized controlled trials comparing DOAC and VKA in such patients to obtain high-quality evidence.

Comparison of Effectiveness and Safety of Direct-Acting Oral Anticoagulants and Vitamin K Agonists in Patients With Atrial Fibrillation and End-Stage Kidney Disease: A Systematic Review and Meta-Analysis.

The objective of the study is mentioned, but it could be further clarified by explicitly stating the aim to compare the effectiveness and safety of direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs) specifically in patients with atrial fibrillation (AF) and end-stage renal disease (ESRD).We conducted a thorough electronic search of the literature, encompassing databases such as PubMed, EMBASE, Cochrane Library, and Web of Science from their inception up to March 5, 2024. Furthermore, we meticulously examined the bibliographies of included studies to identify additional relevant literature. The reporting of this meta-analysis adhered to the guidelines outlined in the Preferred Reporting of Systematic Review and Meta-analysisguidelines. The endpoints evaluated in this meta-analysis included all-cause mortality, stroke or systemic embolism, and major bleeding. Data analysis was carried out utilizing RevMan Version 5.4 (Cochrane, London, United Kingdom). Dichotomous outcomes, including all-cause mortality, stroke or systemic embolism, and major bleeding, were presented as risk ratios (RRs) with corresponding 95% confidence intervals (CI). A total of 11 studies were incorporated in this meta-analysis, comprising a pooled sample size of 44,863 participants with AF. The pooled analysis revealed no significant disparity between DOACs and VKAs concerning stroke or systemic embolism (RR: 0.93, 95% CI: 0.77 to 1.14) and all-cause mortality (RR: 0.86, 95% CI: 0.74 to 1.00). However, there was a noteworthy reduction in the risk of major bleeding events associated with DOACs compared to VKAs (RR: 0.84, 95% CI: 0.73 to 0.96). Consequently, DOACs may be considered a viable alternative to warfarin in patients with ESRD. However, we need further larger clinical trials to validate these findings.

Gastrointestinal bleeding among oral anticoagulant users: a comprehensive 7-year retrospective review using Türkiye's national health data system.

The comparative risk of gastrointestinal bleeding (GIB) among users of direct-acting oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs) is a topic of ongoing debate. This study leverages a comprehensive national health database to evaluate the incidence of GIB, associated risk factors, and postbleeding management strategies among anticoagulated patients. Utilizing the Turkish Ministry of Health's e-Nabız system, we conducted a retrospective analysis of patients treated with DOACs and warfarin from January 2017 to July 2023. GIB events were identified using ICD codes, and comorbidities, prior medication use, interventions, and mortality rates were analyzed. Drug survival and patterns of changes following GIB were also evaluated. Among 102,545 patients with a GIB event during anticoagulant treatment, DOAC users were older with a higher prevalence of comorbidities, except for chronic obstructive lung disease, compared to VKA users. GIB-related mortality was 0.6% in the DOAC group and 0.4% in the VKA group at admission after the GIB (p < 0.01). In all drug groups, approximately half of the patients discontinued anticoagulation due to GIB after 3 months, the rate being highest with apixaban (61.9%). In patients who continued anticoagulation, the anticoagulant prior to GIB remained the most common agent in all groups, with rivaroxaban having the highest retention rate (40.7%). This nationwide study indicates a higher frequency of GIB in DOAC users versus VKA users, with age and comorbidities potentially contributing to this trend. Mortality rates were comparable to the previous literature but warrant further investigation. The significant rate of discontinuation following GIB raises concerns about ongoing anticoagulation management. These findings underscore the need for cautious case management.

The efficacy and safety of novel oral anticoagulants versus vitamin k antagonist in transcatheter aortic valve replacement patients with indications for anticoagulation

Abstract Introduction Thrombotic events from atrial fibrillation, clinical and subclinical leaflet thromboses continue to be a major concern in Transcatheter Aortic Valve Replacement (TAVR) patients despite technological advancement and operator expertise. The proportion of TAVR patients who have or eventually develop indications for anticoagulation is not negligible and thus may warrant oral anticoagulants. However, the choice of anticoagulation is this select patients remained debatable. Thus, this study was conducted to determine whether current collective data support the efficacy and safety of novel oral anticoagulants (NOACS) versus vitamin K antagonists (VKAs). Purpose Oral anticoagulation (OAC) is necessary but the patients who needed it the most have baseline high bleeding risks. Anticoagulation carries a high bleeding risk especially among majority of a typical post TAVR patients with indications for anticoagulation. The paucity of data among asian TAVR patients were propensity to bleed are prevailing issues with anticoagulation owing perhaps to genetic or race predisposition and lower body weights or BMI compared to non-Asian counterparts. Currently the high court is still out to settle the optimum choice of anti-thrombotic therapy after TAVR. With TAVR now being performed in our local setting, we find this a relevant issue, hence we conducted a meta-analysis. Methods A literature search from Pubmed, Embase, and Cochrane databases for relevant RCTs and observational studies published until February 2022 were conducted. The pooled estimates of all-cause mortality, stroke and major bleeding events were measured using RevMan version 5.4.1 software. Results Eleven eligible studies (9 observational studies and 2 RCTs) allocated 29,156 TAVR patients with indications for anticoagulation either to receive NOACS (n = 11,718) or VKAs (n = 17,468). The effect estimate using random effects model showed no significant differences in all-cause mortality (RR 0.79, 95% CI 0.42–2.25, p = 0.07), stroke (RR 0.96, 95% CI 0.54–2.79, p = 0.70), and major bleeding events (RR 0.82, 95% CI 0.48–1.44, p = 0.08) between the NOACs and VKAs treatment arms. Conclusion NOACs demonstrated non-inferiority over VKA in reducing all-cause mortality, stroke and major or life-threatening bleeding events in TAVR patients with indications for anticoagulation.

Abstract 15692: Clinical Outcomes in TAVR Patients Receiving Oral Anticoagulation Stratified by Baseline Creatinine Clearance Levels: A Subanalysis of the ENVISAGE-TAVI AF Trial

Introduction: The ENVISAGE-TAVI AF (NCT02943785) trial compared edoxaban (EDO) vs vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) after successful transcatheter aortic valve replacement (TAVR). The effect of baseline creatinine clearance (CrCl) on efficacy and safety of EDO vs VKA in these patients is not well understood. Hypothesis: The efficacy and safety of EDO vs VKA in patients with AF undergoing TAVR will vary across the range of baseline CrCl. Methods: In this post-hoc analysis from the ENVISAGE-TAVI AF trial, we stratified patients by oral anticoagulation (OAC) strategy (EDO vs VKA) and CrCl (CrCl ≥90 mL/min, CrCl 60-89 mL/min, CrCl 45-59 mL/min, CrCl 30-44 mL/min, CrCl ≤29 mL/min). Results: Of 1426 patients included, 46.3% (n = 676) had CrCl from 60 to 89 mL/min. Patients with lower CrCl trended older in age than those with higher CrCl ( Table 1 ). The annualized event rates for all outcomes tended to increase with decreasing CrCl ( Table 2 ). Across the range of CrCl, patients receiving EDO vs VKA had higher rates of major bleeding and major gastrointestinal bleeding but lower rates of non-cardiovascular death. Major bleeding did not translate into increased all-cause death. Rates of intracranial hemorrhage were higher with EDO vs VKA in patients with CrCl ≥90 mL/min but lower in all other patients. For all-cause death, differences between EDO and VKA were numerical and did not reach statistical significance. Conclusions: In this ENVISAGE-TAVI AF subanalysis, decrements of CrCl appeared to correlate with rates of adverse outcome parameters more than OAC strategy. Due to low event rates in some outcomes, these results should be interpreted with caution.

Abstract 14237: Anticoagulation Strategies After Transcatheter Aortic Valve Implantation in Patients Without an Indication of Oral Anticoagulants, Network Meta Analysis of Randomized Controlled Trials

Introduction. Transcatheter aortic valve implantation (TAVI) is currently the mainstay treatment for aortic valve diseases, yet postoperative anticoagulation strategies after TAVI is still debatable. Thus, we aim to investigate the safety and efficacy of direct oral anticoagulants (DOACs) vs. single-antiplatelet therapy (SAPTs) vs. dual-antiplatelet therapy (DAPT) vs. Vitamin K antagonists (VKAs) in patients undergoing TAVI and without an indication of OACs. Methods: PubMed, Web of Science, Scopus, and Embase were systematically searched up to December 2022. A frequentist network meta-analysis has been conducted using a random-effects model calculating the odds ratio (OR) with a 95% confidence interval (CI). Results: We included 9,087 patients from 11 studies. Compared to DOACs, DAPT, SAPT, and VKAs were associated with significantly lower odds for short-term all-cause mortality (OR: 0.62; 95% CI [0.46-0.86]), (OR: 0.42; 95% CI [0.29-0.60]), (OR:0.54; 95% CI [0.31, 0.94]), respectively. DAPT was also associated with higher short-term major bleeding risk (OR:2.66; 95% CI [1.46-3.86]). Furthermore, both DAPT and SAPT were associated with significantly higher long-term bleeding rates with (OR: 1.78; 95% CI, [1.15-2.41]) and (OR:2.32; 95% CI, [1.29-3.35]), respectively. However, VKAs were associated with lower long-term bleeding rates (OR: 0.61; 95% CI, [0.24-0.98]). No intervention showed a significant difference over DOACs in terms of long-term all-cause mortality, cardiovascular mortality, and stroke, except for DAPT which showed higher odds of long-term all-cause mortality (OR: 1.83; 95% CI, [1.29-2.37]). Conclusion: Despite the long-term higher rates of major bleeding, SAPT was effective in preventing both short and long-term all-cause mortality compared to DAPT, which has both short, long term major bleeding and higher long-term all-cause mortality. Further RCTs are still required to confirm SAPT superiority compared to other strategies.

Clinical Outcomes in Older Patients with Atrial Fibrillation: Insights from the GARFIELD-AF Registry

BackgroundOral anticoagulants (OAC) are underutilized in older patients with atrial fibrillation, despite proven clinical benefits. Our objective was to investigate baseline characteristics, treatment patterns, and impact of anticoagulation upon clinical outcomes with respect to age. MethodsAdults with newly diagnosed atrial fibrillation were recruited into the prospective observational registry, GARFIELD-AF, and followed up for 24 months. Adjusted hazard ratios (HR) were obtained via Cox proportional-hazards models with applied weights, to quantify the association of age with clinical outcomes. Comparative effectiveness of OAC vs No OAC and non-vitamin K oral anticoagulants (NOAC) vs vitamin K antagonists (VKA) were assessed using a propensity score with an overlap weighting scheme. ResultsOf 52,018 patients, 32.6% were 65-74 years of age, 29.3% were 75-84 years, and 7.9% were ≥85 years. OAC treatment was associated with a numerical reduction in all-cause mortality among those aged 65-74 years (HR; 95% confidence interval) (0.86; 0.69-1.06) and aged 75-84 years (0.89; 0.75-1.05) and a significant reduction in patients ≥85 years (0.77; 0.63-0.95) vs no OAC. Similarly, OACs were associated with a decrease in stroke: 65-74 (0.51; 0.35-0.76) and ≥85 years (0.58; 0.34-0.99) and a numerical decrease in 75-84 years (0.84; 0.59-1.18). No increase in major bleeding was observed in patients aged ≥85 treated with OACs. Compared with VKA, NOACs were associated with a significant reduction in all-cause mortality in patients aged <65 and 65-74, with numerical reductions in those aged 75-84 and ≥85 years. ConclusionsOlder patients using OACs saw lower all-cause mortality and stroke risk; NOACs had less mortality and major bleeding compared with VKAs.

Efficacy and safety of direct oral anticoagulants vs vitamin K antagonists in patients with atrial fibrillation and end-stage renal disease on hemodialysis: A systematic review and meta-analysis

BackgroundThe prevalence of atrial fibrillation (AF) in individuals with end-stage renal disease (ESRD) on chronic hemodialysis is increasing. The optimal anticoagulant choice in this population is unclear since these patients were excluded from the pivotal randomized controlled trials (RCTs) of direct oral anticoagulants (DOACs) vs. vitamin K antagonists (VKAs) in the general AF population. We aimed to assess the efficacy and safety of DOACs vs. VKAs in patients with AF and ESRD on chronic hemodialysis through a systematic review and meta-analysis of all available evidence. Patients/MethodsWe performed a systematic search in MEDLINE and Scopus for RCTs or observational studies of patients with AF and ESRD on chronic hemodialysis who were treated with DOACs or VKAs. The outcomes of interest included ischemic stroke, the composite of ischemic stroke or systemic embolism, major bleeding, gastrointestinal bleeding, minor bleeding events and all-cause mortality. ResultsAmong 397 studies identified from the literature search, six studies (three RCTs and three observational studies) were included in the meta-analysis. Compared with VKA-treated patients, those treated with DOACs had similar risk of ischemic stroke (RR:0.76, 95% CI:0.41–1.41), ischemic stroke or systemic embolism (RR:0.65, 95% CI:0.38–1.10), major bleeding (RR:0.79, 95% CI:0.49–1.28) and all-cause death (RR:0.79, 95% CI:0.56–1.12). The risk of gastrointestinal bleeding was lower in DOAC- vs VKA-treated patients in three eligible observational studies (RR:0.73, 95% CI: 0.54–0.99, I2 = 79%) but this was not confirmed in two eligible RCTs (RR:0.69, 95% CI: 0.33–1.43, I2 = 0%). ConclusionsAmong AF patients with ESRD on chronic hemodialysis, the risk of ischemic stroke, ischemic stroke or systemic embolism, minor bleeding, major bleeding, and all-cause mortality is similar in patients treated with DOACs compared to VKAs. Given that the meta-analysis of RCTs on gastrointestinal bleeding did not confirm the results of the meta-analysis of the observational studies, it cannot be concluded that gastrointestinal bleeding is lower among DOAC-treated patients. Protocol registrationPROSPERO CRD42023391966

The efficacy and safety of direct factor Xa inhibitors versus vitamin K antagonists for atrial fibrillation in patients on hemodialysis: a meta-analysis of randomized controlled trials

Background Direct factor Xa inhibitors have been extensively prescribed for multiple indications; however, hemodialysis patients have been excluded from most of the randomized controlled trials (RCTs) of direct factor Xa inhibitors. Therefore, the efficacy and safety of direct factor Xa inhibitors versus vitamin K antagonists (VKAs) in hemodialysis patients is uncertain. Methods A systematic review and meta-analysis of RCTs was conducted by systematically searching PubMed, EMBASE, Web of Science, SCOPUS, and Cochrane through November 25, 2022. We used the fixed-effect model to pool the risk ratio (RR) with a 95% confidence interval (CI). RevMan v5.4 software was used to pool dichotomous outcomes using RR and continuous outcomes using mean difference presented with the corresponding CI. Results Three RCTs with a total of 341 patients were included in our analysis. There was no difference between direct factor Xa inhibitors and VKAs regarding all-cause mortality (RR, 0.99; 95% CI [0.76, 1.30]; P = 0.96), cardiovascular mortality (RR, 1.35; 95% CI [0.71, 2.60]; P = 0.36), noncardiovascular mortality (RR, 0.75; 95% CI [0.53, 1.05]; P = 0.09), sudden mortality (RR, 1.33; 95% CI [0.53, 3.33]; P = 0.54), any cerebrovascular event (RR, 0.52; 95% CI [0.21, 1.29]; P = 0.16), ischemic stroke (RR, 0.51; 95% CI [0.19, 1.37]; P = 0.18), and hemorrhagic stroke (RR, 0.61; 95% CI [0.10, 3.70]; P = 0.59). Conclusion In patients with atrial fibrillation who are on hemodialysis, direct factor Xa inhibitors and VKAs were similar in terms of efficacy and safety outcomes. However, evidence is still sparse, warranting dedicated RCTs.

Direct oral anticoagulants versus vitamin K antagonist after transcatheter aortic valve implantation

ObjectiveAfter transcatheter aortic valve implantation (TAVI), the optimal regimen of anticoagulant therapy in patients with an additional indication for oral anticoagulation remains a matter of debate. This study investigates the...

Effect of Oral Anticoagulants in Atrial Fibrillation Patients with Polypharmacy: A Meta-analysis.

The aim of the present meta-analysis was to evaluate the effectiveness and safety of non-vitamin K antagonist oral anticoagulants (NOACs) versus vitamin K antagonists (VKAs) in atrial fibrillation (AF) patients with polypharmacy. Randomized controlled trials or observational studies reporting the data of NOACs versus VKAs among AF patients with polypharmacy were included. The search was performed in the PubMed and Embase databases up to November 2022. A total of 12 studies involving 767,544 AF patients were included. For the primary outcomes, the use of NOACs compared with VKAs was significantly associated with a reduced risk of stroke or systemic embolism in AF patients with moderate polypharmacy (hazard ratio [HR]: 0.77 [95% confidence interval [CI]: 0.69-0.86]) and severe polypharmacy (HR: 0.76 [95% CI: 0.69-0.82]), but there was no significant difference in major bleeding (moderate polypharmacy: HR: 0.87 [95% CI: 0.74-1.01]; severe polypharmacy: HR: 0.91 [95% CI: 0.79-1.06]) between the two groups. In secondary outcomes, there were no differences in the rates of ischemic stroke, all-cause death, and gastrointestinal bleeding between the NOAC- and VKA- users, but NOAC users had a reduced risk of any bleeding compared with VKA- users. Compared with VKAs, the risk of intracranial hemorrhage was reduced in NOAC- users with moderate polypharmacy but not severe polypharmacy. In patients with AF and polypharmacy, NOACs showed advantages over VKAs in stroke or systemic embolism and any bleeding, and were comparable to VKAs for major bleeding, ischemic stroke, all-cause death, intracranial hemorrhage, and gastrointestinal bleeding.

Efficacy and safety of non-vitamin K antagonist oral anticoagulants in patients(≥80 Years of Age) with atrial fibrillation: systematic review and meta-analysis.

Findings of prior studies about the efficacy and safety of non-vitamin K antagonist oral anticoagulants in patients(≥80 Years of Age) with atrial fibrillation are controversial. So we perform the meta-analysis to evaluate the efficacy and safety of non-vitamin K antagonist oral anticoagulants versus vitamin-K antagonists (VKAs) in patients(≥80 Years of Age) with atrial fibrillation. A systematic review of PubMed, Cochrane, EmBase, Web of Science, and Chinese BioMedical databases was conducted up to October 1st 2022. Studies reporting the effects and safety of NOACs versus warfarin in patients(≥80 years of age) with atrial fibrillation were included. Two authors independently performed study selection and data extraction. Discrepancies were resolved by consensus or through an independent third reviewer. Data were synthesised according to the Preferred Reporting Items for Systematic Reviews guidelines. We identified 15 studies providing data of 70446 participants(≥80 Years of Age) suffered from atrial fibrillation. On meta-analysis (odds ratio[OR] [95% confidence interval{CI}]), NOACs conferred better efficacy profile than VKAs in stroke and systemic embolism (0.8 [0.73-0.88]) and all-cause mortality(0.61 [0.57-0.65]). Otherwise, NOACs conferred better safety profile than VKAs in major bleeding(0.76 [0.70-0.83]) and intracranial hemorrhage(0.57 [0.47-0.68]). In conclusion, for patients(≥80 Years of Age) with atrial fibrillation, the risks of stroke and systemic embolism, all-cause mortality were lower in NOACs compared to warfarin. While the risks of major bleeding, intracranial hemorrhage were also lower in NOACs compared to warfarin too. NOACs showed better efficacy and safety compared to warfarin. This article is protected by copyright. All rights reserved.

A network meta-analysis of the antithrombotic strategies in patients with atrial fibrillation and percutaneous coronary interventions: Focus on bleeding

BackgroundWe performed a network meta-analysis of randomized controlled trials comparing non-vitamin K antagonist oral anticoagulant (NOAC)-based versus vitamin K antagonists (VKA)-based regimens in patients with atrial fibrillation (AF) and acute coronary syndromes or PCI, aiming to examine the precise impact of recently established antithrombotic strategies on major bleeding as primary end-point and other safety and efficacy as secondary end-points. MethodsA literature search was conducted for randomized controlled trials. Our search took place in three major databases. The primary endpoint of our study was bleeding. To combine direct and indirect evidence across trials, a frequentist network meta-analysis with a random-effects model was used. ResultsFive studies were found eligible for the meta-analysis enrolling a total of 11,542 patients. Five studies (N = 4903 patients) contributed to the network. Compared to the triple antithrombotic therapy (TAT)-based VKA, only the dual antithrombotic therapy (DAT) based NOAC reduced the bleeding (RR 0.57, 95%CI 0.40–0.82). There was no statistically significant difference between DAT-based VKA (RR = 0.66, 95%CI = 0.40–1.09) or TAT-based NOAC (RR = 0.80, 95%CI = 0.43–1.49). DAT-based NOAC ranked best (P-score = 0.91), followed by DAT-based VKA (P-score = 0.67), TAT-based NOAC (P-score = 0.40), and TAT-based VKA (P-score = 0.03). ConclusionThe network meta-analysis of four antithrombotic strategies, demonstrated that in patients with AF undergoing PCI the combination of DAT-based NOAC is associated with a significantly lower risk of major bleeding events. This strategy does not seem to be less effective in terms of prevention of ischemic events compared to the other regimens.

Safety and efficacy of direct oral anticoagulants versus vitamin K antagonists in atrial fibrillation electrical cardioversion: An update systematic review and meta-analysis

BackgroundA systematic evaluation focused on efficacy and safety for electrical cardioversion of atrial fibrillation (AF) among different Direct Oral Anticoagulants (DOACs) has not been previously performed. In this setting, we conducted a meta-analysis of studies evaluating DOACs vs vitamin K antagonists (VKA) as common comparator. MethodsWe searched Cochrane Library, Pubmed, Web Of Science and Scopus databases for all English-only articles concerning studies that have estimated the effect of DOACs and VKA on stroke, transient ischemic attack or systemic embolism (SSE) and major bleeding (MB) events in AF patients undergoing electrical cardioversion. We selected 22 articles comprising 66 cohorts and 24,322 procedures (12,612 with VKA). ResultsDuring follow-up (studies' median 42 days), 135 SSE (52 DOACs and 83 VKA) and 165 MB (60 DOACs and 105 VKA) were recorded. The overall pooled effects, DOACs vs VKA, was estimated by an univariate Odds Ratio of 0.92 (0.63–1.33; p = 0.645) for SSE and 0.58 (0.41–0.82; p = 0.002) for MB; at bivariate evaluation, adjusting for study type, were respectively 0.94 (0.55–1.63; p = 0.834) and 0.63 (0.43–0.92, p = 0.016). Each single DOAC showed similar and non statistically different results in outcome occurrence compared to VKA as well as when Apixaban, Dabigatran, Edoxaban and Rivaroxaban were indirectly compared to each other. ConclusionsIn patients undergoing electrical cardioversion, compared to VKA, DOACs have similar thromboembolic protection with lower major bleeding incidence. Single molecule does not show difference in event rate compared to each other. Our findings, provide useful information about safety and efficacy profile of DOACs and VKA.