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1.
Direct oral anticoagulants versus vitamin K antagonists in epistaxis patients: A systematic review and meta-analysis.
Stanković, P, Hoch, S, Rudhart, S, Obradović, D, Dagres, N, Wilhelm, T
Clinical otolaryngology : official journal of ENT-UK ; official journal of Netherlands Society for Oto-Rhino-Laryngology & Cervico-Facial Surgery. 2022;(2):255-263
Abstract
OBJECTIVE Epistaxis is the most common otolaryngological emergency and up to one third of patients in treated on an inpatient basis take oral anticoagulants (OAC). Direct oral anticoagulants (DOAC), an OAC subgroup, have been on the market since 2010 and are being increasingly prescribed due to the cardiological and haematological guidelines that favour them over vitamin K antagonists (VKA), the older of the OAC subgroups. The present study aims to investigate which subgroup of epistaxis patients taking OACs has a more favourable outcome. DESIGN/SETTING A systematic review and meta-analysis were performed according to the PRISMA 2020 statement using the PubMed and Cochrane Library databases. Continuous data were analysed and standardised mean difference (SMD) was calculated according to Hedges' g. Dichotomous data were analysed, and the Mantel-Haenszel method was applied to establish the odds ratio (OR). Heterogeneity was assessed according to the I2 statistics. MAIN OUTCOME/RESULTS A total of eight reports covering 1390 patients were included in the final synthesis. The pooled analysis demonstrated significantly shorter hospital stays in the DOAC group (SMD = -0.22, 95% CI-0.42 to -0.02, p = .03) and a significantly higher rate of posterior bleeding in the VKA group (OR = .39, 95% CI 0.23 to 0.68, p = .001). No statistically significant differences with regard to recurrence rates, admission rates, the need for transfusion or surgical intervention (p = .57, .12, .57 and .38 respectively) were found. CONCLUSION According to this meta-analysis, epistaxis patients taking DOACs have a more favourable outcome than patients taking VKAs.
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Efficacy and safety of direct oral anticoagulants versus vitamin K antagonist for portal vein thrombosis in cirrhosis: A systematic review and meta-analysis.
Koh, JH, Liew, ZH, Ng, GK, Liu, HT, Tam, YC, De Gottardi, A, Wong, YJ
Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver. 2022;(1):56-62
Abstract
INTRODUCTION AND AIM Portal vein thrombosis (PVT) is associated with a higher risk of liver-related complications. Recent guidelines recommend direct-acting anticoagulants (DOAC) in patients with cirrhosis and non-tumoral PVT. However, data on the efficacy and safety of DOAC in these patients remain limited. We aim to investigate the efficacy and safety of DOAC compared to vitamin K antagonists (VKA) to treat non-tumoral PVT in patients with cirrhosis. METHODS We performed a systematic search of six electronic databases using MeSH term and free text. We selected all studies comparing the use of DOACs with vitamin K antagonist to treat PVT in cirrhosis. The primary outcome was PVT recanalization. Secondary outcomes were and PVT progression, major bleeding, variceal bleeding and death. RESULTS From 944 citations, we included 552 subjects from a total of 11 studies (10 observational and 1 randomized trial) that fulfilled the inclusion criteria. We found that DOAC were associated with a higher pooled rate of PVT recanalization (RR = 1.67, 95%CI: 1.02, 2.74, I2 = 79%) and lower pooled risk of PVT progression (RR = 0.14, 95%CI: 0.03-0.57, I2 = 0%). The pooled risk of major bleeding (RR = 0.29, 95%CI: 0.08-1.01, I2 = 0%), variceal bleeding (RR = 1.29, 95%CI: 0.64-2.59, I2 = 0%) and death (RR = 0.31, 95%CI: 0.01-9.578, I2 = 80%) was similar between DOAC and VKA. CONCLUSION For the treatment of PVT in patients with cirrhosis, the bleeding risk was comparable between DOAC and VKA. However, DOAC were associated with a higher pooled rate of PVT recanalization. Dedicated randomized studies are needed to confirm these findings.
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3.
Non-Vitamin K Antagonists Versus Warfarin in Patients with Atrial Fibrillation and Bioprosthetic Valves: A Systematic Review and Meta-Analysis.
Cardoso, R, Ternes, CMP, Justino, GB, Fernandes, A, Rocha, AV, Knijnik, L, d'Avila, A, Lopes, RD
The American journal of medicine. 2022;(2):228-234.e1
Abstract
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.
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Prevention of nNon-Vitamin K Oral Anticoagulants-Related Gastrointestinal Bleeding With Acid Suppressants: A Systematic Review and Meta-Analysis.
Dong, Y, He, S, Li, X, Zhou, Z
Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis. 2022;:10760296211064897
Abstract
Whether the use of acid suppressants can reduce non-vitamin K oral anticoagulants (NOACs)-related gastrointestinal bleeding (GIB) remains unclear. To systemically evaluate the effect of acid suppressants on the risk of GIB in patients treated with NOACs. All related studies were searched in four databases (Cochrane, Embase, PubMed, and Web of Science) from their establishment to August 10, 2021. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was used to identify studies and Stata 16.0 software was used for meta-analysis, including sensitivity and subgroup analysis. Six retrospective cohort studies were included in this study. The use of acid suppressants significantly reduced the GIB risk in patients taking NOACs, with an overall relative risk (RR) of 0.70 (95% confidence interval [CI]: 0.61-0.82; P < 0.001; I2 = 56.3%). This trend of reduced risk for GIB in NOACs was more significant in upper GIB (UGIB; RR: 0.45; 95%CI: 0.22-0.90; P = 0.025; I2 = 71.1%). The reduction was stronger for dabigatran than for rivaroxaban and apixaban. The least reduction in the risk of GIB with acid suppressant co-therapy was rivaroxaban (dabigatran: RR: 0.53; 95% CI: 0.45-0.62; P = <0.001; I2 = 39.8%; apixaban: RR: 0.67; 95% CI: 0.54-0.84; P = <0.001; I2 = 0; rivaroxaban: RR: 0.73; 95% CI: 0.66-0.81; P = <0.001; I2 = 37.6%). The included studies revealed the protective effect of acid suppressants against NOACs-related GIB, especially in the upper gastrointestinal tract. The protective effect was even stronger in patients using dabigatran than in those using Xa inhibitors (rivaroxaban and apixaban).
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5.
Net clinical benefit of a reduced dose of DOACs in non-valvular atrial fibrillation: A meta-analysis of randomized trials.
Thomopoulos, C, Ntalakouras, J, Polyzos, D, Konstantinidis, D, Palaiodimou, L, Tsivgoulis, G, Tsioufis, C
Pharmacological research. 2022;:105902
Abstract
BACKGROUND In standard dosing, direct Oral Anticoagulants (DOACs) are used as an alternative to warfarin to prevent ischemic stroke and systemic embolism in non-valvular Atrial Fibrillation (AF). However, randomized comprehensive evidence considering the efficacy and safety of the low-dose DOACs in the same setting is still lacking. Toward this end, we conducted a meta-analysis of randomized trials to estimate the risk/benefit ratio, in terms of net clinical benefit, by comparing a reduced dose of DOACs and warfarin. METHODS We searched three electronic databases, covering the period until end-February 2021. All-cause death, non-fatal stroke/systemic embolism, and major bleeding events, with or without the inclusion of myocardial infarction, were used to define two different net clinical benefit outcomes. In addition, we evaluated different component outcomes of net clinical benefit as secondary outcomes. Finally, risk ratios and 95% Confidence Intervals (CI) of each outcome were calculated (random-effects model). RESULTS In the four randomized trials included (n = 29,779 patients), the net clinical benefit - with or without the inclusion of myocardial infarction - of low-dose DOACs, compared to warfarin, was a 12% (95% CI, 7%-16%) or a 10% (95% CI, 5%-13%) reduction of events, respectively. Compared to warfarin, the reduced dose of DOACs decreased death outcomes, major bleeding events, and hemorrhagic stroke, whereas all thrombotic outcomes were not different among the groups. CONCLUSIONS DOACs at low dosing present a more favorable net clinical benefit profile compared to warfarin.
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6.
Comparative Effectiveness and Safety of Non-Vitamin K Antagonist Oral Anticoagulants in Atrial Fibrillation Patients.
Zhu, W, Ye, Z, Chen, S, Wu, D, He, J, Dong, Y, Lip, GYH, Liu, C
Stroke. 2021;(4):1225-1233
Abstract
BACKGROUND AND PURPOSE Several observational studies have compared the effect of the non-vitamin K antagonist oral anticoagulants to each other in patients with atrial fibrillation. However, confounding by indication is a major problem when comparing non-vitamin K antagonist oral anticoagulant treatments in some of these studies. This meta-analysis was conducted to compare the effectiveness and safety between non-vitamin K antagonist oral anticoagulant and non-vitamin K antagonist oral anticoagulant by only including the propensity score matching studies. METHODS We systematically searched the PubMed and Ovid databases until May 2020 to identify relevant observational studies. Hazard ratios (HRs) and 95% CIs of the reported outcomes were collected and then pooled by a random-effects model complemented with an inverse variance heterogeneity or quality effects model. RESULTS A total of 17 retrospective cohort studies were included in this meta-analysis. Compared with dabigatran use, the use of rivaroxaban was significantly associated with increased risks of stroke or systemic embolism (HR, 1.16 [95% CI, 1.05-1.29]) and major bleeding (HR, 1.32 [95% CI, 1.24-1.41]), whereas the use of apixaban was associated with a reduced risk of major bleeding (HR, 0.78 [95% CI, 0.67-0.90]) but not stroke or systemic embolism (HR, 0.84 [95% CI, 0.56-1.28]). Compared with rivaroxaban use, the use of apixaban was associated with a decreased risk of major bleeding (HR, 0.63 [95% CI, 0.54-0.73]) but not stroke or systemic embolism (HR, 0.83 [95% CI, 0.67-1.04]). Reanalyses with the inverse variance heterogeneity or quality effects model produced similar results as the random-effects model. CONCLUSIONS Current observational comparisons with propensity score matching methods suggest that apixaban might be a better choice compared with dabigatran or rivaroxaban for stroke prevention in atrial fibrillation patients.
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Comparison of non-vitamin K antagonist oral anticoagulants on bleeding and thrombosis.
Liu, Z, Ma, L, Zhang, H, Mu, G, Xie, Q, Zhou, S, Wang, Z, Wang, Z, Hu, K, Gong, Y, et al
Journal of clinical pharmacy and therapeutics. 2021;(6):1729-1742
Abstract
WHAT IS KNOWN AND OBJECTIVE Limited data are available for the comparison between different non-vitamin K antagonist oral anticoagulants (NOACs) on clinical outcomes. We aimed to provide evidence of different NOACs for patients with non-valvular atrial fibrillation (NVAF). METHODS Electronic databases were searched from inception through 22 March 2020 to identify eligible studies in which clinical outcomes (stroke, systemic embolism [SE], bleeding or death events) were directly compared between different NOACs. RESULTS 29 real-world studies enrolled more than 700,000 patients were included. Compared with dabigatran, apixaban had higher risk of death (OR 1.07), major bleeding (1.43), GI bleeding (1.64), ischaemic stroke and stroke/SE events (1.10); rivaroxaban had higher risk of death (1.28), major bleeding (1.24), GI bleeding (1.14) and ischaemic stroke (1.08). Compared with rivaroxaban, apixaban had lower risk of death (0.8), major bleeding (0.56) and ischaemic stroke events (0.71). Compared with edoxaban, rivaroxaban had higher risk of major bleeding (2.83), GI bleeding (5.18) and ischaemic stroke (2.28). WHAT IS NEW AND CONCLUSION In view of the global burden of disease and the routine use of NOACs worldwide, the findings have immediate and important implications. Our data suggested that apixaban might be the priority choice in prevention of bleeding and stroke and dabigatran could be the priority choice in prevention of death events. TRIAL REGISTRATION This systematic review and meta-analysis were conducted and reported according to the Preferred Reporting Items for Systematic Reviews (PRISMA), Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines and was registered with PROSPERO (CRD42019140553).
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Prevalence of Left Atrial Thrombus in Anticoagulated Patients With Atrial Fibrillation.
Lurie, A, Wang, J, Hinnegan, KJ, McIntyre, WF, Belley-Côté, EP, Amit, G, Healey, JS, Connolly, SJ, Wong, JA
Journal of the American College of Cardiology. 2021;(23):2875-2886
Abstract
BACKGROUND The prevalence of left atrial (LA) thrombus in patients with atrial fibrillation (AF) or atrial flutter (AFL) on guideline-directed anticoagulation is not well known, yet this may inform transesophageal echocardiogram (TEE) use before cardioversion or catheter ablation. OBJECTIVES The purpose of this study was to quantify LA thrombus prevalence among patients with AF/AFL on guideline-directed anticoagulation and to identify high-risk subgroups. METHODS EMBASE, MEDLINE, and CENTRAL were systematically searched from inception to July 2020 for studies reporting on LA thrombus prevalence among patients with AF/AFL undergoing TEE following at least 3 weeks of continuous therapeutic oral anticoagulation with vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs). Meta-analysis was performed using random effects models. RESULTS Thirty-five studies describing 14,653 patients were identified. The mean-weighted LA thrombus prevalence was 2.73% (95% confidence interval [CI]: 1.95% to 3.80%). LA thrombus prevalence was similar for VKA- and DOAC-treated patients (2.80%; 95% CI: 1.86% to 4.21% vs. 3.12%; 95% CI: 1.92% to 5.03%; p = 0.674). Patients with nonparoxysmal AF/AFL had a 4-fold higher LA thrombus prevalence compared with paroxysmal patients (4.81%; 95% CI: 3.35% to 6.86% vs. 1.03%; 95% CI: 0.52% to 2.03%; p < 0.001). LA thrombus prevalence was higher among patients undergoing cardioversion versus ablation (5.55%; 95% CI: 3.15% to 9.58% vs. 1.65%; 95% CI: 1.07% to 2.53%; p < 0.001). Patients with CHA2DS2-VASc scores ≥3 had a higher LA thrombus prevalence compared with patients with scores ≤2 (6.31%; 95% CI: 3.72% to 10.49% vs. 1.06%; 95% CI: 0.45% to 2.49%; p < 0.001). CONCLUSIONS LA thrombus prevalence is high in subgroups of anticoagulated patients with AF/AFL, who may benefit from routine pre-procedural TEE use before cardioversion or catheter ablation.
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Direct oral anticoagulants in the treatment of acute venous thromboembolism in patients with obesity: A systematic review with meta-analysis.
Mai, V, Marceau-Ferron, E, Bertoletti, L, Lacasse, Y, Bonnet, S, Lega, JC, Provencher, S
Pharmacological research. 2021;:105317
Abstract
BACKGROUND Direct oral anticoagulants' (DOAC) pharmacokinetics are affected by obesity. Their efficacy and safety in obesity (BMI≥30 kg/m2) and morbid obesity (BMI≥40 kg/m2) are still unclear in the treatment of venous thromboembolism (VTE). OBJECTIVES To compare the efficacy/safety of DOAC versus vitamin K antagonist (VKA)/low molecular weight heparin (LMWH) for the treatment of VTE in patients with obesity and morbid obesity. The primary efficacy/safety outcomes were VTE recurrence and major bleeding (MB). Clinically relevant non-MB and mortality were also evaluated. METHODS A systematic literature search (MEDLINE, EMBASE, CENTRAL, Web of Science) identified studies evaluating DOAC in the treatment of VTE in patients with obesity and reporting one of the outcomes. Relative risks (RR) and 95 % confidence intervals (CI) were estimated using the Mantel-Haenszel method. RESULTS We included 21 studies (50,360pts) of which 16,150 patients had a BMI≥30 kg/m2 and 6443 patients had a BMI≥40 kg/m2. VTE recurrence was similar with DOAC compared to VKA/LMWH in patients with obesity (RR 1.03;95 %CI 0.93-1.15;p = 0.55) and morbid obesity (RR 1.06;95 %CI 0.94-1.19;p = 0.35). DOAC were also associated with a reduction in MB (RR 0.57;95 %CI 0.34-0.94;p = 0.03 and RR 0.71;95 %CI 0.50-1.00;p = 0.05 in patients with obesity and morbid obesity, respectively). Subgroup analyses comparing randomized controlled trials to observational studies showed consistent results. No difference was observed in regards of clinically relevant non-MB and mortality. CONCLUSION There is no signal for differences in VTE recurrence in patients with obesity and morbid obesity treated with DOAC compared to VKA/LMWH, while DOAC likely reduce the risk of MB compared to VKA/LMWH.
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Increased bleeding events with the addition of apixaban to the dual anti-platelet regimen for the treatment of patients with acute coronary syndrome: A meta-analysis.
Jin, J, Zhuo, X, Xiao, M, Jiang, Z, Chen, L, Devi Shamloll, Y
Medicine. 2021;(12):e25185
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Abstract
BACKGROUND Dual anti-platelet therapy (DAPT) with aspirin and clopidogrel has been the mainstay of treatment for patients with acute coronary syndrome (ACS). However, the recurrence of thrombotic events, potential aspirin and clopidogrel hypo-responsiveness, and other limitations of DAPT have led to the development of newer oral anti-thrombotic drugs. Apixaban, a new non-vitamin K antagonist, has been approved for use. In this meta-analysis, we aimed to compare the bleeding outcomes observed with the addition of apixaban to DAPT for the treatment of patients with ACS. METHODS Online databases including EMBASE, Cochrane Central, http://www.ClinicalTrials.gov, MEDLINE and Web of Science were searched for English based publications comparing the use of apixaban added to DAPT for the treatment of patients with ACS. Different categories of bleeding events and cardiovascular outcomes were assessed. The analysis was carried out by the RevMan software version 5.4. Odds ratios (OR) with 95% confidence intervals (CI) were used to represent the data following analysis. RESULTS This research analysis consisted of 4 trials with a total number of 9010 participants. Thrombolysis in myocardial infarction (TIMI) defined major bleeding (OR: 2.45, 95% CI: 1.45-4.12; P = .0008), TIMI defined minor bleeding (OR: 3.12, 95% CI: 1.71-5.70; P = .0002), International society of thrombosis and hemostasis (ISTH) major bleeding (OR: 2.49, 95% CI: 1.80-3.45; P = .00001) and Global Use of Strategies to Open Occluded Arteries (GUSTO) defined severe bleeding (OR: 3.00, 95% CI: 1.56-5.78; P = .01) were significantly increased with the addition of apixaban to DAPT versus DAPT alone in these patients with ACS. However fatal bleeding (OR: 10.96, 95% CI: 0.61-198.3; P = .11) was not significantly different. CONCLUSIONS Addition of the novel oral anticoagulant apixaban to the DAPT regimen significantly increased bleeding and therefore did not show any beneficial effect in these patients with ACS. However, due to the extremely limited data, we apparently have to rely on future larger studies to confirm this hypothesis.