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1.
Risk of Intracranial Hemorrhage Caused by Direct Oral Anticoagulants for Stroke Prevention in Patients With Atrial Fibrillation (from a Network Meta-Analysis of Randomized Controlled Trials).
Lv, M, Wu, T, Jiang, S, Chen, W, Zhang, J
The American journal of cardiology. 2022;:92-99
Abstract
Patients with atrial fibrillation (AF) who take direct oral anticoagulants (DOACs) face the risk of intracranial hemorrhage (ICH), which can be serious and even life threatening, but the risk of ICH of anticoagulants is still controversial. In this meta-analysis, we compared the risk of ICH between vitamin K antagonists (VKAs) and DOACs. Furthermore, we also compared the risk of ICH in different DOACs. PubMed, Embase, Web of Science, and the Cochrane Library were searched for relevant randomized controlled trials. The outcome was ICH, shown as the odds ratio (OR) with a 95% confidence interval (CI). DOACs were ranked by calculating the surface under the cumulative ranking curve (SUCRA). We included a total of 82,404 patients with AF. DOACs reduced the ICH risk by nearly half compared with VKAs (OR 0.47, 95% CI 0.40 to 0.54, p <0.001). VKAs were the least safe among all oral anticoagulants (SUCRA 1.7). Dabigatran 110 mg was the safest DOAC (SUCRA 87.3) for ICH risk, whereas rivaroxaban 20 mg was a relatively unsafe DOAC (SUCRA 27.5). Compared with rivaroxaban 20 mg, dabigatran 110 mg presented 53% (OR 0.47, 95% CI 0.27 to 0.82) lower relative risk for ICH. In conclusion, DOACs present less ICH risk than VKAs in patients with AF. For patients with AF who are at high risk of ICH, dabigatran 110 mg may be the safest choice among the DOACs.
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2.
Meta-Analysis Comparing the Effect of Rivaroxaban Versus Vitamin K Antagonists for Treatment of Left Ventricular Thrombi.
Saleh, Y, Al-Abcha, A, Abdelkarim, O, Elwany, M, Abdelfattah, OM, Abdelnabi, M, Almaghraby, A
The American journal of cardiology. 2021;:123-125
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3.
Meta-Analysis Investigating the Role of Direct Oral Anticoagulants Versus Vitamin K Antagonists in the Treatment of Left Ventricular Thrombi.
Saleh, Y, Al-Abcha, A, Abdelkarim, O, Abdelnabi, M, Almaghraby, A
The American journal of cardiology. 2021;:126-128
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4.
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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5.
Non-Vitamin K Antagonist Oral Anticoagulants Versus Warfarin for Patients With Left Ventricular Thrombus: A Systematic Review and Meta-Analysis.
Gue, YX, Spinthakis, N, Egred, M, Gorog, DA, Farag, M
The American journal of cardiology. 2021;:147-151
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6.
Efficacy of rivaroxaban in prevention of post-thrombotic syndrome: A systematic review and meta-analysis.
Karathanos, C, Nana, P, Spanos, K, Kouvelos, G, Brotis, A, Matsagas, M, Giannoukas, A
Journal of vascular surgery. Venous and lymphatic disorders. 2021;(6):1568-1576.e1
Abstract
OBJECTIVE Direct oral anticoagulants (DOACs) have been recommended for the treatment of deep vein thrombosis (DVT). However, the benefits are uncertain for the prevention of post-thrombotic syndrome (PTS). We performed a systematic review and meta-analysis of reported studies to assess the efficacy of DOACs vs vitamin K antagonists for the risk reduction of PTS in patients with DVT. METHODS We searched PubMed, Medline, the Cochrane Library, Embase, and the Web of Science for studies reporting on the development of PTS after acute DVT. The outcomes were the risk reduction of PTS, PTS severity, the presence of residual vein thrombosis, and the incidence of recurrent venous thromboembolic (VTE) events. RESULTS A total of 59,199 patients from six retrospective and two randomized controlled studies had received DOAC treatment and were followed up for the development of PTS. In all studies, rivaroxaban had been compared with initial low-molecular-weight heparin followed by warfarin. Of the 59,199 patients, 19,840 (33.5%) had received rivaroxaban and 39,377 (66.5%), warfarin. The rivaroxaban group had a significant reduction in PTS development compared with the warfarin group (odds ratio [OR], 0.52; 95% confidence interval [CI], 0.43-0.63; P < .001). Severe PTS was less common in the rivaroxaban group than in the warfarin group (3.7% vs 6.4%; OR, 0.55; 95% CI, 0.36-0.85; P = .024). Additionally, rivaroxaban was associated with a significant reduction in VTE recurrence (OR, 0.83; 95% CI, 0.59-1.18; P = .03) and low rates of residual vein thrombosis compared with warfarin (36.5% vs 51.8%; P = .037). CONCLUSIONS Rivaroxaban after acute DVT was associated with a reduced risk of PTS compared with warfarin. Patients treated with rivaroxaban more rarely developed severe PTS and recurrent VTE events compared with patients treated with warfarin.
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7.
Efficacy and safety of reduced-dose non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation: a meta-analysis of randomized controlled trials.
Wang, KL, Lopes, RD, Patel, MR, Büller, HR, Tan, DS, Chiang, CE, Giugliano, RP
European heart journal. 2019;(19):1492-1500
Abstract
AIMS: Non-vitamin K antagonist oral anticoagulants (NOACs) require dose reductions according to patient or clinical factors for patients with atrial fibrillation (AF). In this meta-analysis, we aimed to assess outcomes with reduced-dose NOACs when given as pre-specified in pivotal trials. METHODS AND RESULTS Aggregated data abstracted from Phase III trials comparing NOACs with warfarin in patients with AF were assessed by treatment using risk ratios (RRs) and 95% confidence intervals (CIs) stratified by patient eligibility for NOAC dose reduction. Irrespective of treatments, annualized rates of stroke or systemic embolism and major bleeding were higher in patients eligible for reduced-dose NOACs than in those eligible for full-dose NOACs (2.70% vs. 1.60% and 4.35% vs. 2.87%, respectively). Effects of reduced-dose NOACs compared with warfarin in patients eligible for reduced-dose NOACs on stroke or systemic embolism [RR 0.84 (95% CI 0.69-1.03)] and on major bleeding [RR 0.70 (95% CI 0.50-0.97)] were consistent with those of full-dose NOACs relative to warfarin in those eligible for full-dose NOACs [RR 0.86 (95% CI 0.77-0.96) for stroke or systemic embolism and RR 0.87 (95% CI 0.70-1.08) for major bleeding; interaction P, 0.89 and 0.26, respectively]. In addition, NOACs were associated with reduced risks of haemorrhagic stroke, intracranial haemorrhage, fatal bleeding, and death regardless of patient eligibility for NOAC dose reduction (interaction P > 0.05 for each). CONCLUSIONS Patients eligible for reduced-dose NOACs were at elevated risk of thromboembolic and haemorrhagic complications when treated with anticoagulants. NOACs, when appropriately dose-adjusted, had an improved benefit-harm profile compared with warfarin. Our findings highlight the importance of prescribing reduced-dose NOACs for indicated patient populations.
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8.
Extended Anticoagulation for VTE: A Systematic Review and Meta-Analysis.
Mai, V, Guay, CA, Perreault, L, Bonnet, S, Bertoletti, L, Lacasse, Y, Jardel, S, Lega, JC, Provencher, S
Chest. 2019;(6):1199-1216
Abstract
BACKGROUND The efficacy and safety of direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) during extended anticoagulation for a VTE remains largely unknown, especially in terms of potential survival benefit. The goal of this study was to assess the effects of VKAs and DOACs on overall mortality and VTE-related mortality, as well as VTE recurrence and safety. METHODS PubMed, EMBASE, and the Cochrane Library were searched from January 1990 through September 2018 for randomized controlled trials evaluating the effect of extended anticoagulants as secondary prevention for VTE compared with placebo. The primary outcome was the specific effects of standard-intensity VKAs and DOACs on overall mortality. RESULTS Sixteen studies (12,458 patients) were included. DOACs were associated with a reduction in overall (risk ratio [RR], 0.48; 95% CI, 0.27-0.86; P = .01) and VTE-related (RR, 0.36; 95% CI, 0.15-0.89; P = .03) mortality, whereas VKAs were not (P > .50). Although VKAs and DOACs similarly prevented recurrent VTE, only VKAs were associated with an increased risk of major bleeding (RR, 2.67; 95% CI, 1.28-5.60; P < .01), resulting in an improved net clinical benefit for DOACs (RR, 0.25 [95% CI, 0.16-0.39; P < .01] vs 0.46 [95% CI, 0.30-0.72; P < .01]; Pinteraction = .05). CONCLUSIONS DOACs for extended anticoagulation were associated with a significant reduction in overall mortality compared with observation alone. TRIAL REGISTRY PROSPERO; No.: CRD42018088739; URL: https://www.crd.york.ac.uk/prospero/.
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9.
Non-Vitamin K Antagonist Oral Anticoagulants Versus Warfarin in Patients With Cancer and Atrial Fibrillation: A Systematic Review and Meta-Analysis.
Deng, Y, Tong, Y, Deng, Y, Zou, L, Li, S, Chen, H
Journal of the American Heart Association. 2019;(14):e012540
Abstract
Background Several studies have investigated the effect of non-vitamin K antagonist oral anticoagulants (NOACs) in atrial fibrillation (AF) patients with cancer, but the results remain controversial. Therefore, we conducted a meta-analysis to compare the efficacy and safety of NOACs versus warfarin in this population. Methods and Results We systematically searched the PubMed and Embase databases until February 16, 2019 for studies comparing the effect of NOACs with warfarin in AF patients with cancer. Risk ratios (RRs) with 95% CIs were extracted and pooled by a random-effects model. Five studies involving 8908 NOACs and 12 440 warfarin users were included. There were no significant associations between cancer status and risks of stroke or systemic embolism, major bleeding, or death in AF patients. Compared with warfarin, NOACs were associated with decreased risks of stroke or systemic embolism (RR, 0.52; 95% CI, 0.28-0.99), venous thromboembolism (RR, 0.37, 95% CI, 0.22-0.63), and intracranial or gastrointestinal bleeding (RR, 0.65; 95% CI, 0.42-0.98) and with borderline significant reductions in ischemic stroke (RR, 0.63; 95% CI, 0.40-1.00) and major bleeding (RR, 0.73; 95% CI, 0.53-1.00). In addition, risks of efficacy and safety outcomes of NOACs versus warfarin were similar between AF patients with and without cancer. Conclusions In patients with AF and cancer, compared with warfarin, NOACs had lower or similar rates of thromboembolic and bleeding events and posed a reduced risk of venous thromboembolism.
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10.
Factor Xa inhibitors versus vitamin K antagonists for preventing cerebral or systemic embolism in patients with atrial fibrillation.
Bruins Slot, KM, Berge, E
The Cochrane database of systematic reviews. 2018;(3):CD008980
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Abstract
BACKGROUND Factor Xa inhibitors and vitamin K antagonists (VKAs) are now recommended in treatment guidelines for preventing stroke and systemic embolic events in people with atrial fibrillation (AF). This is an update of a Cochrane review previously published in 2013. OBJECTIVES To assess the effectiveness and safety of treatment with factor Xa inhibitors versus VKAs for preventing cerebral or systemic embolic events in people with AF. SEARCH METHODS We searched the trials registers of the Cochrane Stroke Group and the Cochrane Heart Group (September 2016), the Cochrane Central Register of Controlled Trials (CENTRAL) (August 2017), MEDLINE (1950 to April 2017), and Embase (1980 to April 2017). We also contacted pharmaceutical companies, authors and sponsors of relevant published trials. We used outcome data from marketing authorisation applications of apixaban, edoxaban and rivaroxaban that were submitted to regulatory authorities in Europe and the USA. SELECTION CRITERIA We included randomised controlled trials (RCTs) that directly compared the effects of long-term treatment (lasting more than four weeks) with factor Xa inhibitors versus VKAs for preventing cerebral and systemic embolism in people with AF. DATA COLLECTION AND ANALYSIS The primary efficacy outcome was the composite endpoint of all strokes and systemic embolic events. Two review authors independently extracted data, and assessed the quality of the trials and the risk of bias. We calculated a weighted estimate of the typical treatment effect across trials using the odds ratio (OR) with 95% confidence interval (CI) by means of a fixed-effect model. In case of moderate or high heterogeneity of treatment effects, we used a random-effects model to compare the overall treatment effects. We also performed a pre-specified sensitivity analysis excluding any open-label studies. MAIN RESULTS We included data from 67,688 participants randomised into 13 RCTs. The included trials directly compared dose-adjusted warfarin with either apixaban, betrixaban, darexaban, edoxaban, idraparinux, idrabiotaparinux, or rivaroxaban. The majority of the included data (approximately 90%) was from apixaban, edoxaban, and rivaroxaban.The composite primary efficacy endpoint of all strokes (both ischaemic and haemorrhagic) and non-central nervous systemic embolic events was reported in all of the included studies. Treatment with a factor Xa inhibitor significantly decreased the number of strokes and systemic embolic events compared with dose-adjusted warfarin in participants with AF (OR 0.89, 95% CI 0.82 to 0.97; 13 studies; 67,477 participants; high-quality evidence).Treatment with a factor Xa inhibitor significantly reduced the number of major bleedings compared with warfarin (OR 0.78, 95% CI 0.73 to 0.84; 13 studies; 67,396 participants; moderate-quality evidence). There was, however, statistically significant and high heterogeneity (I2 = 83%). When we repeated this analysis using a random-effects model, it did not show a statistically significant decrease in the number of major bleedings (OR 0.88, 95% CI 0.66 to 1.17). A pre-specified sensitivity analysis excluding all open-label studies showed that treatment with a factor Xa inhibitor significantly reduced the number of major bleedings compared with warfarin (OR 0.75, 95% CI 0.69 to 0.81), but high heterogeneity was also observed in this analysis (I2 = 72%). The same sensitivity analysis using a random-effects model also showed a statistically significant decrease in the number of major bleedings in participants treated with factor Xa inhibitors (OR 0.76, 95% CI 0.60 to 0.96).Treatment with a factor Xa inhibitor significantly reduced the risk of intracranial haemorrhages (ICHs) compared with warfarin (OR 0.50, 95% CI 0.42 to 0.59; 12 studies; 66,259 participants; high-quality evidence). We observed moderate, but statistically significant heterogeneity (I2 = 55%). The pre-specified sensitivity analysis excluding open-label studies showed that treatment with a factor Xa inhibitor significantly reduced the number of ICHs compared with warfarin (OR 0.47, 95% CI 0.40 to 0.56), with low, non-statistically significant heterogeneity (I2 = 27%).Treatment with a factor Xa inhibitor also significantly reduced the number of all-cause deaths compared with warfarin (OR 0.89, 95% 0.83 to 0.95; 10 studies; 65,624 participants; moderate-quality evidence). AUTHORS' CONCLUSIONS Treatment with factor Xa inhibitors significantly reduced the number of strokes and systemic embolic events compared with warfarin in people with AF. The absolute effect of factor Xa inhibitors compared with warfarin treatment was, however, rather small. Factor Xa inhibitors also reduced the number of ICHs, all-cause deaths and major bleedings compared with warfarin, although the evidence for a reduction in the latter is less robust.