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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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Real-world oral anticoagulants for Asian patients with non-valvular atrial fibrillation: A PRISMA-compliant article.
Kim, SM, Jeon, ET, Jung, JM, Lee, JS
Medicine. 2021;(32):e26883
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Abstract
BACKGROUND AND PURPOSE This study aimed to evaluate the comparative efficacy and safety of 4 non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin in Asians with non-valvular atrial fibrillation in real-world practice through a network meta-analysis of observational studies. METHODS We searched multiple comprehensive databases (PubMed, Embase, and Cochrane library) for studies published until August 2020. Hazard ratios and 95% confidence intervals were used for the pooled estimates. Efficacy outcomes included ischemic stroke (IS), stroke/systemic embolism (SSE), myocardial infarction (MI), and all-cause mortality, and safety outcomes included major bleeding, gastrointestinal (GI) bleeding, and intracerebral hemorrhage (ICH). The P score was calculated for ranking probabilities. Subgroup analyses were separately performed in accordance with the dosage range of NOACs ("standard-" and "low-dose"). RESULTS A total of 11, 6, and 8 studies were allocated to the total population, standard-dose group, and low-dose group, respectively. In the total study population, edoxaban ranked the best in terms of IS and ICH prevention and apixaban ranked the best for SSE, major bleeding, and GI bleeding. In the standard-dose regimen, apixaban ranked the best in terms of IS and SSE prevention. For major bleeding, GI bleeding, and ICH, edoxaban ranked the best. In the low-dose regimen, edoxaban ranked the best for IS, SSE, GI bleeding, and ICH prevention. For major bleeding prevention, apixaban ranked best. CONCLUSIONS All 4 NOACs had different efficacy and safety outcomes according to their type and dosage. Apixaban and edoxaban might be relatively better and more well-balanced treatment for Asian patients with non-valvular atrial fibrillation.
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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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Fracture Risks in Patients Treated With Different Oral Anticoagulants: A Systematic Review and Meta-Analysis.
Huang, HK, Peng, CC, Lin, SM, Munir, KM, Chang, RH, Wu, BB, Liu, PP, Hsu, JY, Loh, CH, Tu, YK
Journal of the American Heart Association. 2021;(7):e019618
Abstract
Background Evidence on the differences in fracture risk associated with non-vitamin K antagonist oral anticoagulants (NOAC) and warfarin is inconsistent and inconclusive. We conducted a systematic review and meta-analysis to assess the fracture risk associated with NOACs and warfarin. Methods and Results We searched PubMed, Embase, Cochrane Library, Scopus, Web of Science, and ClinicalTrials.gov from inception until May 19, 2020. We included studies presenting measurements (regardless of primary/secondary/tertiary/safety outcomes) for any fracture in both NOAC and warfarin users. Two or more reviewers independently screened relevant articles, extracted data, and performed quality assessments. Data were retrieved to synthesize the pooled relative risk (RR) of fractures associated with NOACs versus warfarin. Random-effects models were used for data synthesis. We included 29 studies (5 cohort studies and 24 randomized controlled trials) with 388 209 patients. Patients treated with NOACs had lower risks of fracture than those treated with warfarin (pooled RR, 0.84; 95% CI, 0.77-0.91; P<0.001) with low heterogeneity (I2=38.9%). NOACs were also associated with significantly lower risks of hip fracture than warfarin (pooled RR, 0.89; 95% CI, 0.81-0.98; P=0.023). A nonsignificant trend of lower vertebral fracture risk in NOAC users was also observed (pooled RR, 0.74; 95% CI, 0.54-1.01; P=0.061). Subgroup analyses for individual NOACs demonstrated that dabigatran, rivaroxaban, and apixaban were significantly associated with lower fracture risks. Furthermore, the data synthesis results from randomized controlled trials and real-world cohort studies were quite consistent, indicating the robustness of our findings. Conclusions Compared with warfarin, NOACs are associated with lower risks of bone fracture.
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Non-Vitamin K Antagonist Oral Anticoagulants Provide Less Adverse Renal Outcomes Than Warfarin In Non-Valvular Atrial Fibrillation: A Systematic Review and MetaAnalysis.
Sitticharoenchai, P, Takkavatakarn, K, Boonyaratavej, S, Praditpornsilpa, K, Eiam-Ong, S, Susantitaphong, P
Journal of the American Heart Association. 2021;(7):e019609
Abstract
Background Non-vitamin K antagonist oral anticoagulants (NOACs) have better pharmacologic properties than warfarin and are recommended in preference to warfarin in most patients with non-valvular atrial fibrillation. Besides lower bleeding complications, other advantages of NOACs over warfarin particularly renal outcomes remain inconclusive. Methods and Results Electronic searches were conducted through Medline, Scopus, Cochrane Library databases, and ClinicalTrial.gov. Randomized controlled trials and observational cohort studies reporting incidence rates and hazard ratio (HR) of renal outcomes (including acute kidney injury, worsening renal function, doubling serum creatinine, and end-stage renal disease) were selected. The random-effects model was used to calculate pooled incidence and HR with 95% CI. Eighteen studies were included. A total of 285 201 patients were enrolled, 118 863 patients with warfarin and 166 338 patients with NOACs. The NOACs group yielded lower incidence rates of all renal outcomes when compared with the warfarin group. Patients treated with NOACs showed significantly lower HR of risk of acute kidney injury (HR, 0.70, 95% CI, 0.64-0.76; P<0.001), worsening renal function (HR, 0.83; 95% CI, 0.73-0.95; P=0.006), doubling serum creatinine (HR, 0.58; 95% CI, 0.41-0.82; P=0.002), and end-stage renal disease (HR, 0.82; 95% CI, 0.78-0.86; P<0.001). Conclusions In non-valvular atrial fibrillation, patients treated with NOACs have a lower risk of both acute kidney injury and end-stage renal disease when compared with warfarin.
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Effect of non-vitamin-K oral anticoagulants on stroke severity compared to warfarin: a meta-analysis of randomized controlled trials.
Costello, M, Murphy, R, Judge, C, Ruttledge, S, Gorey, S, Loughlin, E, Hughes, D, Nolan, A, O'Donnell, MJ, Canavan, M
European journal of neurology. 2020;(3):413-418
Abstract
BACKGROUND AND PURPOSE In addition to lowering stroke risk, warfarin use is also associated with reduced stroke severity in patients with atrial fibrillation and acute ischaemic stroke. It was sought to determine whether the effect of non-vitamin-K oral anticoagulants (NOACs), compared to warfarin, differed by stroke severity. METHODS Phase III randomized controlled trials with participants who were randomized to receive NOACs or warfarin for stroke prevention in the setting of non-valvular atrial fibrillation were identified. Stroke was classified into two categories, fatal or disabling stroke and non-disabling stroke, and meta-analyses were completed for both outcomes and for comparative case fatality of stroke amongst trials. RESULTS Five randomized controlled trials met our inclusion criteria. In clinical trials evaluating the NOACs usually prescribed in clinical practice (four trials), acute stroke was reported in 1403 (1.86%) participants, 787 (1.04%) in the NOAC group [386 (0.51%) fatal or disabling, 401 (0.53%) non-disabling] and 616 (0.82%) in the warfarin group [367 (0.49%) fatal or disabling, 249 (0.33%) non-disabling]. On meta-analysis NOACs were significantly superior to warfarin for fatal or disabling stroke (odds ratio [OR] 0.77; 95% confidence interval [CI] 0.66-0.89, I2 = 21%) and non-disabling stroke (OR 0.85; 95% CI 0.73-0.98, I2 = 2%). The case fatality of stroke was no different between groups (OR 0.90, 95% CI 0.75-1.13, I2 = 0%), but the point estimate favoured NOACs. CONCLUSION In phase III trials of NOACs, for prevention of stroke in atrial fibrillation, NOACs are associated with a lower risk of both fatal/disabling and non-disabling stroke compared to warfarin.
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Real-world comparisons of reduced-dose non-vitamin K antagonist oral anticoagulants versus warfarin in atrial fibrillation: a systematic review and meta-analysis.
Wang, X, Fang, L, Liu, B, Zheng, Y, Zeng, J
Heart failure reviews. 2020;(6):973-983
Abstract
We performed this meta-analysis to compare the efficacy and safety of reduced-dose non-vitamin K antagonist oral anticoagulants (NOACs) versus warfarin in patients with atrial fibrillation (AF). The PubMed and Embase databases were systematically searched until July 2019 for eligible studies that comparing the effect between any reduced-dose NOAC and warfarin in patients with AF. Risk ratios (RRs) and 95% confidence intervals (CIs) were pooled by using a random-effects model. A total of 14 observational cohorts were included. Compared with warfarin use, the use of reduced-dose NOACs was associated with decreased risks of stroke or systemic embolism (RR, 0.83; 95% CI 0.74-0.93), ischemic stroke (RR, 0.87; 95% CI 0.77-0.98), major bleeding (RR, 0.71; 95% CI 0.60-0.84), intracranial hemorrhage (RR, 0.51; 95% CI 0.44-0.60), and gastrointestinal bleeding (RR, 0.72; 95% CI 0.54-0.94), but not all cause death (RR, 0.84; 95% CI 0.67-1.06). In the subgroup analyses, all NOAC users had lower or similar rates of thromboembolic and bleeding events; and the reductions in stroke or systemic embolism, all-cause death, major bleeding, and gastrointestinal bleeding were more prominent in Asians than non-Asians. In conclusion, current published data suggest that the use of reduced-dose NOACs is non-inferior to warfarin in patients with AF (in particular Asians).
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Genetic Factors Influencing Warfarin Dose in Black-African Patients: A Systematic Review and Meta-Analysis.
Asiimwe, IG, Zhang, EJ, Osanlou, R, Krause, A, Dillon, C, Suarez-Kurtz, G, Zhang, H, Perini, JA, Renta, JY, Duconge, J, et al
Clinical pharmacology and therapeutics. 2020;(6):1420-1433
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Abstract
Warfarin is the most commonly used oral anticoagulant in sub-Saharan Africa. Dosing is challenging due to a narrow therapeutic index and high interindividual variability in dose requirements. To evaluate the genetic factors affecting warfarin dosing in black-Africans, we performed a meta-analysis of 48 studies (2,336 patients). Significant predictors for CYP2C9 and stable dose included rs1799853 (CYP2C9*2), rs1057910 (CYP2C9*3), rs28371686 (CYP2C9*5), rs9332131 (CYP2C9*6), and rs28371685 (CYP2C9*11) reducing dose by 6.8, 12.5, 13.4, 8.1, and 5.3 mg/week, respectively. VKORC1 variants rs9923231 (-1639G>A), rs9934438 (1173C>T), rs2359612 (2255C>T), rs8050894 (1542G>C), and rs2884737 (497T>G) decreased dose by 18.1, 21.6, 17.3, 11.7, and 19.6 mg/week, respectively, whereas rs7294 (3730G>A) increased dose by 6.9 mg/week. Finally, rs12777823 (CYP2C gene cluster) was associated with a dose reduction of 12.7 mg/week. Few studies were conducted in Africa, and patient numbers were small, highlighting the need for further work in black-Africans to evaluate genetic factors determining warfarin response.
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The role of non-vitamin K antagonist oral anticoagulants in Asian patients with atrial fibrillation: A PRISMA-compliant article.
Liu, X, Huang, M, Ye, C, Zeng, J, Zeng, C, Ma, J
Medicine. 2020;(27):e21025
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Abstract
BACKGROUND Given the huge burden of atrial fibrillation (AF) and AF-related stroke in Asia, stroke prevention represents an urgent issue in this region. We herein performed a network meta-analysis to examine the role of non-vitamin K antagonist oral anticoagulants (NOACs) in Asian patients with AF. METHODS A systematic search of the publications was conducted in PubMed and Embase databases for eligible studies until July 2019. The odds ratios (ORs) and 95% confidence intervals (CIs) were regarded as the effect estimates. The surface under the cumulative ranking area (SUCRA) for the ranking probabilities was calculated. RESULTS A total of 17 studies were included. For comparisons of NOACs vs warfarin, dabigatran (OR = 0.77, 95% CI 0.68-0.86), rivaroxaban (OR = 0.72, 95% CI 0.65-0.81), apixaban (OR = 0.56, 95% CI 0.49-0.65), but not edoxaban reduced the risk of stroke or systemic embolism, wheres dabigatran (OR = 0.56, 95% CI 0.41-0.76), rivaroxaban (OR = 0.66, 95% CI 0.50-0.86), apixaban (OR = 0.49, 95% CI 0.36-0.66), and edoxaban (OR = 0.34, 95% CI 0.24-0.49) decreased the risk of major bleeding. In reducing the risk of stroke or systemic embolism, apixaban and rivaroxaban ranked the best and second best (SUCRA 0.2% and 31.4%, respectively), followed by dabigatran (50.2%), edoxaban (75.2%), and warfarin (93.0%). In reducing the risk of major bleeding, edoxaban, and apixaban ranked the best and second best (1.5% and 30.8%, respectively), followed by dabigatran (48.4%), rivaroxaban (69.2%), and warfarin (100%). CONCLUSION NOACs were at least as effective as warfarin, but more safer in Asians with AF. Apixaban was superior to other NOACs for reducing stroke or systemic embolism, while edoxaban showed a better safety profile than other NOACs.
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Non-Vitamin K Antagonist Oral Anticoagulants Versus Warfarin in Patients with Atrial Fibrillation with Coronary or Peripheral Artery Disease.
Zhang, H, Xue, Z, Yi, D, Li, X, Tan, Y, Li, J
International heart journal. 2020;(2):231-238
Abstract
The efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOACs) in atrial fibrillation (AF) with coronary or peripheral artery disease (CAD or PAD) remain largely unresolved. We, therefore, conducted a meta-analysis to explore the effect of NOACs compared with warfarin in these populations.We systematically searched the Cochrane Library, PubMed, and Embase databases for randomized controlled trials (RCTs) involving NOACs versus warfarin in AF patients with CAD or PAD. A random-effect model was selected to pool the risk ratios (RRs) and 95% confidence intervals (CIs).A total of 7 RCTs were included. In AF patients with CAD, compared with warfarin use, the use of NOACs was associated with reduced risks of stroke/systemic embolism (RR 0.82; 95% CI 0.70-0.96) and intracranial hemorrhage (RR 0.41; 95% CI 0.26-0.63), but NOACs versus warfarin showed similar risks of all-cause death (RR 0.95; 95% CI 0.86-1.05), cardiovascular death (RR 0.95; 95% CI 0.80-1.13), stroke (RR 0.80; 95% CI 0.64-1.00), myocardial infarction (RR 1.00; 95% CI 0.83-1.21), and major bleeding (RR 0.82; 95% CI 0.65-1.04). Among patients with AF and PAD, NOACs versus warfarin had similar risks for stroke (RR 0.93; 95% CI 0.61-1.42), myocardial infarction (RR 1.10; 95% CI 0.64-1.90), all-cause death (RR 0.91; 95% CI 0.70-1.19), major bleeding (RR 1.12; 95% CI 0.70-1.81), and intracranial hemorrhage (RR 0.54; 95% CI 0.16-1.85).NOACs seem to be at least as effective and safe as warfarin in AF patients with CAD. whereas NOACs versus warfarin have similar efficacy and safety in patients with PAD.