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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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Comparison of Anticoagulation Quality between Acenocoumarol and Warfarin in Patients with Mechanical Prosthetic Heart Valves: Insights from the Nationwide PLECTRUM Study.
Menichelli, D, Poli, D, Antonucci, E, Cammisotto, V, Testa, S, Pignatelli, P, Palareti, G, Pastori, D, The Italian Federation Of Anticoagulation Clinics Fcsa,
Molecules (Basel, Switzerland). 2021;(5)
Abstract
Vitamin K antagonists are indicated for the thromboprophylaxis in patients with mechanical prosthetic heart valves (MPHV). However, it is unclear whether some differences between acenocoumarol and warfarin in terms of anticoagulation quality do exist. We included 2111 MPHV patients included in the nationwide PLECTRUM registry. We evaluated anticoagulation quality by the time in therapeutic range (TiTR). Factors associated with acenocoumarol use and with low TiTR were investigated by multivariable logistic regression analysis. Mean age was 56.8 ± 12.3 years; 44.6% of patients were women and 395 patients were on acenocoumarol. A multivariable logistic regression analysis showed that patients on acenocoumarol had more comorbidities (i.e., ≥3, odds ratio (OR) 1.443, 95% confidence interval (CI) 1.081-1.927, p = 0.013). The mean TiTR was lower in the acenocoumarol than in the warfarin group (56.1 ± 19.2% vs. 61.6 ± 19.4%, p < 0.001). A higher prevalence of TiTR (<60%, <65%, or <70%) was found in acenocoumarol users than in warfarin ones (p < 0.001 for all comparisons). Acenocoumarol use was associated with low TiTR regardless of the cutoff used at multivariable analysis. A lower TiTR on acenocoumarol was found in all subgroups of patients analyzed according to sex, hypertension, diabetes, age, valve site, atrial fibrillation, and INR range. In conclusion, anticoagulation quality was consistently lower in MPHV patients on acenocoumarol compared to those on warfarin.
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ABCA1 Polymorphism Is Associated With the Warfarin-Induced Aortic Stiffness After Coronary Artery Bypass Surgery in the Chinese Population.
Liao, S, Zhou, Q, Zhang, Y
Journal of cardiovascular pharmacology. 2020;(3):360-366
Abstract
Warfarin is the most widely prescribed oral anticoagulant and is recommended for patients recovering from coronary artery bypass graft (CABG) with atrial fibrillation. Increasing evidence suggested that warfarin increased arterial stiffness in those patients. We aimed to examine the effect of warfarin therapy on aortic stiffness in patients who underwent CABG with or without postoperative warfarin treatment and explored the potential relationships of warfarin therapy with ABCA1 polymorphisms. This was a retrospect observational study of 24 patients who were continuously treated with warfarin were selected as the warfarin group and matched them by age (±3 years) and gender to 48 patients with nonuse of warfarin as the control group. The aortic stiffness, cholesterol efflux capacity, and plasma level of PIVKA-II were measured. Two ABCA1 polymorphisms were genotyped. Compared with baseline, treatment with warfarin for 1 year significantly increased the plasma level of PIVKA-II and aortic stiffness in pulse pressure and pulse wave velocity in patients after CABG. The increase of pulse wave velocity and plasma PIVKA-II level in the TT genotype was significantly greater than the CC genotype when comparing the -565C/T genotypes. The capacity of cholesterol efflux was significantly lower in the TT genotype at baseline and 1-year follow-up than the CC genotype. Postoperative treatment of warfarin for 1 year significantly increased aortic stiffness in patients who underwent CABG. ABCA1 -565C/T polymorphisms affected the cholesterol efflux capacity and were associated with the vitamin K status and the increased aortic stiffness after warfarin treatment in those patients.
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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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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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Quantitative Volumetric Comparison of Direct Oral Anticoagulant and Vitamin K Antagonist Treatment for Pulmonary Thrombus Reduction During the Acute Phase in Symptomatic Patients.
Jujo, K, Yoshida, A, Fukushima, K, Kikuchi, Y, Minami, Y, Murasaki, K, Haruki, S, Sekiguchi, H, Tanaka, H, Ogawa, H, et al
The American journal of the medical sciences. 2020;(2):153-160
Abstract
BACKGROUND Recent clinical trials' findings have revealed the therapeutic noninferiority of direct oral anticoagulant (DOAC) to standard therapy with vitamin K antagonist (VKA) in patients with pulmonary thromboembolism (PTE). However, few studies have quantitatively analyzed thrombus reduction in the pulmonary artery. METHODS This observational study included 38 symptomatic PTE patients with stable hemodynamics. All patients received an intravenous heparin bolus followed by continual heparin injections immediately after the PTE diagnosis. The heparin was discontinued after edoxaban therapy began in the DOAC group (n = 22) or after the therapeutic range for the prothrombin time-international normalized ratio was achieved in the VKA group (n = 16). The thrombus volumes in the pulmonary arteries were quantitatively analyzed using contrast-enhanced computed tomography scans, and they were compared at baseline and at 2 weeks after admission. RESULTS The pulmonary thrombus volumes declined in the VKA and DOAC groups from 7.9 to 4.2 cm3 (P = 0.048) and from 7.1 to 3.7 cm3 (P < 0.01), respectively, and the thrombus reduction rates did not differ significantly between the groups (-34% vs. -64%, respectively; P = 0.38). The fibrinogenolysis parameter changes during the14 days after admission were similar in both groups. Compared with the VKAgroup, the average hospital stay was 9days shorter in the DOAC group. There were no in-hospital deaths, and 1 case experienced major bleeding in the VKA group. CONCLUSIONS In relation to pulmonary artery thrombus volume reduction, DOAC monotherapy for PTE may be comparable with standard therapy involving VKAs.
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Meta-analysis of the efficacy and safety of non-vitamin K antagonist oral anticoagulants with warfarin in Latin American patients with atrial fibrillation.
Su, Z, Zhang, H, He, W, Ma, J, Zeng, J, Jiang, X
Medicine. 2020;(18):e19542
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BACKGROUND Data of non-vitamin K antagonist oral anticoagulants (NOACs) in current management of atrial fibrillation (AF) are predominantly derived from North American and European regions. However, the effects of NOACs for stroke prevention in Latin America remain unclear. Therefore, we aimed to compare the efficacy and safety of NOACs with warfarin in Latin American patients with AF. METHODS The PubMed and Embase databases were systematically searched until July 12, 2019 for applicable randomized clinical trials. The risk ratios (RRs) and 95% confidence intervals (CIs) were pooled using a random-effects model. RESULTS Four trials involving 8943 Latin American patients were included in this meta-analysis. In anticoagulated patients with AF, Latin American patients had higher rates of stroke or systemic embolism and all-cause death compared with non-Latin American subjects. Compared with warfarin use, the use of NOACs was significantly associated with reduced risks of stroke or systemic embolism, major bleeding, intracranial bleeding, and any bleeding in Latin American patients. There were no significant differences in the risks of ischemic stroke, all-cause death, and gastrointestinal bleeding between Latin and non-Latin American groups. All the interactions between Latin and non-Latin American groups about efficacy and safety outcomes of NOACs compared with warfarin were non-significant (all Pinteraction > .05). CONCLUSIONS Our meta-analysis suggested that the use of NOACs was at least non-inferior to warfarin use for stroke prevention in Latin American patients with AF.
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Cardiovascular- and Bleeding-Related Hospitalization Rates With Edoxaban Versus Warfarin in Patients With Atrial Fibrillation Based on Results of the ENGAGE AF-TIMI 48 Trial.
Vilain, K, Li, H, Kwong, WJ, Antman, EM, Ruff, CT, Braunwald, E, Cohen, DJ, Giugliano, RP, Magnuson, EA, ,
Circulation. Cardiovascular quality and outcomes. 2020;(11):e006511
Abstract
Background The ENGAGE AF-TIMI 48 trial (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48) demonstrated noninferiority of once-daily 60 mg (30 mg dose-reduced) edoxaban compared with warfarin for prevention of stroke/systemic embolism in patients with atrial fibrillation. No previous analysis has explored the impact of treatment with edoxaban versus warfarin on rates of hospitalizations. Methods Detailed healthcare resource utilization data from ENGAGE AF-TIMI 48 for the 14 024 randomized patients who received at least one dose of study drug were used to compare the rates of bleeding- and cardiovascular-related hospitalizations for edoxaban versus warfarin. Hospitalization rates were calculated for each treatment group, and relative rates were estimated using Poisson regression. The influence of patient characteristics on the impact of edoxaban versus warfarin was evaluated through the inclusion of interaction terms. Results The overall rate of cardiovascular- or bleeding-related hospitalization was significantly lower for edoxaban than warfarin (relative rate [RR], 0.91 [95% CI, 0.85-0.97], P=0.003). Rates of hospitalizations for cardiovascular reasons (RR, 0.91 [95% CI, 0.85-0.97], P=0.004), stroke (RR, 0.80 [95% CI, 0.72-0.88], P<0.0001), and for each stroke subtype (ischemic: RR, 0.89 [95% CI, 0.81-0.99], P=0.03; hemorrhagic: RR, 0.60 [95% CI, 0.54-0.68], P<0.0001) were also lower for edoxaban. Notably, significantly greater reductions with edoxaban versus warfarin were seen for ischemic stroke-related hospitalizations in vitamin K antagonist naive patients and patients with CHADS2 scores 4 to 6, previous stroke or transient ischemic attack, age ≥75, and no previous coronary artery disease. For nonstroke bleeding-related hospitalizations, greater reductions with edoxaban were seen in vitamin K antagonist naive patients, patients with CHADS2 scores 4 to 6, and patients with moderate renal dysfunction. Conclusions Edoxaban 60 mg (30 mg dose-reduced) was associated with a significantly lower overall rate of cardiovascular- or bleeding-related hospitalization and significant reductions in the subcategories of cardiovascular-related, stroke-related, bleed-related, and nonstroke cardiovascular-related hospitalizations, when compared with warfarin. These results suggest the potential for cost offsets with edoxaban, with even greater reductions in higher-risk patients. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00781391.
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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.
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Safety and Efficacy of Minimally Interrupted Dabigatran vs Uninterrupted Warfarin Therapy in Adults Undergoing Atrial Fibrillation Catheter Ablation: A Randomized Clinical Trial.
Nogami, A, Harada, T, Sekiguchi, Y, Otani, R, Yoshida, Y, Yoshida, K, Nakano, Y, Nuruki, N, Nakahara, S, Goya, M, et al
JAMA network open. 2019;(4):e191994
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IMPORTANCE Uninterrupted dabigatran therapy reduces stroke risk in patients with nonvalvular atrial fibrillation (NVAF) undergoing ablation and is associated with a lower bleeding risk than uninterrupted warfarin therapy. Minimally interrupted direct oral anticoagulant therapy is widely used, but data from controlled studies are insufficient. OBJECTIVE To compare the safety and efficacy of minimally interrupted dabigatran vs uninterrupted warfarin therapy in patients undergoing catheter ablation for NVAF. DESIGN, SETTING, AND PARTICIPANTS The ABRIDGE-J (ABlation peRIoperative DabiGatran in use Envisioning in Japan) trial is a open-label, randomized clinical trial performed in 28 Japanese treatment centers. A total of 504 patients scheduled for NVAF ablation were enrolled; 500 were randomized to the study treatments; 499 received at least 1 dose of dabigatran etexilate (n = 248) or warfarin potassium (n = 251); and 442 underwent ablation (220 in the dabigatran group and 222 in the warfarin group). Data were collected from May 1, 2014, through September 14, 2015, and analyzed from March 7, 2017, through January 28, 2019. INTERVENTIONS Appropriate dose anticoagulation was administered 4 weeks before and at least 3 months after ablation in all patients. Dabigatran therapy was interrupted before catheter ablation (holding of 1-2 doses) and resumed after ablation. MAIN OUTCOMES AND MEASURES Primary end points were the incidence of embolism during the perioperative period and atrial thrombus just before the ablation. The main secondary end point was the incidence of major bleeding events until 3 months after ablation. RESULTS Of the 442 patients who underwent ablation, 74.9% were men and the median age was 66 years (interquartile range, 59-71 years). Before ablation, 1 cerebral infarction and 1 thrombus in the left atrium occurred in the warfarin group, but no events occurred in the interrupted dabigatran group. After ablation, the mean (SD) incidence of major bleeding events was significantly lower with dabigatran (3 patients [1.4% {0.8%}; 95% CI, 0.4%-4.2%]) vs warfarin (11 patients [5.0% {1.5%}; 95% CI, 2.8%-8.8%]; P = .03). No thromboembolic events occurred after ablation in the dabigatran group; 1 (0.5%) occurred in the warfarin group. CONCLUSIONS AND RELEVANCE In patients undergoing ablation for NVAF, anticoagulation with minimally interrupted dabigatran therapy did not increase thromboembolic events and was associated with fewer bleeding complications than uninterrupted warfarin therapy. TRIAL REGISTRATION umin.ac.jp Identifier: UMIN000013129.
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Comparison of Aspirin and Naoxintong Capsule () with Adjusted-Dose Warfarin in Elderly Patients with High-Risk of Non-Valvular Atrial Fibrillation and Genetic Variants of Vitamin K Epoxide Reductase.
Wang, H, Zhou, XK, Zheng, LF, Wu, XY, Chen, H
Chinese journal of integrative medicine. 2018;(4):247-253
Abstract
OBJECTIVE To compared the therapeutic effect of a Chinese patent medicine Naoxintong Capsule (, NXT) and aspirin with adjusted-dose warfarin in Chinese elderly patients (over 65 years) with nonvalvular atrial fibrillation (NVAF) and genetic variants of vitamin K epoxide reductase (VKORC1), who are at high-risk of thromboembolism. METHODS A total of 151 patients, with NVAF and AA genotype of VKORC1-1639 (a sensitive genotype to warfarin) and a CHA2DS2-VASc clinical risk score of 2 or above, were chosen for this study. Patients were randomized into two groups and orally treated with a combination of aspirin (100 mg/day) and NXT (1.6 g thrice a day) or adjusted-dose warfarin [international normalized ratio 2.0-3.0). The primary end points including ischemic stroke and death as well as the secondary end points including hemorrhage events were followed up for at least 1 year. RESULTS Baseline clinical data and the rates of primary end points were similar between groups. However, the rate of serious bleeding (secondary event) in the combination therapy group was lower than that in the adjusted-dose warfarin group (0% vs. 7.9%, odds ratio: 0.921, 95% confidence interval: 0.862-0.984, P=0.028). CONCLUSIONS Aspirin combined with NXT and warfarin displayed comparable rates of primary end point including ischemic stroke and all-cause death during the 1-year follow-up. However, as compared with warfarin, the combination therapy reduced the rate of serious bleeding. Therefore, aspirin combined with NXT might provide an alternative pharmacotherapy in preventing ischemic stroke for elderly patients with NAVF who cannot tolerate warfarin. (No. ChiCTR-TRC-13003596).