The clinical efficacy of dabigatran etexilate for preventing stroke in atrial fibrillation patients.
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SUBMITTER: Ellis CR
PROVIDER: S-EPMC3711881 | biostudies-literature | 2013
REPOSITORIES: biostudies-literature
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The clinical efficacy of dabigatran etexilate for preventing stroke in atrial fibrillation patients.
Ellis Christopher R CR Kaiser Daniel W DW
Vascular health and risk management 20130709
The use of novel oral anticoagulants (NOACs) for stroke and systemic embolism prevention in the setting of specifically non valvular atrial fibrillation has provided clinicians with a realistic treatment alternative to the traditional dose-adjusted, warfarin-based anticoagulation that is targeted to a therapeutic international normalized ratio range of 2.0-3.0. We discuss the use of dabigatran in the setting of mechanical heart valves, atrial fibrillation or left atrial catheter ablation procedu ...[more]
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Project description:Atrial fibrillation (AF) is associated with an increased risk of thromboembolism, and is the most prevalent factor for cardioembolic stroke. Vitamin K antagonists (VKAs) have been the standard of care for stroke prevention in patients with AF since the early 1990s. They are very effective for the prevention of cardioembolic stroke, but are limited by factors such as drug-drug interactions, food interactions, slow onset and offset of action, haemorrhage and need for routine anticoagulation monitoring to maintain a therapeutic international normalised ratio (INR). Multiple new oral anticoagulants have been developed as potential replacements for VKAs for stroke prevention in AF. Most are small synthetic molecules that target thrombin (e.g. dabigatran etexilate) or factor Xa (e.g. rivaroxaban, apixaban, edoxaban, betrixaban, YM150). These drugs have predictable pharmacokinetics that allow fixed dosing without routine laboratory monitoring. Dabigatran etexilate, the first of these new oral anticoagulants to be approved by the United States Food and Drug Administration and the European Medicines Agency for stroke prevention in patients with non-valvular AF, represents an effective and safe alternative to VKAs. Under the auspices of the Regional Anticoagulation Working Group, a multidisciplinary group of experts in thrombosis and haemostasis from Central and Eastern Europe, an expert panel with expertise in AF convened to discuss practical, clinically important issues related to the long-term use of dabigatran for stroke prevention in non-valvular AF. The practical information reviewed in this article will help clinicians make appropriate use of this new therapeutic option in daily clinical practice.
| S-EPMC3712459 | biostudies-literature
Project description:ObjectiveTo assess the cost-effectiveness of dabigatran etexilate, a new oral anticoagulant, versus warfarin and other alternatives for the prevention of stroke and systemic embolism in UK patients with atrial fibrillation (AF).MethodsA Markov model estimated the cost-effectiveness of dabigatran etexilate versus warfarin, aspirin or no therapy. Two patient cohorts with AF (starting age of <80 and ?80 years) were considered separately, in line with the UK labelled indication. Modelled outcomes over a lifetime horizon included clinical events, quality-adjusted life years (QALYs), total costs and incremental cost-effectiveness ratios (ICERs).ResultsPatients treated with dabigatran etexilate experienced fewer ischaemic strokes (3.74 dabigatran etexilate vs 3.97 warfarin) and fewer combined intracranial haemorrhages and haemorrhagic strokes (0.43 dabigatran etexilate vs 0.99 warfarin) per 100 patient-years. Larger differences were observed comparing dabigatran etexilate with aspirin or no therapy. For patients initiating treatment at ages <80 and ?80 years, the ICERs for dabigatran etexilate were £4831 and £7090/QALY gained versus warfarin with a probability of cost-effectiveness at £20?000/QALY gained of 98% and 63%, respectively. For the patient cohort starting treatment at ages <80 years, the ICER versus aspirin was £3457/QALY gained and dabigatran etexilate was dominant (ie, was less costly and more effective) compared with no therapy. These results were robust in sensitivity analyses.ConclusionsThis economic evaluation suggests that the use of dabigatran etexilate as a first-line treatment for the prevention of stroke and systemic embolism is likely to be cost-effective in eligible UK patients with AF.
| S-EPMC3308473 | biostudies-literature
Project description:We aimed to develop a pharmacokinetic (PK) and pharmacodynamic (PD) model from healthy Chinese subjects and real-world non-valvular atrial fibrillation (NVAF) patients. We also investigated meaningful intrinsic and extrinsic factors and related biomarkers for bleeding events. We characterized the integrated PK/PD models based on rich PK/PD data [dabigatran concentration, activated partial thromboplastin time (APTT), prothrombin time (PT), and anti-factor IIa (anti-FIIa) activity] from 118 healthy volunteers and sparse PD data [APTT, PT, and anti-FIIa] from 167 patients with NVAF after verifying the model extrapolation performance. We also documented the correlations between PD biomarkers and clinically relevant bleeding events over one year. Next, we used the final integrated PK/PD model (a two-compartment, linear model with first-order absorption) to evaluate the influence of dosage and individual covariates on PD parameters. The age, high-density liptein cholesterol (HDL-C), and creatinine clearance (CrCL) improved the PK model fit. The linear direct-effects PD model described the correlation between APTT, PT, and anti-FIIa and plasma concentration. CrCL improved the PD model fit. Anti-FIIa was more sensitive to the increase in dabigatran exposure than APTT and PT in the PD model. Therefore, fixed dabigatran doses could be prescribed for patients with NVAF without adjusting for age and HDL-C. We observed an elevated bleeding tendency with higher peak and trough values of APTT, PT, and anti-FIIa. Randomized studies should be performed to evaluate the efficacy and safety of low-dose dabigatran in Chinese patients with NVAF.
| S-EPMC9650305 | biostudies-literature
Project description:Background Clinical significance of dosing dabigatran with different estimates of renal function for treatment of atrial fibrillation (AF) is unknown. Renal function is routinely estimated by the chronic kidney disease epidemiology initiative equation (CKD-EPI) and used to guide dosing. The aim of this study was to investigate the risk of adverse outcomes for patients with AF when different estimators of renal function are used. Material and Methods AF patient data were extracted from national administrative databases. Renal function was estimated using Cockcroft-Gault, CKD-EPI, and CKD-EPI adjusted for body surface area (CKD-EPI-BSA). Outcomes of cerebrovascular accident (CVA), systemic embolism (SE), and hemorrhage were extracted. Results In total, 2,425 patients were identified, of which there were hospitalizations for 138 (5.7%) hemorrhagic events, 45 (1.9%) CVA/SE, and 33 (1.4%) unspecified CVA. The level of agreement between Cockcroft-Gault with CKD-EPI and CKD-EPI-BSA yielded a weighted kappa statistic of 0.47 and 0.71, respectively. CKD-EPI and CKD-EPI-BSA significantly overestimated renal function in elderly patients resulting in higher recommended doses compared with Cockcroft-Gault. The hazard ratio for a hemorrhagic event was 2.32 (95% confidence interval, 1.22-4.42; p = 0.01) when a high dose was given compared with normal dose, based on Cockcroft-Gault. Conclusion Both CKD-EPI and CKD-EPI-BSA equations significantly overestimated renal function in the elderly population compared with the Cockcroft-Gault equation. This may lead to dose selection errors for dabigatran, particularly for those with severe impairment, increasing the risk of adverse outcome. Hence, CKD-EPI and CKD-EPI-BSA equations should not be substituted for the Cockcroft-Gault equation in the elderly for the purpose of renal dosage adjustments.
| S-EPMC6524914 | biostudies-literature
Project description:Atrial fibrillation (AF) is a major risk factor for cardioembolic stroke. Anticoagulant drugs are effective in preventing AF-related stroke. However, the high frequency of anticoagulant-associated major bleeding is a major concern particularly when antiplatelet treatment is simultaneously administered. Here, microarray analysis in peripheral blood cells in eight patients with AF and stroke and eight AF subjects without stroke identified a stroke related gene expression pattern. HSPA1B, which encodes for heat-shock protein 70 kDa (Hsp70), was the most differentially expressed gene. This gene was downregulated in stroke subjects, a finding confirmed further in an independent AF cohort of 200 individuals. Hsp70 knock-out (KO) mice subjected to different thrombotic challenges developed thrombosis significantly earlier than their wild-type (WT) counterparts. In WT mice, Hsp70 inducers (TRC051384, or tubastatin A) delayed thrombus formation. Remarkably, Hsp70 inducers did not increase the bleeding risk even when aspirin was concomitantly administered. Hsp70 induction was associated with an increased vascular thrombomodulin expression, higher circulating levels of activated protein C (APC) upon thrombotic stimulus and increased protection against endothelial apoptosis. Thus, Hsp70 induction is a novel approach to delay thrombus formation with minimal bleeding risk, being especially promising in situations where there is a major bleeding hazard. Microarray analysis in peripheral blood cells includes eight patients with AF and stroke and eight AF subjects without stroke
2016-04-01 | E-GEOD-66724 | biostudies-arrayexpress
Project description:Dabigatran is an oral anticoagulant that is increasingly used for atrial fibrillation (AF). Presently, many authorities state that routine laboratory coagulation monitoring is not required. However, data have recently been published demonstrating that higher trough plasma dabigatran concentrations are associated with lower thromboembolic and higher haemorrhagic event rates. Using these data, we simulate a range of AF patients with varying risks for these events and derive a target range of trough plasma dabigatran concentrations (30-130 μg l(-1) ). Finally, we propose that a conventional screening coagulation assay, the thrombin time (TT), can be used to discern whether or not patients are within this range of dabigatran concentrations.
| S-EPMC4243910 | biostudies-literature
Project description:Atrial fibrillation (AF) is a major risk factor for cardioembolic stroke. Anticoagulant drugs are effective in preventing AF-related stroke. However, the high frequency of anticoagulant-associated major bleeding is a major concern particularly when antiplatelet treatment is simultaneously administered. Here, microarray analysis in peripheral blood cells in eight patients with AF and stroke and eight AF subjects without stroke identified a stroke related gene expression pattern. HSPA1B, which encodes for heat-shock protein 70 kDa (Hsp70), was the most differentially expressed gene. This gene was downregulated in stroke subjects, a finding confirmed further in an independent AF cohort of 200 individuals. Hsp70 knock-out (KO) mice subjected to different thrombotic challenges developed thrombosis significantly earlier than their wild-type (WT) counterparts. In WT mice, Hsp70 inducers (TRC051384, or tubastatin A) delayed thrombus formation. Remarkably, Hsp70 inducers did not increase the bleeding risk even when aspirin was concomitantly administered. Hsp70 induction was associated with an increased vascular thrombomodulin expression, higher circulating levels of activated protein C (APC) upon thrombotic stimulus and increased protection against endothelial apoptosis. Thus, Hsp70 induction is a novel approach to delay thrombus formation with minimal bleeding risk, being especially promising in situations where there is a major bleeding hazard.
2016-04-01 | GSE66724 | GEO
Project description:Objective: Due to the clinical complexity of warfarin, novel oral anticoagulation (NOAC) has been a feasible and safe alternative anticoagulant approach during left atrial appendage closure (LAAC). This study was designed to compare the efficacy and safety of rivaroxaban and dabigatran for nonvalvular atrial fibrillation patients undergoing percutaneous LAAC. Methods: One single and prospective cohort study was performed among patients who received anticoagulation with dabigatran or rivaroxaban. All patients were medicated with a 3-month course of NOAC to facilitate device endothelialization, followed by dual antiplatelet therapy until 6 months, then lifelong aspirin after discharge. Repeated transesophageal echocardiography was scheduled to evaluate thrombosis formation on occluders and thrombus dissolution ability. Results: A total of 262 consecutive patients were initially enrolled. A final number of 250 patients were analyzed; two patients were excluded due to procedure failure and 10 patients had a loss of follow-up; 97 were from the dabigatran group and 153 from the rivaroxaban group. Three patients (1.9%) in the rivaroxaban group and eight (8.2%) in the dabigatran group were experiencing device-related thrombosis (DRT) events during follow-ups. Cumulative Kaplan-Meier estimates showed that the incidence of DRT was lower under rivaroxaban medication during the 6-month follow-ups (p = 0.038*, OR = 3.843, 95%CI: 0.991-14.836). The transesophageal echocardiography (TEE) results showed that the average length and width of DRT in the rivaroxaban group was significantly lower compared with that in the dabigatran group (2.16 vs. 1.60 mm, p = 0.017*, and 1.71 vs. 1.30 mm, p = 0.003*, respectively). The thrombosis dissolved after the switch from dabigatran or rivaroxaban to warfarin within the target range, represented by the average length and width of thrombus with the cooperation of secondary TEE for the dabigatran and rivaroxaban groups (0.64 vs. 0.40 mm, p = 0.206, and 0.43 vs. 0.27 mm, p = 0.082, respectively). No significant difference was found between the two groups with respect to the levels of coagulation parameters, cardiac function, and bleeding events. Conclusion: Compared to dabigatran, post-procedural rivaroxaban anticoagulation might be advantageous in preventing DRT complications expected after LAAC, without increasing the risk of hemorrhage.
| S-EPMC8249758 | biostudies-literature
Project description:In the title compound, C34H41N7O5·4H2O (systematic name: ethyl 3-{[2-({4-[(Z)-amino-(hexyl-oxycarbonyl-imino)-meth-yl]anilino}meth-yl)-1-meth-yl-benzimidazole-5-carbon-yl]pyridin-2-yl-amino}-propano-ate tetra-hydrate), the benzene and pyridine rings form dihedral angles of 5.4 (1) and 43.8 (1)°, respectively, with the benzimidazole mean plane. The terminal butyl group is disordered over two conformations in a 0.756 (10):0.244 (10) ratio. There is an intramolecular N-H⋯O hydrogen bond present. In the crystal, the water mol-ecules are involved in the formation of O-H⋯O, O-H⋯N and N-H⋯O hydrogen bonds, which link the components into layers parallel to the ab plane.
| S-EPMC3588980 | biostudies-literature
Project description:ObjectivesTo determine the incremental net health benefits of dabigatran etexilate 110 mg and 150 mg twice daily and warfarin in patients with non-valvular atrial fibrillation and to estimate the cost effectiveness of dabigatran in the United Kingdom.DesignQuantitative benefit-harm and economic analyses using a discrete event simulation model to extrapolate the findings of the RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) study to a lifetime horizon.SettingUK National Health Service. Population Cohorts of 50,000 simulated patients at moderate to high risk of stroke with a mean baseline CHADS(2) (Congestive heart failure, Hypertension, Age ≥ 75 years, Diabetes mellitus, previous Stroke/transient ischaemic attack) score of 2.1.Main outcome measuresQuality adjusted life years (QALYs) gained and incremental cost per QALY of dabigatran compared with warfarin.ResultsCompared with warfarin, low dose and high dose dabigatran were associated with positive incremental net benefits of 0.094 (95% central range -0.083 to 0.267) and 0.146 (-0.029 to 0.322) QALYs. Positive incremental net benefits resulted for high dose dabigatran in 94% of simulations versus warfarin and in 76% of those versus low dose dabigatran. In the economic analysis, high dose dabigatran dominated the low dose, had an incremental cost effectiveness ratio of £23,082 (€26,700; $35,800) per QALY gained versus warfarin, and was more cost effective in patients with a baseline CHADS(2) score of 3 or above. However, at centres that achieved good control of international normalised ratio, such as those in the UK, dabigatran 150 mg was not cost effective, at £42,386 per QALY gained.ConclusionsThis analysis supports regulatory decisions that dabigatran offers a positive benefit to harm ratio when compared with warfarin. However, no subgroup for which dabigatran 110 mg offered any clinical or economic advantage over 150 mg was identified. High dose dabigatran will be cost effective only for patients at increased risk of stroke or for whom international normalised ratio is likely to be less well controlled.
| S-EPMC3204867 | biostudies-literature