Selection Of Oral Anticoagulants Research Articles

Abstract WP183: Clinical Outcome in Cardioembolic Stroke Patients Receiving DOACs versus Warfarin: K-PLUS Registry

Introduction: Relationship between the selection of oral anticoagulants after acute stroke as secondary prevention and clinical outcome is not elucidated. Our aim is to compare clinical outcome in patients receiving direct oral anticoagulants (DOACs) versus warfarin after their stroke. Methods: In the regional stroke registry, K-PLUS, 1,019 consecutive patients with cardioembolic stroke who were prescribed anticoagulants were retrospectively enrolled from April 2011 to May 2016. Patients with premorbid modified Rankin Scale score of 3 or more and those with incomplete clinical data were excluded. The residual 323 patients were divided into 2 groups by their receiving anticoagulants after their stroke: the warfarin group and the DOACs group. Clinical characteristics, length of hospital stay, Functional Independence Measure (FIM) scores on admission and at discharge of rehabilitation hospital, and mean daily FIM gain were compared between the 2 groups. Results: In the 323 patients, median age was 79 (interquartile range: 73-85) years and 176 (54.5%) were men. A total of 146 patients (46.2%) was prescribed DOACs (dabigatran in 15, rivaroxaban in 46, apixaban in 72, and edoxaban in 13). Median age (81 vs. 79 in median, p = .03) and NIHSS score on acute hospital admission (10 in DOACs vs. 17 in warfarin, p < .01) were lower, and length of acute hospital stay was shorter (13 vs. 17 days, p < .01) in the DOACs group than the warfarin group. In rehabilitation hospitals, both FIM score on admission (86 vs. 32, p < .01) and daily FIM gain (0.22 vs. 0.10, p < .01) was significantly higher in the DOACs group. On multivariate analysis, DOACs prescription (odds ratio 1.79; 95% CI, 1.10-2.93) and NIHSS on acute hospital admission (1.04 per 1 point; 1.01-1.08) were correlated with daily FIM gain ≥ 0.15, independent of other factors including age, length of acute hospital stay, and FIM on admission of rehabilitation hospital. Conclusion: Patients receiving DOACs after their cardioembolic stroke might achieve better clinical outcome than those with warfarin.

Evaluation of oral anticoagulants with vitamin K epoxide reductase in its native milieu

AbstractWarfarin, acenocoumarol, phenprocoumon, and fluindione are commonly prescribed oral anticoagulants for the prevention and treatment of thromboembolic disorders. These anticoagulants function by impairing the biosynthesis of active vitamin K–dependent coagulation factors through the inhibition of vitamin K epoxide reductase (VKOR). Genetic variations in VKOR have been closely associated with the resistant phenotype of oral anticoagulation therapy. However, the relative efficacy of these anticoagulants, their mechanisms of action, and their resistance variations among naturally occurring VKOR mutations remain elusive. Here, we explored these questions using our recently established cell-based VKOR activity assay with the endogenous VKOR function ablated. Our results show that the efficacy of these anticoagulants on VKOR inactivation, from most to least, is: acenocoumarol > phenprocoumon > warfarin > fluindione. This is consistent with their effective clinical dosages for stable anticoagulation control. Cell-based functional studies of how each of the 27 naturally occurring VKOR mutations responds to these 4 oral anticoagulants indicate that phenprocoumon has the largest resistance variation (up to 199-fold), whereas the resistance of acenocoumarol varies the least (<14-fold). Cell-based kinetics studies show that fluindione appears to be a competitive inhibitor of VKOR, whereas warfarin is likely to be a mixed-type inhibitor of VKOR. The anticoagulation effect of these oral anticoagulants can be reversed by the administration of a high dose of vitamin K, apparently due to the existence of a different enzyme that can directly reduce vitamin K. These findings provide new insights into the selection of oral anticoagulants, their effective dosage management, and their mechanisms of anticoagulation.

Selection of Oral Anticoagulants in Ischemic Stroke Patients with Nonvalvular Atrial Fibrillation

BackgroundAnticoagulant therapy is indicated for management of ischemic stroke patients with nonvalvular atrial fibrillation. We retrospectively investigated how oral anticoagulants were selected for ischemic stroke patients with nonvalvular atrial fibrillation. MethodsThis study included 297 stroke patients with nonvalvular atrial fibrillation admitted to our hospital between September 2014 and December 2017, and who were subsequently transferred to other institutions or discharged home. Baseline clinical characteristics were compared between patients prescribed warfarin and those prescribed direct-acting oral anticoagulants. ResultsIn total, 280 of 297 (94.3%) patients received oral anticoagulant therapy, including 36 with warfarin, while 244 received direct oral anticoagulants. Age, percentage of heart failure, CHADS2 score before stroke onset, percentage of treatment with warfarin on admission, percentage of feeding tube at hospital discharge, and modified Rankin Scale at hospital discharge were significantly higher in the warfarin group versus the direct oral anticoagulants group, while creatinine clearance was significantly higher in the direct oral anticoagulant group. By multiple logistic regression, taking warfarin at admission and higher modified Rankin Scale at hospital discharge were associated with warfarin selection, while higher creatinine clearance was associated with direct oral anticoagulant selection (warfarin: odds ratio [OR] 7.10 [95% confidence interval {CI} 2.83-17.81]; modified Rankin Scale at hospital discharge: [OR] 1.47 [95% {CI} 1.06-2.04]; creatinine clearance: [OR] .97 [95% {CI} .95-.99]). ConclusionsSelection of oral anticoagulants in acute ischemic stroke patients with nonvalvular atrial fibrillation was influenced by warfarin use at admission, clinical severity at hospital discharge, and renal function.

2018 KHRS Guidelines for Stroke Prevention Therapy in Korean Patients with Nonvalvular Atrial Fibrillation

Atrial fibrillation (AF) is the most common cardiac abnormality associated with ischemic stroke. Anticoagulant therapy plays an important role in the prevention of stroke associated with AF. Risk stratification and selection of oral anticoagulants in patients with AF are usually performed according to international guidelines from Europe or the United States of America. However, pivotal trials enrolled only a small number of Asian subjects, limiting the application of international guidelines to Korean patients with AF. The Korean Heart Rhythm Society organized a Korean AF Management Guideline Committee and analyzed all available studies regarding the management of AF, including studies on Korean patients. Expert consensus or guidelines for the optimal management of Korean patients with AF were achieved after a systematic review with intensive discussion. This article provides general principles for appropriate risk stratification and selection of anticoagulation therapy in Korean patients with AF. (Korean J Med 2018;93:87-109)

2018 KHRS Expert Consensus Recommendation for Oral Anticoagulants Choice and Appropriate Doses: Specific Situation and High Risk Patients

Oral anticoagulants (OAC) are necessary to prevent thromboembolism in patients with atrial fibrillation (AF). OACs used in Korea are composed of warfarin and non-vitamin K antagonist OAC. Risk stratification and selection of OACs in patients with AF is usually performed by international guidelines for AF management. However, these guidelines do not always reflect the unique characteristics of AF patients in Korea as they were established based on a small portion of the Asian population and, therefore, have limited application to Korean patients. In addition, under certain conditions, the choice of OACs and doses according to the international guidelines are unsuitable for Korean AF patients. Recently, robust clinical data of Korean AF patients have become available. The Korean AF Management Guideline Committee, as part of the Korean Heart Rhythm Society, analyzed all available studies regarding management of AF including those focusing on Korean patients. Expert consensus and guidelines for optimal management of AF patients in Korea were established following systematic reviews and intensive discussions. This article provides the appropriate choice of OACs and dose for management of Korean AF patients with various clinical conditions. (Korean J Med 2018;93:110-132)

ORAL ANTICOAGULANT PRESCRIPTION ANALYSIS FOR UTILISATION PATTERN AMONG IN-PATIENTS AT A TERTIARY CARE HOSPITAL

Objective: Selection of oral anticoagulants (OACs) in patients with thromboembolic diseases is complex and equivocal in nature, owing majorly to the non-adherence to standard clinical guidelines. Moreover, there is a scarcity of data on utilisation pattern of OACs in Indian population. Our primary objective was to analyse the prescribing pattern of OACs among in-patients with thromboembolic disorders. The secondary objective was to determine the significant predictors that affect their utilisation pattern.Methods: This prospective observational study examined the clinical data over 6 mo from in-patients on oral anticoagulation with warfarin and acenocoumarol. Patients were recruited into 2 study groups: coronary artery disease (CAD) and non-CAD to analyse the prescription pattern. Potential predictors of utilisation pattern were evaluated for significance with logistic regression analysis for CAD group.Results: Prescription analysis highlights preference of acenocoumarol (72.4%) over warfarin among 232 in-patients in the study. Lack of achievement of target international normalised ratio (INR) levels was noticed in 74.2% of the study population. 57.8% of cases belonged to CAD group (males 76.7%; mean age 59.4±13.5 y). Valvular heart disease (VHD) was the significant predictor (p =0.001) of warfarin utilisation among CAD patients while male gender, heart failure (HF) and arrhythmia were significant for acenocoumarol.Conclusion: Predominance of age&lt;60 y and male gender was observed in the study. Acenocoumarol was preferred over warfarin in all the in-patient departments. VHD, male gender, HF and arrhythmia significantly affected the OAC utilisation.

Factors associated with non–vitamin K antagonist oral anticoagulants for stroke prevention in patients with new-onset atrial fibrillation: Results from the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II (ORBIT-AF II)

Several non-vitamin K antagonist oral anticoagulant (NOAC) alternatives to warfarin are available for stroke prevention in atrial fibrillation (AF). We aimed to describe the factors associated with selection of NOACs versus warfarin in patients with new onset AF. The ORBIT-AF II study is a national, US, prospective, observational, cohort study of anticoagulation treatment in patients with AF receiving NOACs or warfarin in the United States from 2013 to 2016. We measured factors associated with oral anticoagulant selection in 4,670 patients recently diagnosed with AF. At baseline, 1,169 (25%) patients were started on warfarin and 3,501 (75%) on NOACs: of these latter, 259 (6%) were started on dabigatran, 1858 (40%) on rivaroxaban, and 1384 (30%) on apixaban. Those receiving NOACs were slightly younger patients (median age 71 vs 72, P<.0001); were less likely to have prior stroke (5.3% vs 8.6%; P<.0001) or prior bleeding (2.7% vs 4.4%; P=.005); had better kidney function (mean estimated glomerular filtration rate 91 mL/min vs 80 mL/min, P<.0001); and had fewer patients at high stroke risk (CHA2DS2-VASc score [Congestive heart failure, Hypertension, Age ≥75years, Diabetes mellitus, Prior stroke, transient ischemic attack {TIA}, or thromboembolism,Vascular disease, Age 65-74years, Sex category {female}] ≥2 in 86% vs 93%; P<.0001). In multivariable analysis, factors associated with NOAC selection versus warfarin included renal function, prior stroke or valve replacement, rhythm control AF management strategy, treatment by a cardiologist, and higher patient education level. In contemporary clinical practice, up to three-fourths of patients with new-onset AF are now initially treated with a NOAC for stroke prevention. Those selected for NOAC treatment had lower stroke and bleeding risk profiles, were more likely treated by cardiologists, and had higher socioeconomic status. clinicaltrials.gov Identifier: NCT01701817.

Drug Therapies for Stroke Prevention in Atrial Fibrillation: An Historical Perspective.

Oral anticoagulants are effective in minimizing stroke and systemic embolism in patients with atrial fibrillation at risk. All have a high degree of efficacy and acceptable safety records. Drug selection should be made on an individual basis. The most important thing is to make the selection. There are many factors to consider in the selection of oral anticoagulants. The new oral anticoagulants offer a measure of improvement over the many limits of warfarin; however, well-managed warfarin is an acceptable and inexpensive option. The efficacy of aspirin is questionable at best, deserving its almost complete disappearance from the guidelines.

A Guidance Pathway for the Selection of Novel Anticoagulants in the Treatment of Atrial Fibrillation

Oral anticoagulation with vitamin K antagonists has served as the primary treatment for the prevention of stroke and systemic embolization in patients with atrial fibrillation (AF) for decades. Over the past several years, multiple novel oral anticoagulants targeting key mediators of coagulation, including thrombin and factor Xa, have been developed. Specifically, agents targeting thrombin (dabigatran) and factor Xa (apixaban and rivaroxaban) have either reached late stages of clinical development (apixaban) or have received approval (dabigatran, rivaroxaban) by the US Food and Drug Administration for use in patients with nonvalvular AF. The promising results derived from large-scale clinical trials with these agents compared to warfarin expand the available therapeutic options for the prevention of stroke and systemic embolization in this rapidly increasing patient population. Here we present a general guidance pathway for the initiation and selection of oral anticoagulants in patients with AF.