Yes / Patients with non-valvular atrial fibrillation (AF) requiring oral anticoagulants (OAC) for stroke prevention currently have a choice of five OACs. A systematic review was undertaken to explore if patients with AF requiring an OAC for stroke prevention are involved in decision-making.

Yes / Background and Objective In England, the uptake of direct oral anticoagulants (DOACs) for stroke prevention in atrial fbrillation has been slow and varied across diferent Clinical Commissioning Groups (CCGs). This study aimed to profle the prescribing of oral anticoagulants for stroke prevention in patients with atrial fbrillation over 3 years in a CCG without restrictions to DOACs use to understand more about organisational and/or individual barriers to the early uptake of DOACs. Methods Data were collected from nine general practices between 1 April 2012 and 31 March 2015 of patients who were initiated on the oral anticoagulant therapy. Data were analysed descriptively and with independent Student’s t test and Chi square test to explore if there was an association between type of oral anticoagulant initiated and sex, age, type of prescriber and prior aspirin use. Results The early uptake of DOACs signifcantly increased over the study period (p<0.0001; medium size efect φc=0.372). There was no statistically signifcant diference between sex or age and type of oral anticoagulant initiated. Primary-care prescribers were responsible for initiating the majority of oral anticoagulants (71%; N=257) and driving the use of DOACs (72%, N=71). Patients switched from aspirin to an oral anticoagulant were more likely to be initiated on warfarin than a DOAC. Conclusions The early use of DOACs, in a CCG without restrictions to their use, was embraced by primary-care prescribers in this particular CCG. / Bayer Pharmaceuticals via an unrestricted educational grant.

No description available.

En France, depuis 2012, les anticoagulants oraux directs (AOD), indiqués dans la prévention des accidents vasculaires cérébraux chez les patients avec fibrillation auriculaire (FA) non valvulaire, sont une alternative aux antivitamines K (AVK) pour lesquels une sous-prescription et un défaut d’observance ont été largement décrits. L’objectif de cette thèse était, dans le cadre du programme de travail du Département études de santé publique de la Caisse nationale de l’Assurance maladie, d’étudier à partir des bases de données médico-administratives (BDMA) françaises l’utilisation et la sécurité du traitement anticoagulant oral (ACO) en situation réelle de soins chez les patients avec FA. Un premier travail a permis de construire un algorithme pour identifier l’indication FA chez les patients débutant un ACO et pour lesquels aucun diagnostic de FA n’était retrouvé dans les BDMA. Un deuxième travail a porté sur l’évaluation de l’adhésion au traitement ACO chez les nouveaux utilisateurs : au cours de l’année suivant l’initiation du traitement, au moins un patient sur trois arrêtait son traitement, dabigatran ou rivaroxaban, et la persistance à ces traitements n’était pas meilleure que celle des AVK. Un troisième travail a décrit une amélioration de la couverture anticoagulante chez les patients avec FA entre 2011 et 2016. Cependant, un patient sur trois était encore sans traitement ACO en 2016 et de potentiels mésusages à l’instauration du traitement AOD ont été identifiés, dont un signal de sous-dosage. Enfin, une analyse en symétrie de séquences a suggéré que l’initiation des AOD serait associée à la survenue rare d’atteintes toxiques aiguës du foie et à la survenue plus fréquente de troubles gastrointestinaux. Avec la description de la population et de l’utilisation rejointes des traitements ACO en France chez les patients avec FA, ces résultats encouragent la poursuite de la surveillance des effets indésirables non hémorragiques des AOD et l’amélioration de leur utilisation. / Direct oral anticoagulants (DOAC) were gradually introduced since 2012 in France for stroke and systemic embolism prevention in patients with nonvalvular atrial fibrillation (AF), as a more convenient alternative to vitamin K antagonists (VKA) for which underprescribing and high rates of discontinuation have been frequently reported. As part of the work programme of the Department of Studies in Public Health, French National Health Insurance, the aim of this dissertation was to assess the patterns of use and safety of oral anticoagulant (OAC) therapy in real-life setting using the French healthcare databases. First, an algorithm was developed to identify AF in outpatients initiating OAC and for whom no diagnosis of AF was found in the French claims data. Second, 1-year dabigatran and rivaroxaban adherence rates were estimated in nonvalvular AF patients and 1-year non-persistence rates were compared versus VKA. At least 1 in 3 dabigatran or rivaroxaban new users was found to be non-adherent to treatment. Treatment persistence among dabigatran or rivaroxaban new users was not found to be better versus VKA therapy. Third, OAC therapy use was found to have increased following in France between 2011 and 2016 but remained suboptimal with 1 in 3 patients with AF not treated by OAC therapy. Several situations of inappropriate use of DOAC were identified including potential undertreatment by inappropriate dosing. Finally, a sequence symmetry analysis suggested that DOAC therapy is associated with rare but severe liver injury and more frequent gastrointestinal disorders. A low risk of kidney injury with DOAC therapy can also not be excluded. These findings advocate further investigation of the potential risk of DOAC underdosing at initiation and the continuous monitoring of the non-bleeding adverse events of DOAC therapy.

<p>Diss. (sammanfattning) Umeå : Umeå universitet, 2003</p> / digitalisering@umu

Les microhémorragies cérébrales (MHC) sont caractérisées par une rupture des petits vaisseaux intracérébraux, conduisant à des épanchements sanguins d’un diamètre inférieur à 5 mm chez l’Homme, et considérées sans gravité. Malgré leur dimension microscopique et leur caractère silencieux, elles sont de plus en plus prises en compte par les cliniciens car elles peuvent représenter une fragilité vasculaire et refléter la sévérité d’une pathologie neurovasculaire sous-jacente. Leur toxicité pour le tissu cérébral est souvent spéculée mais n’a jamais été démontrée, laissant planer le doute à propos de leur impact potentiel sur l’apparition ou la précipitation d’un déclin cognitif. De plus, il est difficile de connaitre les effets propres des MHC car elles sont souvent associées à une pathologie dont les caractéristiques viennent influencer les effets observés. C’est dans ce contexte que nous avons développé une nouvelle méthode d’induction de MHC disséminées chez la souris saine. En plus de l’étude de l’impact de ces lésions au niveau histologique et comportemental à court et à long terme, nous avons évalué l’influence de facteurs de risque vasculaires (par un traitement anticoagulant oral) et métaboliques (par le biais d’une alimentation riche en gras) sur leur sévérité. Nos investigations ont permis de montrer que la présence de MHC disséminées dans un contexte sain est responsable de l’apparition progressive d’une altération de la mémoire de reconnaissance visuelle chez la souris. L’ajout d’un traitement anticoagulant oral augmente la sévérité des lésions mais qui restent cependant silencieuses à court terme, hormis pour la warfarine responsable de transformations hémorragiques mortelles. De même, la présence de troubles métaboliques n’a que peu d’impact sur la gravité des poids microhémorragiques observés. Dans les deux cas, la présence de MHC ne provoque pas de précipitation ou d’aggravation du déclin cognitif induit à long terme. Ainsi, les facteurs de risque vasculaires et métaboliques ne semblent pas avoir d’influence directe sur la toxicité induite par les MHC dans un contexte d’altération cognitive non neurodégénérative. / Cerebral microhemorrhages (CMH) are characterized by the rupture of small intracerebral vessels, leading to blood effusions with a diameter of less than 5 mm in Humans, and considered as asymptomatic. Despite their microscopic size and their silent nature, they are increasingly taken into account by clinicians because they can reflect a vascular fragility and the severity of underlying neurovascular diseases. Their toxicity to the brain tissue is often speculated but has never been demonstrated, raising doubt about their potential impact on the onset or on the evolution of cognitive decline. Moreover, it is difficult to know the specific effects of CMH because they are often associated with a pathology whose characteristics influence the results observed. In this context, we have developed a new method of induction of disseminated CMH in healthy mice. In addition to investigate the histological and behavioral impact of these lesions in the short and in the long term, we assessed the influence of vascular risk factors (through oral anticoagulant treatments) and metabolic disorders (through a high fat diet) on their severity. Our investigations demonstrate that the presence of disseminated CMH in a healthy context induce a progressive impairment of visual recognition memory in mice. The addition of an oral anticoagulant treatment increases the severity of the lesions but they remain silent in the short term, except for the warfarin which provokes fatal hemorrhagic transformations. Similarly, the presence of metabolic disorders has little impact on the severity of microhemorrhagic burdens. In any case, the presence of CMH does not precipitate or aggravate the long-term cognitive decline. Thus, vascular and metabolic risk factors do not appear to have a direct influence on CMH-induced toxicity in a context of non-neurodegenerative cognitive impairment.

Background Treatment of ischemic stroke with recombinant tissue plasminogen activator for intravenous thrombolysis (IVT) must be delivered within a narrow time window after symptom onset. This effective hyperacute treatment can be administered after ruling out active anticoagulation with direct oral anticoagulants (DOACs). Whenever this is impractical, e.g., due to aphasia, plasmatic DOAC levels are measured with a consequent delay in the IVT decision-making process ranging from 30 to 60 minutes of time. This study will test the hypothesis that hyperacute point-of-care assessment of clotting time in the patient's whole blood has sufficient diagnostic accuracy to determine immediately whether stroke patients are pretreated with DOAC. Methods and Design This will be a prospective single-center diagnostic accuracy study in 1,850 consecutive acute ischemic stroke patients at a tertiary stroke center in Saxony, Germany. Presence of active anticoagulation with DOAC will be determined by point-of-care quantification of clotting time via whole blood viscoelastic testing (ClotPro) using Russell venom viper and ecarin assay compared with high-performance liquid chromatography-tandem mass spectrometry as the reference standard. Discussion Viscoelastic point-of-care assessment of clotting time in whole blood might improve swift delivery of time-sensitive hyperacute treatment with IVT in stroke patients.

Implementation and uptake of novel and cost-effective medicines can improve patient health outcomes and healthcare efficiency. However, the relative uptake of new medicines recommended by the National Institute for Health and Care Excellence often lags behind other comparative countries’ health systems. One example is the uptake of direct oral anticoagulants (DOACs) for stroke prevention in atrial fibrillation, which was slow and had a high level of unexplained variation across different health economies in England. This research aimed to explore barriers and enablers to the uptake of DOACs from the perspectives of patients, healthcare professionals, and key stakeholders by conducting systematic and narrative reviews and semi-structured interviews. Data collected from 21 patients, 23 healthcare professionals, and 23 key stakeholders recruited from three different health economies was analysed using the Framework method. The findings identified a range of intersecting factors acting as barriers and/or enablers to the uptake DOACs. While there were a wide range of experiences and views, an agreement between patients and healthcare professionals/key stakeholders on several identified factors was observed. Attributes of the innovation, characteristics of patients and prescribers, local health economy readiness for change, implementation process, and external health system context were suggested as influences. Mapping of the findings to the Diffusion of Innovations in Service Organisations model identified 11 components for a future toolkit development to facilitate uptake of nationally recommended new medicines. This thesis highlighted the role of patients, consideration of all costs associated with new medicines, and compatibility with the health economy’s care model impact on the uptake.

BACKGROUND:Anticoagulation with vitamin K antagonists such as warfarin has historically been used for the long term management of patients with thromboembolic disease. However, these agents have a slow onset of action which requires bridging therapy with heparin and its analogues, which are available only in parenteral route. To overcome these limitations, new oral anticoagulants such as factor Xa inhibitors and direct thrombin inhibitors have been developed. The aim of this article is to systematically review the phase 3 clinical trials of new oral anticoagulants in common medical conditions.METHODS:We searched PubMed (Medline) from January 2007 to February 2013 using "Oral anticoagulants", "New oral anticoagulants", "Randomized controlled trial", "Novel anticoagulants", "Apixaban", "Rivaroxaban", "Edoxaban", "Dabigatran etexilate", "Dabigatran" and a combination of the above terms. The available evidence from the phase 3 RCTs was summarized on the basis of individual drug and the medical conditions categorized into "atrial fibrillation", "acute coronary syndrome", "orthopedic surgery", "venous thromboembolism" and "medically ill patients".RESULTS:Apixaban, rivaroxaban and dabigatran have been found to be either non-inferior or superior to enoxaparin in prophylaxis of venous thromboembolism in knee and hip replacement with similar bleeding risk, superior to warfarin for stroke prevention in atrial fibrillation with significant reduction in the risk of major bleeding, non-inferior to aspirin for reducing cardiovascular death and stroke in acute coronary syndrome with significant increase in the risk of major bleed. Rivaroxaban and dabigatran are also superior to the conventional agents in the management of symptomatic venous thromboembolism. However, compared to enoxaparin, apixaban and rivaroxaban use lead to significantly increased bleeding risk in medically ill patients. Additional studies evaluating the specific reversal agents of these new drugs for the management of life-threatening bleeding or other adverse effects are necessary.CONCLUSION:Considering their pharmacological properties, their efficacy and bleeding complications, the new oral agents offer a net favourable clinical profile in orthopedic surgery, atrial fibrillation, acute coronary syndrome and increase the risk of bleeding in critically ill patients. Further studies are necessary to determine the long term safety and to identify the specific reversal agents of these new drugs.

Introduction : L’amélioration de la pertinence des soins est une priorité nationale. À l’hôpital, elle peut s’appuyer sur la mesure d’indicateurs. L’objectif était de : (i) définir le cadre méthodologique et les enjeux liés au développement, à la validation et à la diffusion d’indicateurs ; (ii) construire une démarche de développement, validation et diffusion d’indicateurs de pertinence des prescriptions d’anticoagulants oraux (ACO) automatisés. Méthodes : La définition du cadre méthodologique et des enjeux a été réalisée à partir de synthèses de la littérature et de travaux exploratoires. La démarche appliquée aux indicateurs d’ACO reposait sur : (i) une revue de littérature pour définir des indicateurs à partir de recommandations européennes ; (ii) un consensus d’experts pour sélectionner des indicateurs utiles et opérationnels ; (iii) le développement prospectif de techniques de recherche de l’information pour construire les indicateurs ; (iv) une étude transversale pour évaluer les performances métrologiques des indicateurs. Résultats : Le cadre méthodologique et les enjeux ont été définis. La démarche appliquée aux indicateurs d’ACO a permis : (i) la définition de 19 indicateurs ; (ii) la sélection de 16 indicateurs utiles et opérationnels ; (iii) le développement de techniques pour construire les indicateurs via un entrepôt de données ; (iv) la proposition de méthodes pour évaluer les performances métrologiques des indicateurs en comparaison à un test de référence. Conclusion : Ces travaux apportent des outils pour développer, valider et diffuser des indicateurs. Les indicateurs les plus performants pourront être utilisés par des établissements de santé européens. / Introduction: Improvement of the appropriateness of care is a national priority. In hospitals, it can rely on the measurement of indicators. The objective was to: (i) define the methodological framework and challenges related to the development, validation and feedback of indicators; (ii) implement an approach for the development, validation and feedback of automated indicators of the appropriateness of oral anticoagulant (OA) prescriptions. Methods: Definition of the methodological framework and challenges has been performed through syntheses of literature data and exploratory works. The approach applied to indicators on OA prescriptions was based on: (i) a literature review to define indicators from European guidelines; (ii) a consensus of experts to select useful and operational indicators; (iii) the prospective development of data search techniques for retrieving information aimed at implementing indicators; (iv) a cross-sectional study to assess the ability of indicators to detect inappropriate OA prescriptions. Results: The methodological framework and challenges have been defined. The approach applied to indicators on OA prescriptions allowed: (i) defining 19 indicators; (ii) selecting 16 useful and operational indicators; (iii) developing techniques for implementing indicators from a data warehouse; (iv) developing methods for assessing the ability of tools to detect inappropriate OA prescriptions in comparison to a reference test. Conclusion: This work provides tools to develop, validate and convey indicators. The most performant indicators to detect inappropriate OA prescriptions may be used by European healthcare institutions.