BACKGROUND: We update recommendations on 12 topics that were in the 9th edition of these guidelines, and address 3 new topics.
METHODS: We generate strong (Grade 1) and weak (Grade 2) recommendations based on high- (Grade A), moderate- (Grade B), and low- (Grade C) quality evidence.
RESULTS: For VTE and no cancer, as long-term anticoagulant therapy, we suggest dabigatran (Grade 2B), rivaroxaban (Grade 2B), apixaban (Grade 2B), or edoxaban (Grade 2B) over vitamin K antagonist (VKA) therapy, and suggest VKA therapy over low-molecular-weight heparin (LMWH; Grade 2C). For VTE and cancer, we suggest LMWH over VKA (Grade 2B), dabigatran (Grade 2C), rivaroxaban (Grade 2C), apixaban (Grade 2C), or edoxaban (Grade 2C). We have not changed recommendations for who should stop anticoagulation at 3 months or receive extended therapy. For VTE treated with anticoagulants, we recommend against an inferior vena cava filter (Grade 1B). For DVT, we suggest not using compression stockings routinely to prevent PTS (Grade 2B). For subsegmental pulmonary embolism and no proximal DVT, we suggest clinical surveillance over anticoagulation with a low risk of recurrent VTE (Grade 2C), and anticoagulation over clinical surveillance with a high risk (Grade 2C). We suggest thrombolytic therapy for pulmonary embolism with hypotension (Grade 2B), and systemic therapy over catheter-directed thrombolysis (Grade 2C). For recurrent VTE on a non-LMWH anticoagulant, we suggest LMWH (Grade 2C); for recurrent VTE on LMWH, we suggest increasing the LMWH dose (Grade 2C).
CONCLUSIONS: Of 54 recommendations included in the 30 statements, 20 were strong and none was based on high-quality evidence, highlighting the need for further research.
Since 2008, the direct-acting oral anticoagulants (DOACs) have expanded the therapeutic options of cardiovascular diseases with recognized clinical and epidemiological impact, such as non-valvular atrial fibrillation (NVAF) and venous thromboembolism (VTE), and also in the preventive setting of orthopedic surgical patients. The large body of evidence, not only from pivotal clinical trials but also from ‘real-world’ postmarketing observational findings (e.g. analytical epidemiological studies and registry data) gathered to date allow for a first attempt at verifying a posteriori whether or not the pharmacological advantages of the DOACs actually translate into therapeutic innovation, with relevant implications for clinicians, regulators and patients. This review aims to synthesize the risk–benefit profile of DOACs in the aforementioned consolidated indications through an ‘evidence summary’ approach gathering the existent evidence-based data, particularly systematic reviews with meta-analyses of randomized controlled trials, as well as observational studies, comparing DOACs with vitamin K antagonists. Clinical evidence will be discussed and compared with major international guidelines to identify whether an update is needed. Controversial clinically relevant safety issues will be also examined in order to highlight current challenges and unsettled questions (e.g. actual bleeding risk in susceptible populations). It is anticipated that the large number of publications on NVAF or VTE (44 systematic reviews with meta-analyses and 12 observational studies retained in our analysis) suggests the potential existence of overlapping studies and calls for common criteria to qualitatively and quantitatively assess discordances, thus guiding future research.
Idiopathic thromboembolic disease presents a high risk of recurrence. There is controversy about the effects of aspirin in reducing this risk after the completion of anticoagulant treatment. Searching in Epistemonikos database, which screens 30 databases, we identified four systematic reviews that together include two randomized trials. We combined the evidence using meta-analysis and generated a summary of findings table following the GRADE approach. We concluded that aspirin administered after having completed anticoagulation reduces the risk of recurrence, probably without importantly increasing the risk of hemorrhage.
CONTEXTE: Cet article porte sur le traitement de la maladie de TEV.
MÉTHODES: Nous avons généré une forte (Grade 1) et la faiblesse des recommandations (Grade 2) Sur la base (Grade A), (Grade B), et les preuves de haute qualité de qualité moyenne à faible qualité (grade C).
RÉSULTATS: Pour thrombose veineuse profonde aiguë ou d'embolie pulmonaire (EP), nous recommandons un traitement initial de l'anticoagulant par voie parentérale (Grade 1B) ou anticoagulation par rivaroxaban. Nous suggérons héparine de bas poids moléculaire (HBPM) ou le fondaparinux sur IV héparine non fractionnée (Grade 2C) ou sous-cutanée d'héparine non fractionnée (Grade 2B). Nous suggérons un traitement thrombolytique pour PE avec hypotension (Grade 2C). Pour TVP proximale ou une EP, nous recommandons un traitement de 3 mois sur des périodes plus courtes (Grade 1B). Pour une première thrombose veineuse profonde proximale ou EP qui est provoquée par une chirurgie ou par un facteur de risque transitoire non chirurgicale, nous recommandons 3 mois de traitement (1b année; Grade 2B si provoquée par un facteur de risque non chirurgicale et le risque faible ou modéré saignements), qui est sans provocation , nous vous proposons un traitement prolongé si le risque de saignement est faible ou modérée (Grade 2B) et nous recommandons 3 mois de traitement si le risque de saignement est élevé (Grade 1B), et qui est associée à un cancer actif, nous recommandons un traitement prolongé (Grade 1B, 2B grade en cas de risque élevé de saignement) et de proposer des HBPM sur les antagonistes de la vitamine K (Grade 2B). Nous suggérons des antagonistes de la vitamine K ou HBPM sur dabigatran ou rivaroxaban (Grade 2B.) Nous suggérons des bas de contention pour éviter le syndrome post-thrombotique (Grade 2B). Pour une thrombose veineuse superficielle, nous vous suggérons fondaparinux prophylactique à dose unique ou HBPM plus aucune anticoagulation (Grade 2B), et suggérons fondaparinux sur HBPM (Niveau 2C).
CONCLUSION: Des recommandations fortes s'appliquent à la plupart des patients, alors que les recommandations faibles sont sensibles aux différences entre les patients, y compris leurs préférences.
INTRODUCTION: Deep venous thrombosis (DVT) or pulmonary embolism may occur in almost 2 in 1000 people each year, with up to 25% of those having a recurrence. Around 5% to 15% of people with untreated DVT may die from pulmonary embolism. Risk factors for DVT include immobility, surgery (particularly orthopaedic), malignancy, pregnancy, older age, and inherited or acquired prothrombotic clotting disorders.
METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments for proximal DVT? What are the effects of treatments for isolated calf DVT? What are the effects of treatments for pulmonary embolism? What are the effects of interventions on oral anticoagulation management in people with thromboembolism? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS: We found 45 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: anticoagulation; compression stockings; low molecular weight heparin (short and long term, once or twice daily, and home treatment); oral anticoagulants (short and long term, high intensity, abrupt discontinuation, and computerised decision support); prolonged duration of anticoagulation; thrombolysis; vena cava filters; and warfarin.
CONTEXTE: La décision d'arrêter l'anticoagulation après un épisode de thrombo-embolie veineuse (TEV) dépend du risque de récidive. Un certain nombre de facteurs de risque abordés récemment qui ne sont pas couramment utilisées en pratique clinique pourrait être utile pour l'identification des patients présentant un faible risque de récidive. OBJECTIFS: L'objectif de cette étude était de déterminer la valeur prédictive négative et le rapport de vraisemblance de l'absence de chacun de ces facteurs chez les patients ayant un ETEV. Les patients et méthodes: Nous avons effectué une revue systématique de la littérature, ou calculées des valeurs prédictives négatives et rapports de vraisemblance, et résume les données probantes disponibles. RÉSULTATS: Un négatif de D-dimères résultat, non-élevée au niveau de facteur VIII et de génération de thrombine non-élevée après l'arrêt du traitement anticoagulant, le sexe féminin et l'emplacement distale peut être utile pour déterminer un faible risque de récidive chez les patients ayant un ETEV. Chacune de ces facteurs est individuellement associée à une valeur prédictive négative de la survie sans récidive dans les 2-3 prochaines années d'environ 90% (avec un risque à priori d'environ 85%), avec les rapports de vraisemblance négatifs entre 0,8 et 0,5. Certains des facteurs de risque pour l'événement VTE (FV Leiden et la mutation de prothrombine) ne sont pas du tout utile pour la prédiction de la non-récurrence. CONCLUSIONS: Aucun des facteurs de risque que nous avons identifiés est assez fort sur son propre pour guider le traitement. Combinaisons de facteurs de risque pourrait être plus utile, mais des données supplémentaires sur l'indépendance de ces facteurs sont nécessaires avant une règle de prédiction peuvent être conçus.
We update recommendations on 12 topics that were in the 9th edition of these guidelines, and address 3 new topics.
METHODS:
We generate strong (Grade 1) and weak (Grade 2) recommendations based on high- (Grade A), moderate- (Grade B), and low- (Grade C) quality evidence.
RESULTS:
For VTE and no cancer, as long-term anticoagulant therapy, we suggest dabigatran (Grade 2B), rivaroxaban (Grade 2B), apixaban (Grade 2B), or edoxaban (Grade 2B) over vitamin K antagonist (VKA) therapy, and suggest VKA therapy over low-molecular-weight heparin (LMWH; Grade 2C). For VTE and cancer, we suggest LMWH over VKA (Grade 2B), dabigatran (Grade 2C), rivaroxaban (Grade 2C), apixaban (Grade 2C), or edoxaban (Grade 2C). We have not changed recommendations for who should stop anticoagulation at 3 months or receive extended therapy. For VTE treated with anticoagulants, we recommend against an inferior vena cava filter (Grade 1B). For DVT, we suggest not using compression stockings routinely to prevent PTS (Grade 2B). For subsegmental pulmonary embolism and no proximal DVT, we suggest clinical surveillance over anticoagulation with a low risk of recurrent VTE (Grade 2C), and anticoagulation over clinical surveillance with a high risk (Grade 2C). We suggest thrombolytic therapy for pulmonary embolism with hypotension (Grade 2B), and systemic therapy over catheter-directed thrombolysis (Grade 2C). For recurrent VTE on a non-LMWH anticoagulant, we suggest LMWH (Grade 2C); for recurrent VTE on LMWH, we suggest increasing the LMWH dose (Grade 2C).
CONCLUSIONS:
Of 54 recommendations included in the 30 statements, 20 were strong and none was based on high-quality evidence, highlighting the need for further research.
