BACKGROUND AND OBJECTIVES: Atrial fibrillation (AF) and the associated risk of stroke are emerging epidemics throughout the world. Suboptimal use of oral anticoagulants for stroke prevention has been widely reported from observational studies. In recent years, direct oral anticoagulants (DOACs) have been introduced for thromboprophylaxis. We conducted a systematic literature review to evaluate current practices of anticoagulation in AF, pharmacologic features and adoption patterns of DOACs, their impacts on proportion of eligible patients with AF who receive oral anticoagulants, persisting challenges and future prospects for optimal anticoagulation.
LITERATURE SOURCE AND SELECTION CRITERIA: In conducting this review, we considered the results of relevant prospective and retrospective observational studies from real-world practice settings. PubMed (MEDLINE), Scopus (RIS), Google Scholar, EMBASE and Web of Science were used to source relevant literature. There were no date limitations, while language was limited to English. Selection was limited to articles from peer reviewed journals and related to our topic.
RESULTS: Most studies identified in this review indicated suboptimal use of anticoagulants is a persisting challenge despite the availability of DOACs. Underuse of oral anticoagulants is apparent particularly in patients with a high risk of stroke. DOAC adoption trends are quite variable, with slow integration into clinical practice reported in most countries; there has been limited impact to date on prescribing practice.
CONCLUSION: Available data from clinical practice suggest that suboptimal oral anticoagulant use in patients with AF and poor compliance with guidelines still remain commonplace despite transition to a new era of anticoagulation featuring DOACs.
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.
BACKGROUND AND OBJECTIVES: Venous thromboembolism (VTE) is commonly encountered in the daily clinical practice. Cancer is an important VTE risk factor. Proper thromboprophylaxis is key to prevent VTE in patients with cancer, and proper treatment is essential to reduce VTE complications and adverse events associated with the therapy.
DESIGN AND SETTINGS: As a result of an initiative of the Ministry of Health of Saudi Arabia, an expert panel led by the Saudi Association for Venous Thrombo-Embolism (a subsidiary of the Saudi Thoracic Society) and the Saudi Scientific Hematology Society with the methodological support of the McMaster University working group produced this clinical practice guideline to assist health care providers in evidence-based clinical decision-making for VTE prophylaxis and treatment in patients with cancer.
METHODS: Six questions related to thromboprophylaxis and antithrombotic therapy were identified and the corresponding recommendations were made following the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach.
RESULTS: Question 1. Should heparin versus no heparin be used in outpatients with cancer who have no other therapeutic or prophylactic indication for anticoagulation?
RECOMMENDATION: For outpatients with cancer, the Saudi Expert Panel suggests against routine thromboprophylaxis with heparin (weak recommendation; moderate quality evidence).Question 2. Should oral anticoagulation versus no oral anticoagulation be used in outpatients with cancer who have no other therapeutic or prophylactic indication for anticoagulation?
RECOMMENDATION: For outpatients with cancer, the Saudi Expert Panel recommends against thromboprophylaxis with oral anticoagulation (strong recommendation; moderate quality evidence).Question 3. Should parenteral anticoagulation versus no anticoagulation be used in patients with cancer and central venous catheters?
RECOMMENDATION: For outpatients with cancer and central venous catheters, the Saudi Expert Panel suggests thromboprophylaxis with parenteral anticoagulation (weak recommendation; moderate quality evidence).Question 4. Should oral anticoagulation versus no anticoagulation be used in patients with cancer and central venous catheters?
RECOMMENDATION: For outpatients with cancer and central venous catheters, the Saudi Expert Panel suggests against thromboprophylaxis with oral anticoagulation (weak recommendation; low quality evidence).Question 5. Should low-molecular-weight heparin versus unfractionated heparin be used in patients with cancer being initiated on treatment for venous thromboembolism?
RECOMMENDATION: In patients with cancer being initiated on treatment for venous thromboembolism, the Saudi Expert Panel suggests low-molecular-weight heparin over intravenous unfractionated heparin (weak; very low quality evidence).Question 6. Should heparin versus oral anticoagulation be used in patients with cancer requiring long-term treatment of VTE?
RECOMMENDATION: In patients with metastatic cancer requiring long-term treatment of VTE, the Saudi Expert Panel recommends low-molecular-weight heparin (LMWH) over vitamin K antagonists (VKAs) (strong recommendation; moderate quality evidence). In patients with non-metastatic cancer requiring long-term treatment of venous thromboembolism, the Saudi Expert Panel suggests LMWH over VKA (weak recommendation; moderate quality evidence).
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.
INTRODUCTION: avantages et les inconvénients relatifs des anticoagulants sont nécessaires pour les décisions concernant l'anticoagulation appropriée chez les patients atteints de cancer.
OBJECTIFS: Examiner les avantages et les inconvénients des anticoagulants pour des indications d'amélioration prophylactiques, thérapeutiques et de survie chez les patients atteints de cancer.
Patients et méthodes: Vue d'ensemble de 6 recensions systématiques de l'anticoagulation dans le cancer de la suite de la Cochrane Collaboration et classement des recommandations d'évaluation, de développement et d'évaluation méthodologie.
RÉSULTATS: Central veineuse cathéters thromboprophylaxie avec de l'héparine ou la warfarine ne réduit pas significativement l'incidence de la thrombose veineuse profonde symptomatique (TVP) (risque relatif [RR] 0,43, IC 95% 0,18 à 1,06 et RR = 0,62, IC 95% de 0,30 à 1,27 respectivement) . Pour la thromboprophylaxie périopératoire, à faible poids moléculaire héparine (HBPM) et l'héparine non fractionnée (HNF) ont des effets similaires sur la mortalité (RR 0,89, IC 95% 0,61 à 1,28) et la morbidité. Pour le traitement initial de la maladie thromboembolique veineuse (MTEV), les HBPM par rapport à l'héparine non fractionnée réduit la mortalité à 3 mois (RR 0,71, IC 95% de 0,52 à 0,98). Pour le traitement à long terme de la TEV, les HBPM par rapport à des antagonistes de la vitamine K réduit la récurrence de TEV (hazard ratio [HR] 0,47, IC 95% de 0,32 à 0,71), mais pas la mortalité (HR 0,96, IC 95% 0,81 à 1,14). Comme les interventions visant à améliorer la survie, la warfarine suggère un bénéfice de survie à 6 mois dans le sous-groupe de cancer du poumon à petites cellules (SCLC) (RR = 0,69, IC 95% de 0,50 à 0,96), tandis que l'héparine suggèrent un bénéfice de survie chez les patients atteints de cancer en général (RH 0,77, IC 95% 0,65 à 0,91) et chez ceux ayant limité CPPC en particulier (HR 0,56, IC 95% 0,38 au 0,83).
CONCLUSIONS: Chez les patients atteints de cancer, les données actuelles ne supporte pas l'utilisation systématique de la thromboprophylaxie pour les cathéters veineux centraux ou un anticoagulant spécifique pour la thromboprophylaxie postopératoire. Anticoagulants peut améliorer la survie, mais davantage de données seront utiles dans le choix des sous-groupes qui bénéficient le plus.
Atrial fibrillation (AF) and the associated risk of stroke are emerging epidemics throughout the world. Suboptimal use of oral anticoagulants for stroke prevention has been widely reported from observational studies. In recent years, direct oral anticoagulants (DOACs) have been introduced for thromboprophylaxis. We conducted a systematic literature review to evaluate current practices of anticoagulation in AF, pharmacologic features and adoption patterns of DOACs, their impacts on proportion of eligible patients with AF who receive oral anticoagulants, persisting challenges and future prospects for optimal anticoagulation.
LITERATURE SOURCE AND SELECTION CRITERIA:
In conducting this review, we considered the results of relevant prospective and retrospective observational studies from real-world practice settings. PubMed (MEDLINE), Scopus (RIS), Google Scholar, EMBASE and Web of Science were used to source relevant literature. There were no date limitations, while language was limited to English. Selection was limited to articles from peer reviewed journals and related to our topic.
RESULTS:
Most studies identified in this review indicated suboptimal use of anticoagulants is a persisting challenge despite the availability of DOACs. Underuse of oral anticoagulants is apparent particularly in patients with a high risk of stroke. DOAC adoption trends are quite variable, with slow integration into clinical practice reported in most countries; there has been limited impact to date on prescribing practice.
CONCLUSION:
Available data from clinical practice suggest that suboptimal oral anticoagulant use in patients with AF and poor compliance with guidelines still remain commonplace despite transition to a new era of anticoagulation featuring DOACs.
