Some patients who have presented a thromboembolic event persist with a high risk of recurrence despite anticoagulant treatment. It has been suggested that adding an inferior vena cava filter may reduce this risk, but the clinical effects of this measure are not clear. To answer this question we searched in Epistemonikos database, which is maintained by screening multiple information sources. We identified three systematic reviews including four randomized trials answering this question. We extracted data, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. We concluded there might be little or no difference on the occurrence of deep venous thrombosis by adding an inferior vena cava filter in anticoagulated patients, and it is not clear whether there are differences in the occurrence of pulmonary embolism or mortality because the certainty of evidence is very low.
BACKGROUND: Deep venous thrombosis (DVT) arises with an incidence of about 1 per 1000 persons per year; 4-10% of all DVTs are located in an upper extremity (DVT-UE). DVT-UE can lead to complications such as post-thrombotic syndrome and pulmonary embolism and carries a high mortality.
METHODS: This review is based on pertinent literature, published from January 1980 to May 2016, that was retrieved by a systematic search, employing the PRISMA criteria, carried out in four databases: PubMed (n = 749), EMBASE (n = 789), SciSearch (n = 0), and the Cochrane Library (n = 12). Guidelines were included in the search.
RESULTS: DVT-UE arises mainly in patients with severe underlying diseases, especially cancer (odds ratio [OR] 18.1; 95% confidence interval [9.4; 35.1]). The insertion of venous catheters-particularly central venous catheters-also elevates the risk of DVT-UE. Its clinical manifestations are nonspecific. Diagnostic algorithms are of little use, but ultrasonography is very helpful in diagnosis. DVT-UE is treated by anticoagulation, with heparin at first and then with oral anticoagulants. Direct oral anticoagulants are now being increasingly used. The thrombus is often not totally eradicated. Anticoagulation is generally continued as maintenance treatment for 3-6 months. Interventional techniques can be used for special indications. Patients with DVT-UE have a high mortality, though they often die of their underlying diseases rather than of the DVT-UE or its complications.
CONCLUSION: DVT of the upper extremity is becoming increasingly common, though still much less common than DVT of the lower extremity. The treatment of choice is anticoagulation, which is given analogously to that given for DVT of the lower extremity.
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.
The preferred dosification for low molecular weight heparins is in two doses for most patients with venous thromboembolic disease. A daily dose would make treatment simpler, less expensive and more comfortable while retaining a similar benefit and safety. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified two systematic reviews including five randomized trials. We combined the evidence using meta-analysis and generated a summary of findings table following the GRADE approach. We concluded it is not clear whether the risk of recurrence differs between the two alternatives because the certainty of the evidence is very low, and that administering low molecular weight heparin in two doses might be associated to little or no difference in the risk of major bleeding and mortality.
Venous thromboembolism (VTE) including deep vein thrombosis (DVT) and pulmonary embolism (PE) is commonly encountered in daily clinical practice. After diagnosis, its management frequently carries significant challenges to the clinical practitioner. Treatment of VTE with the inappropriate modality and/or in the inappropriate setting may lead to serious complications and have life-threatening consequences. As a result of an initiative of the Ministry of Health of the Kingdom 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 Guideline working group, this clinical practice guideline was produced to assist health care providers in VTE management. Two questions were identified and were related to the inpatient versus outpatient treatment of acute DVT, and the early versus standard discharge from hospital for patients with acute PE. The corresponding recommendations were made following the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach.
CONTEXTE: anticoagulation orale correctement dosé empêche efficacement les événements thromboemboliques. Il est difficile de savoir si les patients adultes avec une indication pour anticoagulation orale à long terme peuvent bénéficier de l'auto-gestion en termes de critères d'évaluation axés sur le patient et les valeurs de coagulation améliorées.
Méthode: Nous avons cherché sélectivement la base de données Medline pour des examens systématiques de haute qualité basés sur des essais contrôlés randomisés de l'auto-mesure ou de l'auto-gestion de l'anticoagulation orale, par rapport à un traitement standard.
RÉSULTATS: Nous avons identifié huit articles de revue sur la base de chevauchement des ensembles de ran - essais cliniques domisées. Dans tous ces examens systématiques, les patients qui ont effectué l'auto-mesure ou l'auto-gestion avaient un taux d'événements thromboemboliques 40% à 50%; dans six d'entre eux, la mortalité était aussi significativement plus faible, de 30% à 50%. l'analyse des sous-groupes a révélé que ces effets étaient présents exclusivement chez les patients qui ont effectué l'auto-gestion, et non à ceux qui n'effectués auto-mesure. Aucun des articles d'examen a révélé une différence dans la fréquence des événements hémorragiques graves. Qualité de vie et la satisfaction des patients ont été classés en cinq examens, qui, cependant, utilisés divers instruments, de sorte qu'aucune conclusion claire n'a pu être tirée. Tous les articles de revue documenté une amélioration des valeurs de la coagulation, mais les informations sur la signification statistique a été la plupart du temps manque.
CONCLUSION: Les adultes ayant une indication pour l'administration orale avantage anticoagulation à long terme de l'auto-gestion, par rapport à un traitement standard avec la gestion de l'administration par un médecin. Une limitation de cette étude est que les multiples articles de revue sur lesquels elle se fonde étaient en grande partie des analyses du même groupe d'essais cliniques.
BACKGROUND: Many systematic reviews exist on interventions to improve safe and effective medicines use by consumers, but research is distributed across diseases, populations and settings. The scope and focus of such reviews also vary widely, creating challenges for decision-makers seeking to inform decisions by using the evidence on consumers’ medicines use.
This is an update of a 2011 overview of systematic reviews, which synthesises the evidence, irrespective of disease, medicine type, population or setting, on the effectiveness of interventions to improve consumers' medicines use.
OBJECTIVES: To assess the effects of interventions which target healthcare consumers to promote safe and effective medicines use, by synthesising review-level evidence.
SEARCH METHODS: We included systematic reviews published on the Cochrane Database of Systematic Reviews and the Database of Abstracts of Reviews of Effects. We identified relevant reviews by handsearching databases from their start dates to March 2012.
SELECTION CRITERIA: We screened and ranked reviews based on relevance to consumers’ medicines use, using criteria developed for this overview.
DATA COLLECTION AND ANALYSIS: We used standardised forms to extract data, and assessed reviews for methodological quality using the AMSTAR tool. We used standardised language to summarise results within and across reviews; and gave bottom-line statements about intervention effectiveness. Two review authors screened and selected reviews, and extracted and analysed data. We used a taxonomy of interventions to categorise reviews and guide syntheses.
MAIN RESULTS: We included 75 systematic reviews of varied methodological quality. Reviews assessed interventions with diverse aims including support for behaviour change, risk minimisation and skills acquisition. No reviews aimed to promote systems-level consumer participation in medicines-related activities. Medicines adherence was the most frequently-reported outcome, but others such as knowledge, clinical and service-use outcomes were also reported. Adverse events were less commonly identified, while those associated with the interventions themselves, or costs, were rarely reported.
Looking across reviews, for most outcomes, medicines self-monitoring and self-management programmes appear generally effective to improve medicines use, adherence, adverse events and clinical outcomes; and to reduce mortality in people self-managing antithrombotic therapy. However, some participants were unable to complete these interventions, suggesting they may not be suitable for everyone.
Other promising interventions to improve adherence and other key medicines-use outcomes, which require further investigation to be more certain of their effects, include:
· simplified dosing regimens: with positive effects on adherence;
· interventions involving pharmacists in medicines management, such as medicines reviews (with positive effects on adherence and use, medicines problems and clinical outcomes) and pharmaceutical care services (consultation between pharmacist and patient to resolve medicines problems, develop a care plan and provide follow-up; with positive effects on adherence and knowledge).
Several other strategies showed some positive effects, particularly relating to adherence, and other outcomes, but their effects were less consistent overall and so need further study. These included:
· delayed antibiotic prescriptions: effective to decrease antibiotic use but with mixed effects on clinical outcomes, adverse effects and satisfaction;
· practical strategies like reminders, cues and/or organisers, reminder packaging and material incentives: with positive, although somewhat mixed effects on adherence;
· education delivered with self-management skills training, counselling, support, training or enhanced follow-up; information and counselling delivered together; or education/information as part of pharmacist-delivered packages of care: with positive effects on adherence, medicines use, clinical outcomes and knowledge, but with mixed effects in some studies;
· financial incentives: with positive, but mixed, effects on adherence.
Several strategies also showed promise in promoting immunisation uptake, but require further study to be more certain of their effects. These included organisational interventions; reminders and recall; financial incentives; home visits; free vaccination; lay health worker interventions; and facilitators working with physicians to promote immunisation uptake. Education and/or information strategies also showed some positive but even less consistent effects on immunisation uptake, and need further assessment of effectiveness and investigation of heterogeneity.
There are many different potential pathways through which consumers' use of medicines could be targeted to improve outcomes, and simple interventions may be as effective as complex strategies. However, no single intervention assessed was effective to improve all medicines-use outcomes across all diseases, medicines, populations or settings.
Even where interventions showed promise, the assembled evidence often only provided part of the picture: for example, simplified dosing regimens seem effective for improving adherence, but there is not yet sufficient information to identify an optimal regimen.
In some instances interventions appear ineffective: for example, the evidence suggests that directly observed therapy may be generally ineffective for improving treatment completion, adherence or clinical outcomes.
In other cases, interventions may have variable effects across outcomes. As an example, strategies providing information or education as single interventions appear ineffective to improve medicines adherence or clinical outcomes, but may be effective to improve knowledge; an important outcome for promoting consumers' informed medicines choices.
Despite a doubling in the number of reviews included in this updated overview, uncertainty still exists about the effectiveness of many interventions, and the evidence on what works remains sparse for several populations, including children and young people, carers, and people with multimorbidity.
AUTHORS' CONCLUSIONS: This overview presents evidence from 75 reviews that have synthesised trials and other studies evaluating the effects of interventions to improve consumers' medicines use.
Systematically assembling the evidence across reviews allows identification of effective or promising interventions to improve consumers’ medicines use, as well as those for which the evidence indicates ineffectiveness or uncertainty.
Decision makers faced with implementing interventions to improve consumers' medicines use can use this overview to inform decisions about which interventions may be most promising to improve particular outcomes. The intervention taxonomy may also assist people to consider the strategies available in relation to specific purposes, for example, gaining skills or being involved in decision making. Researchers and funders can use this overview to identify where more research is needed and assess its priority. The limitations of the available literature due to the lack of evidence for important outcomes and important populations, such as people with multimorbidity, should also be considered in practice and policy decisions.
A best evidence topic was written according to a structured protocol, to answer the question: 'In patients taking warfarin, is home self-monitoring of international normalized ratio (INR) safer than clinic-based testing in reducing bleeding, thrombotic events and death?' Altogether, 268 papers were found using the reported search. Five papers represented the highest level of evidence to answer the clinical question (four systematic reviews with meta-analysis and one meta-analysis). The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. The principal outcomes of interest were death, major haemorrhage, major thromboembolism, and time (or percentage time) spent within the therapeutic range, compared between self-monitoring/self-management and conventional management. Self-monitoring/self-management was associated with a significantly reduced risk of all-cause mortality of 26-42%. All meta-analyses reported on major thromboembolism, finding significant reductions in risk of ~50%. One meta-analysis found a 35% reduction in the risk of major haemorrhage, with the other four studies finding no significant difference. Only one study found self-monitoring/self-management to be associated with a significantly greater proportion of time within range, with another finding no significant difference in either the percentage of therapeutic results or in the time within range. The remaining two could not combine data for meta-analysis owing to methodological heterogeneity. We conclude that self-monitoring/self-management appears to be safer than conventional management. It is associated with consistently lower rates of thromboembolism and may also be associated with reduced risk of bleeding and death. This supports the updated guidance from the American College of Chest Physicians, recommending self-management of INR for patients who are both competent and motivated.
This article describes the pharmacology of approved parenteral anticoagulants. These include the indirect anticoagulants, unfractionated heparin (UFH), low-molecular-weight heparins (LMWHs), fondaparinux, and danaparoid, as well as the direct thrombin inhibitors hirudin, bivalirudin, and argatroban. UFH is a heterogeneous mixture of glycosaminoglycans that bind to antithrombin via a unique pentasaccharide sequence and catalyze the inactivation of thrombin, factor Xa, and other clotting enzymes. Heparin also binds to cells and plasma proteins other than antithrombin causing unpredictable pharmacokinetic and pharmacodynamic properties and triggering nonhemorrhagic side effects, such as heparin-induced thrombocytopenia (HIT) and osteoporosis. LMWHs have greater inhibitory activity against factor Xa than thrombin and exhibit less binding to cells and plasma proteins than heparin. Consequently, LMWH preparations have more predictable pharmacokinetic and pharmacodynamic properties, have a longer half-life than heparin, and are associated with a lower risk of nonhemorrhagic side effects. LMWHs can be administered once daily or bid by subcutaneous injection, without coagulation monitoring. Based on their greater convenience, LMWHs have replaced UFH for many clinical indications. Fondaparinux, a synthetic pentasaccharide, catalyzes the inhibition of factor Xa, but not thrombin, in an antithrombin-dependent fashion. Fondaparinux binds only to antithrombin. Therefore, fondaparinux-associated HIT or osteoporosis is unlikely to occur. Fondaparinux exhibits complete bioavailability when administered subcutaneously, has a longer half-life than LMWHs, and is given once daily by subcutaneous injection in fixed doses, without coagulation monitoring. Three additional parenteral direct thrombin inhibitors and danaparoid are approved as alternatives to heparin in patients with HIT.
Some patients who have presented a thromboembolic event persist with a high risk of recurrence despite anticoagulant treatment. It has been suggested that adding an inferior vena cava filter may reduce this risk, but the clinical effects of this measure are not clear. To answer this question we searched in Epistemonikos database, which is maintained by screening multiple information sources. We identified three systematic reviews including four randomized trials answering this question. We extracted data, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. We concluded there might be little or no difference on the occurrence of deep venous thrombosis by adding an inferior vena cava filter in anticoagulated patients, and it is not clear whether there are differences in the occurrence of pulmonary embolism or mortality because the certainty of evidence is very low.
