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: 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.
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.
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).
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.
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.
BACKGROUND: This guideline focuses on long-term administration of antithrombotic drugs designed for primary and secondary prevention of cardiovascular disease, including two new antiplatelet therapies.
METHODS: The methods of this guideline follow those described in Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines in this supplement.
RESULTS: We present 23 recommendations for pertinent clinical questions. For primary prevention of cardiovascular disease, we suggest low-dose aspirin (75-100 mg/d) in patients aged > 50 years over no aspirin therapy (Grade 2B). For patients with established coronary artery disease, defined as patients 1-year post-acute coronary syndrome, with prior revascularization, coronary stenoses > 50% by coronary angiogram, and/or evidence for cardiac ischemia on diagnostic testing, we recommend long-term low-dose aspirin or clopidogrel (75 mg/d) (Grade 1A). For patients with acute coronary syndromes who undergo percutaneous coronary intervention (PCI) with stent placement, we recommend for the first year dual antiplatelet therapy with low-dose aspirin in combination with ticagrelor 90 mg bid, clopidogrel 75 mg/d, or prasugrel 10 mg/d over single antiplatelet therapy (Grade 1B). For patients undergoing elective PCI with stent placement, we recommend aspirin (75-325 mg/d) and clopidogrel for a minimum duration of 1 month (bare-metal stents) or 3 to 6 months (drug-eluting stents) (Grade 1A). We suggest continuing low-dose aspirin plus clopidogrel for 12 months for all stents (Grade 2C). Thereafter, we recommend single antiplatelet therapy over continuation of dual antiplatelet therapy (Grade 1B).
CONCLUSIONS: Recommendations continue to favor single antiplatelet therapy for patients with established coronary artery disease. For patients with acute coronary syndromes or undergoing elective PCI with stent placement, dual antiplatelet therapy for up to 1 year is warranted.
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.
