Our choice of terminology reflects the distinct clinical intentions of the different phases of VTE management, linking them to important clinical decisions addressed in the guidelines, rather than using terms reflecting the relative duration of therapy. Patients placed a high value on the benefits of risk reduction in VTE recurrence and PTS.311 However, the panel considered the existence of an important variability in how individual patients may value the risk of recurrent VTE vs the risk of bleeding. Among these recommendations, the guideline panel strongly recommended
Major transient risk factors (occur within 3 mo of VTE diagnosis); examples include: Surgery with general anesthesia for ≥30 min, Confined to bed in hospital for ≥3 d with an acute illness (“bathroom privileges” only). A controlled clinical study in patients with aortic ball valves, Thromboembolic risk in prosthetic valve carriers. Follow-up of a randomized study, A comparative randomized trial of heparin versus streptokinase in the treatment of acute proximal venous thrombosis: an interim report of a prospective trial, Early results of thrombolysis vs anticoagulation in iliofemoral venous thrombosis. Although the evidence supporting a reduced risk for bleeding with the use of a DOAC compared with a VKA was of high certainty, the lack of benefit for the VTE outcomes resulted in the conditional recommendation. Remarks: Patients who present with a new VTE event during therapeutic VKA treatment should be further investigated to identify potential underlying causes. October 8, 2020. Therefore, it was not possible to completely rule out a small difference between the alternatives on such outcomes. For patients with proximal DVT and significant preexisting cardiopulmonary disease, as well as for patients with PE and hemodynamic compromise, the ASH guideline panel suggests anticoagulation alone rather than anticoagulation plus insertion of an inferior vena cava (IVC) filter (conditional recommendations based on low certainty in the evidence of effects ⨁⨁○○). Published On. A meta-analysis of the interventional trials. Available at: Clinical and safety outcomes associated with treatment of acute venous thromboembolism: a systematic review and meta-analysis, Comparison of the novel oral anticoagulants apixaban, dabigatran, edoxaban, and rivaroxaban in the initial and long-term treatment and prevention of venous thromboembolism: systematic review and network meta-analysis, Non-vitamin K oral anticoagulants in patients with pulmonary embolism: a systematic review and meta-analysis of the literature, Direct oral anticoagulants for the treatment of unprovoked venous thromboembolism: a meta-analysis of randomised controlled trials, Efficacy and safety of novel oral anticoagulants for treatment of acute venous thromboembolism: direct and adjusted indirect meta-analysis of randomised controlled trials, Comparison of dabigatran vs. warfarin in acute venous thromboemboly: systematic review, Direct oral anticoagulants in the treatment of venous thromboembolism, with a focus on patients with pulmonary embolism: an evidence-based review, Direct oral anticoagulants in the treatment of acute venous thromboembolism: a systematic review and meta-analysis, New oral anticoagulants in the treatment of acute venous thromboembolism - a systematic review with indirect comparisons [published correction appears in Vasa. We considered that the avoidance of PE, DVT, and major bleeding was critical for patients. Approximately 3% to 5% of patients with an acute PE present with hemodynamic compromise, defined as a systolic blood pressure <90 mm Hg or a decrease in systolic blood pressure ≥40 mm Hg from baseline.205,206 These patients are at a significantly greater risk for mortality, as high as 50% by 90 days,205 compared with patients with acute PE who do not present with hemodynamic compromise. We did not find any economic evaluation assessing the cost utility of a DOAC vs LMWH for patients with DVT and/or PE during treatment with VKA. The American Society of Hematology (ASH) has developed new guidelines for managing venous thromboembolism (VTE). Other variables that may be important for the individual patient include whether the medication must be taken with food, preference for once-daily vs twice-daily dosing, the need to use a pill box, or the need to crush tablets prior to administration. Finally, patients with antiphospholipid antibody syndrome, bariatric surgery, short gut, or other conditions that may influence medication absorption, as well as patients at extremes of body weight, are not optimal candidates for DOACs. There were significant subgroup effects of different antithrombotic interventions on DVT outcome. The PESI1 and simplified PESI2 have been most widely validated. Phase 1 results: a cooperative study, Tissue plasminogen activator for the treatment of acute pulmonary embolism. The certainties of the evidence were judged moderate because of imprecision. We identified 1 RCT316 to inform this recommendation. For patients with a recurrent unprovoked DVT and/or PE, the ASH guideline panel recommends indefinite antithrombotic therapy over stopping anticoagulation after completion of primary treatment (strong recommendation based on moderate certainty in the evidence of effects ⨁⨁⨁○). Additionally, panel members were asked to suggest any studies that may have been missed and fulfilled the inclusion criteria for the individual questions. For selected patients with a chronic risk factor for which some improvement is expected over time (eg, improved mobility with rehabilitation), a longer course of anticoagulation for the primary treatment phase (eg, 6-12 months) could be justified. Prevention trial, Bleeding during warfarin and aspirin therapy in patients with atrial fibrillation: the AFASAK 2 study. In the trial evaluating residual vein thrombosis by ultrasonography, participants in the intervention group received anticoagulation for an average of 4 to 5 months longer than did controls. However, the more relevant trade-off for patients may be between the risk of PTS and the risk of major bleeding. The mean follow-up time was 351 days. The same was true for the outcomes PE and DVT, but in addition to indirectness and imprecision, the panel also rated these outcomes down by risk of bias, given that none of the included trials was blinded. We acknowledge that not all of them are covered in this guideline. Four Markov model analyses of cost-effectiveness for extended antithrombotic therapy vs limited antithrombotic therapy for VTE treatment were identified. Most patients with DVT and/or PE provoked by temporary risk factors will discontinue anticoagulant therapy after completion of the primary treatment. The panel rated the following outcomes as critical for clinical decision making across questions: mortality, PE, proximal DVT, and major bleeding. It also covers testing for conditions that can make a DVT … This recommendation applies to the patient who sustains a VTE related to a transient risk factor, who also has a history of VTE that was unprovoked or provoked by a chronic risk factor (Recommendation 24a) or who has a history of VTE that was provoked by a transient risk factor (Recommendation 24b). This guideline covers diagnosing and managing venous thromboembolic diseases in adults. Internal medicine physicians are specialists who apply scientific knowledge and clinical expertise to the diagnosis, treatment, and compassionate care of adults across the spectrum from health to complex illness. In a low-risk population,268 a longer course of anticoagulation also reduced the risk of DVT (ARR, 18 fewer per 1000 patients; 95% CI, 21 fewer to 14 fewer). The EtD frameworks are shown online at: https://guidelines.gradepro.org/profile/86ED15E4-C608-F07D-9AA7-5F3B5AE994B0 and https://guidelines.gradepro.org/profile/15281C02-EE9F-4E90-B895-5A8EEA854AB9. When using a DOAC for a longer course of anticoagulation, the risk of DVT was reduced in the study population (RR, 0.21; 95% CI, 0.11-0.41; ARR, 62 fewer per 1000 patients; 95% CI, 70 fewer to 46 fewer; high-certainty evidence), as well as in a low-risk population268 (ARR, 32 fewer per 1000 patients; 95% CI, 36 fewer to 24 fewer; moderate-certainty evidence). For patients with a contraindication to anticoagulation, insertion of a retrievable IVC filter may be indicated, with retrieval as soon as the patient is able to receive anticoagulation. However, we did observe a reduction in the risk of DVT (RR, 0.80; 95% CI, 0.59-1.09; ARR, 5 fewer per 1000 patients; 95% CI, 11 fewer to 2 more; moderate-certainty evidence), although this was not statistically significant. For patients with PE, systemic
Analysis of RCTs showed that treating patients with PE and a low risk for complications at home, rather than in the hospital, may reduce the risk of mortality at 30 days (RR, 0.33; 95% CI, 0.01-7.98; ARR, 2 fewer per 1000 patients, 95% CI, 2 fewer to 16 more for low-risk PE patients treated in the hospital51 ; low-certainty evidence) and 90 days (RR, 0.98; 95% CI, 0.06-15.58; ARR, 0 fewer per 1000 patients, 95% CI, 7 fewer to 108 more for low-risk PE patients treated in the hospital51 ; low-certainty evidence), although CIs included significant benefit and harm. In March 2020, most anticoagulants were off label for the treatment of DVT or PE in people with active cancer. When a VKA or LMWH was used for indefinite anticoagulation, we observed a reduction in the risk of DVT in the study population (RR, 0.17; 95% CI, 0.05-0.53; ARR, 54 fewer per 1000 patients; 95% CI, 61 fewer to 30 fewer), as well as for patients with recurrent unprovoked VTE (ARR, 55 fewer per 1000 patients; 95% CI, 63 fewer to 31 fewer; high-certainty evidence).269,324 Aspirin also reduced the risk of recurrent DVT in the study population (RR, 0.55; 95% CI, 0.31-0.98; ARR, 64 fewer per 1000 patients; 95% CI, 98 fewer to 3 fewer), as well as for patients with recurrent unprovoked VTE (ARR, 30 fewer per 1000 patients; 95% CI, 46 fewer to 1 fewer; moderate-certainty evidence).269,324 Our analysis showed a potential decrease in mortality when using indefinite antithrombotic therapy compared with a defined duration of anticoagulation, without statistical significance (RR, 0.75; 95% CI, 0.49-1.13; ARR, 5 fewer per 1000 patients; 95% CI, 9 fewer to 2 more; moderate-certainty evidence). It also covers testing for conditions that can make a DVT or PE more likely, such as thrombophilia (a blood clotting disorder) and cancer. Future research studies need to be conducted in the appropriate patient populations and designed to answer these questions surrounding optimal administration of thrombolytic therapy for patients with PE. The use of indefinite antithrombotic therapy increased the risk of major bleeding (RR, 2.17; 95% CI, 1.40-3.35; ARR, 6 more per 1000 patients; 95% CI, 2 more to 12 more; high-certainty evidence). For patients with PE in whom thrombolysis is considered appropriate, the ASH guideline panel suggests using systemic thrombolysis over catheter-directed thrombolysis (conditional recommendation based on very low certainty in the evidence of effects ⨁○○○). Panelists then selected outcomes of interest for each question a priori, following an approach described in detail elsewhere.28 In brief, the panel first brainstormed all possible outcomes before rating the relative importance for decision making of each. The use of a DOAC instead of a VKA for patients with VTE does not impact mortality (RR, 0.99; 95% CI, 0.85-0.15; ARR, 0 fewer per 1000 patients; 95% CI, 6 fewer to 6 more; moderate-certainty evidence) or the risk of PE (RR, 0.97; 95% CI, 0.77-1.23; ARR, 1 fewer per 1000 patients; 95% CI, 5 fewer to 5 more; moderate-certainty evidence). The Thrombosis Canada clinical guides have been developed to assist clinicians with point of care decision making. For example, patients who require medications that are inhibitors or inducers of P-glycoprotein, or strong inhibitors or inducers of cytochrome P450 3A4 (CYP3A4) enzymes, should consider treatment with a VKA or LMWH rather than a DOAC, given the interactions of these medications with DOACs. The panel considered a negligible cost and savings between the interventions. The use of thrombolysis should be rare for patients with DVT limited to veins below the common femoral vein. There were significant subgroup effects associated with the different antithrombotic interventions on DVT outcome. In populations with a low bleeding risk,37 treating at home instead of treating in the hospital may lead to a reduction of 5 fewer bleeding events per 1000 patients (95% CI, 11 fewer to 6 more; low-certainty evidence). The guideline panel reviewed draft EtD tables before, during, or after the guideline panel meeting and made suggestions for correction and identified missing evidence. Other researchers participated to fulfill requirements of an academic degree or program. Indefinite antithrombotic therapy also showed a reduced risk for DVT in the study population (RR, 0.20; 95% CI, 0.12-0.34; ARR, 50 fewer per 1000 patients; 95% CI, 56 fewer to 42 fewer; high-certainty evidence), as well as for patients with chronic risk factors at 1 year269,274 (ARR, 45 fewer per 1000 patients; 95% CI, 48 fewer to 41 fewer). However, 4 panel members believed the recommendation should have been graded as strong based on the lack of evidence showing meaningful clinical benefits outweighing the known bleeding risks associated with systemic thrombolysis. Patients with unprovoked VTE, defined as occurring in the absence of any identifiable transient or chronic acquired risk factors, have the highest risk for recurrent VTE if anticoagulation is discontinued after the primary treatment phase. The sample size in the SOX trial353 (n = 806) was larger than in the rest of the trials, and patients with proximal DVT were randomized to elastic stockings with an ankle pressure of 30 to 40 mm Hg or to placebo stockings with an ankle pressure ≤5 mm Hg for 2 years. Our analysis showed a potential increase in mortality when using a longer course of anticoagulation than with a shorter course of anticoagulation, without statistical significance (RR, 1.38; 95% CI, 0.85-2.23; ARR, 7 more per 1000 patients; 95% CI, 3 fewer to 22 more; moderate-certainty evidence). is suggested. Finally, we considered that thrombolysis is acceptable and feasible to implement in most scenarios. DVT has an annual incidence of about 1–2 per 1000 people. Implementation of this recommendation depends on the ability to rapidly evaluate patients, confirm the diagnosis of PE and associated hemodynamic compromise, and initiate appropriate therapy. We considered that most informed patients would place more value in avoiding death than in the risk of bleeding associated with the intervention. Participants were randomized to insertion of a nonretrievable IVC filter in addition to anticoagulation or to anticoagulation alone. Deep vein thrombosis (DVT) is the formation of a thrombus (blood clot) in a deep vein, usually in the legs, which partially or completely obstructs blood flow. Decision aids may be useful in helping individuals to make decisions consistent with their individual risks, values, and preferences. Among the recommendations are the following: The guidelines also address longer-term anticoagulation, divided into the periods
The panel considered that aspirin discontinuation was probably feasible but that acceptability varies. The certainty in the evidence from observational studies was judged very low for long-term mortality for the same reasons as well as a high degree of inconsistency among the pooled estimates. Based on the low certainty in the evidence, the ASH guideline panel has suggested against the addition of thrombolytic therapy to anticoagulation for patients with proximal DVT. Part D describes new interests disclosed by individuals after appointment. Clinical study of venous filter implantation combined with catheterization thrombolytic therapy for deep vein thrombosis [in Chinese]. The outcomes were measured in both groups immediately at the end of the extended-duration treatment. Clinicians must make decisions on the basis of the clinical presentation of each individual patient, ideally through a shared decision-making process that considers the patient’s values and preferences with respect to the anticipated outcomes of the chosen option. Trial NL2562 (NTR2680). Supplement 3 provides the complete “Disclosure of Interests” forms of researchers who contributed to these guidelines. Acquired (environmental) risk factors for DVT and/or PE that are considered chronic include cancer (discussed in a future guideline document from ASH), certain autoimmune disorders (eg, inflammatory bowel disease or antiphospholipid syndrome), and chronic immobility (Table 3).237 Some of these risk factors may fluctuate over time (eg, the autoimmune disorders), but many of these patients are considered to be at a higher risk for recurrent thromboembolism if anticoagulant therapy is discontinued. The panel agreed on recommendations (including direction and strength), remarks, and qualifications by consensus or, in rare instances, by voting (an 80% majority was required for a strong recommendation) based on the balance of all desirable and undesirable consequences. Hospital stay is associated with procedures, risk, and burden for patients. However, some patients may experience discomfort, skin breakdown, allergic reaction, or significant cost to acquire the stockings. Magnetic resonance venography to assess thrombus resolution with edoxaban monotherapy versus parenteral anticoagulation/warfarin for symptomatic deep vein thrombosis: a multicenter feasibility study. Remarks: Lower-dose DOAC regimens that may be considered for patients who have completed primary treatment and will continue with a DOAC include rivaroxaban, 10 mg daily, or apixaban, 2.5 mg twice daily. 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