The following are the Summary of Recommendations from Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report [PubMed Abstract] [Full Text HTML] [Full Text PDF] Chest. 2016 Feb;149(2):315-52. doi: 10.1016/j.chest.2015.11.026. Epub 2016 Jan 7:
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. CHEST 2016; 149(2):315-352
Note on Shaded Text: In this guideline, shaded text with an asterisk (shading appears in PDF only) indicates recommendations that are newly added or have been changed since the publication of Antithrombotic Therapy for VTE Disease: Antithrombotic Therapy and Prevention of Thrombosis (9th edition): American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Recommendations that remain unchanged since that edition are not shaded. The order of our presentation of the non-vitamin K oral anticoagulants (dabigatran, rivaroxaban, apixaban, edoxaban) is based on the chronology of publication of the phase 3 trials in VTE treatment and should not be interpreted as the guideline panel’s order of preference for the use of these agents.
Summary of Recommendations
Choice of Long-Term (First 3 Months) and Extended (No Scheduled Stop Date) Anticoagulant
1. In patients with proximal DVT or pulmonary embolism (PE), we recommend long-term (3 months) anticoagulant therapy over no such therapy (Grade 1B).
*2. In patients with DVT of the leg or PE and no cancer, as long-term (first 3 months) anticoagulant therapy, we suggest dabigatran, rivaroxaban, apixaban, or edoxaban over vitamin K antagonist (VKA) therapy (all Grade 2B). For patients with DVT of the leg or PE and no cancer who are not treated with dabigatran, rivaroxaban, apixaban, or edoxaban, we suggest VKA therapy over low-molecular weight heparin (LMWH) (Grade 2C). Remarks: Initial parenteral anticoagulation is given before dabigatran and edoxaban, is not given before rivaroxaban and apixaban, and is overlapped with VKA therapy. See text for factors that influence choice of therapy.
*3. In patients with DVT of the leg or PE and cancer
(“cancer-associated thrombosis”), as long-term (first
3 months) anticoagulant therapy, we suggest LMWH
over VKA therapy (Grade 2C), dabigatran (Grade
2C), rivaroxaban (Grade 2C), apixaban (Grade 2C),
or edoxaban (Grade 2C).
Remarks: Initial parenteral anticoagulation is given
before dabigatran and edoxaban, is not given before
rivaroxaban and apixaban, and is overlapped with VKA
therapy. See text for factors that influence choice of
therapy.*4. In patients with DVT of the leg or PE who receive
extended therapy, we suggest that there is no need
to change the choice of anticoagulant after the first
3 months (Grade 2C).
Remarks: It may be appropriate for the choice of
anticoagulant to change in response to changes in the
patient’s circumstances or preferences during long-term
or extended phases of treatment.Duration of Anticoagulant Therapy
5. In patients with a proximal DVT of the leg or PE provoked by surgery, we recommend treatment with anticoagulation for 3 months over (i) treatment of a shorter period (Grade 1B), (ii) treatment of a longer time-limited period (eg, 6, 12, or 24 months) (Grade 1B), or (iii) extended therapy (no scheduled stop date) (Grade 1B).
6. In patients with a proximal DVT of the leg or PE provoked by a nonsurgical transient risk factor, we recommend treatment with anticoagulation for 3 months over (i) treatment of a shorter period (Grade 1B) and (ii) treatment of a longer time-limited period (eg, 6, 12, or 24 months) (Grade 1B). We suggest treatment with anticoagulation for 3 months over extended therapy if there is a low or moderate bleeding risk (Grade 2B), and recommend treatment for 3 months over extended therapy if there is a high risk of bleeding (Grade 1B). Remarks: In all patients who receive extended anticoagulant therapy, the continuing use of treatment should be reassessed at periodic intervals (eg, annually).
7. In patients with an isolated distal DVT of the leg provoked by surgery or by a nonsurgical transient risk factor, we suggest treatment with anticoagulation for 3 months over treatment of a shorter period (Grade 2C), we recommend treatment with anticoagulation for 3 months over treatment of a longer time-limited period (eg, 6, 12, or 24 months) (Grade 1B), and we recommend treatment with anticoagulation for 3 months over extended therapy (no scheduled stop date) (Grade 1B). Remarks: Duration of treatment of patients with isolated distal DVT refers to patients in whom a decision has been made to treat with anticoagulant therapy; however, it is anticipated that not all patients who are diagnosed with isolated distal DVT will be prescribed anticoagulants.
8. In patients with an unprovoked DVT of the leg (isolated distal or proximal) or PE, we recommend treatment with anticoagulation for at least 3 months over treatment of a shorter duration (Grade 1B), and we recommend treatment with anticoagulation for 3 months over treatment of a longer time-limited period (eg, 6, 12, or 24 months) (Grade 1B). Remarks: After 3 months of treatment, patients with unprovoked DVT of the leg or PE should be evaluated for the risk-benefit ratio of extended therapy. Duration of treatment of patients with isolated distal DVT refers to patients in whom a decision has been made to treat with anticoagulant therapy; however, it is anticipated that not all patients who are diagnosed with isolated distal DVT will be prescribed anticoagulants.
9. In patients with a first VTE that is an unprovoked proximal DVT of the leg or PE and who have a (i) low or moderate bleeding risk (see text), we suggest extended anticoagulant therapy (no scheduled stop date) over 3 months of therapy (Grade 2B), and (ii) high bleeding risk (see text), we recommend 3 months of anticoagulant therapy over extended therapy (no scheduled stop date) (Grade 1B). Remarks: Patient sex and D-dimer level measured a month after stopping anticoagulant therapy may influence the decision to stop or extend anticoagulant therapy (see text). In all patients who receive extended anticoagulant therapy, the continuing use of treatment should be reassessed at periodic intervals (eg, annually).
10. In patients with a second unprovoked VTE and who have a (i) low bleeding risk (see text), we recommend extended anticoagulant therapy (no scheduled stop date) over 3 months (Grade 1B); (ii) moderate bleeding risk (see text), we suggest extended anticoagulant therapy over 3 months of therapy (Grade 2B); or (iii) high bleeding risk (see text), we suggest 3 months of anticoagulant therapy over extended therapy (no scheduled stop date) (Grade 2B). Remarks: In all patients who receive extended anticoagulant therapy, the continuing use of treatment should be reassessed at periodic intervals (eg, annually). 11. In patients with DVT of the leg or PE and active cancer (“cancer-associated thrombosis”) and who (i) do not have a high bleeding risk, we recommend extended anticoagulant therapy (no scheduled stop date) over 3 months of therapy (Grade 1B), or (ii) have a high bleeding risk, we suggest extended anticoagulant therapy (no scheduled stop date) over 3 months of therapy (Grade 2B). Remarks: In all patients who receive extended anticoagulant therapy, the continuing use of treatment should be reassessed at periodic intervals (eg, annually).
Aspirin for Extended Treatment of VTE
*12. In patients with an unprovoked proximal DVT or PE who are stopping anticoagulant therapy and do not have a contraindication to aspirin, we suggest aspirin over no aspirin to prevent recurrent VTE (Grade 2B). Remarks: Because aspirin is expected to be much less effective at preventing recurrent VTE than anticoagulants, we do not consider aspirin a reasonable alternative to anticoagulant therapy in patients who want extended therapy. However, if a patient has decided to stop anticoagulants, prevention of recurrent VTE is one of the benefits of aspirin that needs to be balanced against aspirin’s risk of bleeding and inconvenience. Use of aspirin should also be reevaluated when patients stop anticoagulant therapy because aspirin may have been stopped when anticoagulants were started.
Whether and How to Anticoagulate Isolated Distal DVT
13. In patients with acute isolated distal DVT of the leg and (i) without severe symptoms or risk factors for extension (see text), we suggest serial imaging of the deep veins for 2 weeks over anticoagulation (Grade 2C) or (ii) with severe symptoms or risk factors for extension (see text), we suggest anticoagulation over serial imaging of the deep veins (Grade 2C). Remarks: Patients at high risk for bleeding are more likely to benefit from serial imaging. Patients who place a high value on avoiding the inconvenience of repeat imaging and a low value on the inconvenience of treatment and on the potential for bleeding are likely to choose initial anticoagulation over serial imaging.
14. In patients with acute isolated distal DVT of the leg who are managed with anticoagulation, we recommend using the same anticoagulation as for patients with acute proximal DVT (Grade 1B).
15. In patients with acute isolated distal DVT of the leg who are managed with serial imaging, we (i) recommend no anticoagulation if the thrombus does not extend (Grade 1B), (ii) suggest anticoagulation if the thrombus extends but remains confined to the distal veins (Grade 2C), and (iii) recommend anticoagulation if the thrombus extends into the proximal veins (Grade 1B).
Catheter-Directed Thrombolysis for Acute DVT of the Leg
16. In patients with acute proximal DVT of the leg, we suggest anticoagulant therapy alone over CDT (Grade 2C). Remarks: Patients who are most likely to benefit from CDT (see text), who attach a high value to prevention of postthrombotic syndrome (PTS), and a lower value to the initial complexity, cost, and risk of bleeding with CDT, are likely to choose CDT over anticoagulation alone.
Role of Inferior Vena Cava Filter in Addition to Anticoagulation for Acute DVT or PE
17. In patients with acute DVT or PE who are treated with anticoagulants, we recommend against the use of an inferior vena cava (IVC) filter (Grade 1B).
Compression Stocking to Prevent PTS
*18. In patients with acute DVT of the leg, we suggest not using compression stockings routinely to prevent PTS (Grade 2B). Remarks: This recommendation focuses on prevention of the chronic complication of PTS and not on the treatment of symptoms. For patients with acute or chronic symptoms, a trial of graduated compression stockings is often justified.
Whether to Anticoagulate Subsegmental PE
*19. In patients with subsegmental PE (no involvement of more proximal pulmonary arteries) and no proximal DVT in the legs who have a (i) low risk for recurrent VTE (see text), we suggest clinical surveillance over anticoagulation (Grade 2C) or (ii) high risk for recurrent VTE (see text), we suggest anticoagulation over clinical surveillance (Grade 2C). Remarks: Ultrasound (US) imaging of the deep veins of both legs should be done to exclude proximal DVT. Clinical surveillance can be supplemented by serial US imaging of the proximal deep veins of both legs to detect evolving DVT (see text). Patients and physicians are more likely to opt for clinical surveillance over anticoagulation if there is good cardiopulmonary reserve or a high risk of bleeding.
Treatment of Acute PE Out of the Hospital
*20. In patients with low-risk PE and whose home circumstances are adequate, we suggest treatment at home or early discharge over standard discharge (eg, after the first 5 days of treatment) (Grade 2B). Systemic Thrombolytic Therapy for PE
21. In patients with acute PE associated with hypotension (eg, systolic BP <90 mm Hg) who do not have a high bleeding risk, we suggest systemically administered thrombolytic therapy over no such therapy (Grade 2B).
*22. In most patients with acute PE not associated with hypotension, we recommend against systemically administered thrombolytic therapy (Grade 1B).
*23. In selected patients with acute PE who deteriorate after starting anticoagulant therapy but have yet to develop hypotension and who have a low bleeding risk, we suggest systemically administered thrombolytic therapy over no such therapy (Grade 2C). Remarks: Patients with PE and without hypotension who have severe symptoms or marked cardiopulmonary impairment should be monitored closely for deterioration. Development of hypotension suggests that thrombolytic therapy has become indicated. Cardiopulmonary deterioration (eg, symptoms, vital signs, tissue perfusion, gas exchange, cardiac biomarkers) that has not progressed to hypotension may also alter the risk-benefit assessment in favor of thrombolytic therapy in patients initially treated with anticoagulation alone.
Catheter-Based Thrombus Removal for the Initial Treatment of PE
*24. In patients with acute PE who are treated with a thrombolytic agent, we suggest systemic thrombolytic therapy using a peripheral vein over CDT (Grade 2C). Remarks: Patients who have a higher risk of bleeding with systemic thrombolytic therapy and who have access to the expertise and resources required to do CDT are likely to choose CDT over systemic thrombolytic therapy.
*25. In patients with acute PE associated with hypotension and who have (i) a high bleeding risk, (ii) failed systemic thrombolysis, or (iii) shock that is likely to cause death before systemic thrombolysis can take effect (eg, within hours), if appropriate expertise and resources are available, we suggest catheter assisted thrombus removal over no such intervention (Grade 2C). Remarks: Catheter-assisted thrombus removal refers to mechanical interventions, with or without catheter directed thrombolysis.
Pulmonary Thromboendarterectomy for the Treatment of Chronic Thromboembolic Pulmonary Hypertension
*26. In selected patients with chronic thromboembolic pulmonary hypertension (CTEPH) who are identified by an experienced thromboendarterectomy team, we suggest pulmonary thromboendarterectomy over no pulmonary thromboendarterectomy (Grade 2C). Remarks: Patients with CTEPH should be evaluated by a team with expertise in treatment of pulmonary hypertension. Pulmonary thromboendarterectomy is often lifesaving and life-transforming. Patients with CTEPH who are not candidates for pulmonary thromboendarterectomy may benefit from other mechanical and pharmacological interventions designed to lower pulmonary arterial pressure.
Thrombolytic Therapy in Patients With Upper Extremity DVT
27. In patients with acute upper extremity DVT (UEDVT) that involves the axillary or more proximal veins, we suggest anticoagulant therapy alone over thrombolysis (Grade 2C). Remarks: Patients who (i) are most likely to benefit from thrombolysis (see text); (ii) have access to CDT; (iii) attach a high value to prevention of PTS; and (iv) attach a lower value to the initial complexity, cost, and risk of bleeding with thrombolytic therapy are likely to choose thrombolytic therapy over anticoagulation alone.
28. In patients with UEDVT who undergo thrombolysis, we recommend the same intensity and duration of anticoagulant therapy as in patients with UEDVT who do not undergo thrombolysis (Grade 1B).
Management of Recurrent VTE on Anticoagulant Therapy
*29. In patients who have recurrent VTE on VKA therapy (in the therapeutic range) or on dabigatran, rivaroxaban, apixaban, or edoxaban (and are believed to be compliant), we suggest switching to treatment with LMWH at least temporarily (Grade 2C). Remarks: Recurrent VTE while on therapeutic-dose anticoagulant therapy is unusual and should prompt the following assessments: (1) reevaluation of whether there truly was a recurrent VTE; (2) evaluation of compliance with anticoagulant therapy; and (3) consideration of an underlying malignancy. A temporary switch to LMWH will usually be for at least 1 month.
*30. In patients who have recurrent VTE on longterm LMWH (and are believed to be compliant), we suggest increasing the dose of LMWH by about one-quarter to one-third (Grade 2C). Remarks: Recurrent VTE while on therapeutic-dose anticoagulant therapy is unusual and should prompt the following assessments: (1) reevaluation of whether there truly was a recurrent VTE; (2) evaluation of compliance with anticoagulant therapy; and (3) consideration of an underlying malignancy.
CHEST has been developing and publishing guidelines for the treatment of DVT and PE, collectively referred to as VTE, for more than 30 years. CHEST published the last (9th) edition of these guidelines in February 2012 (AT9).1 Since then, a substantial amount of new evidence relating to the treatment of VTE has been published, particularly in relation the use of non-vitamin K oral anticoagulants (NOACs). Moreover, several VTE treatment questions that were not addressed in the last edition have been highlighted. This article focuses on new developments and ongoing controversies in the treatment of VTE, updating recommendations for 12 topics that were included in AT9, and providing recommendations for 3 new topics. The target users of this guideline are clinicians.
