What are the new updates from the CHEST 2021 VTE guidelines?

Antithrombotic Therapy for VTE Disease: Second Update of the CHEST Guideline and Expert Panel Report
Previous recommendation	2021 Update	Rational
No Previous recommendation	4. In patients who are incidentally found to have asymptomatic PE, we suggest the same initial and long-term anticoagulation as for comparable patients with symptomatic PE (weak recommendation, moderate-certainty evidence).	Formal evidence profiles were not created in the 1st update due to a lack of high-quality evidence. The panelists determined that there were no additional high-quality data to further inform the PICO.2 Given the lack of high-quality evidence, and the endorsement of the prior guidance statement, no evidence to-decision framework was undertaken for this PICO.
No Previous Recommendation	5. In patients with cerebral vein/venous sinus thrombosis, we recommend anticoagulation therapy for at least the treatment phase (first 3 months) over no anticoagulant therapy (strong recommendation, low-certainty evidence).	The committee reviewed 1,290 abstracts, from which they selected 62 full texts for review. Studies selected for abstraction and synthesis are detailed in Table 3. Due to the small numbers of subjects in the included studies, confidence intervals around benefit and harm estimates are broad. The panelists determined that the desirable effects of the intervention are large, while undesirable effects were assessed as trivial, and the balance of effects, therefore, favor the intervention, with a low certainty of evidence.
18. In patients with acute DVT of the leg, we suggest not using compression stockings routinely to prevent PTS	6. In patients with acute DVT of the leg we suggest anticoagulant therapy alone over interventional (thrombolytic, mechanical, or pharmacomechanical) therapy (weak recommendation, moderate-certainty evidence).	---
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	9. In selected patients with acute PE who deteriorate after starting anticoagulant therapy but have yet to develop hypotension and who have an acceptable bleeding risk, we suggest systemically administered thrombolytic therapy over no such therapy	While the formal evidence to decision assessment warrants a weak recommendation in favor of anticoagulation the panelists upgraded the guidance to a strong recommendation, placing a very high value on avoiding the potential increase in harm when the magnitude of benefit is variable.
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).	12. In patients with acute DVT of the leg, we recommend against the use of an inferior vena cava (IVC) filter in addition to anticoagulants (strong recommendation, moderate-certainty evidence).	The committee reviewed 155 abstracts, from which they selected 35 full texts for review. The committee determined that there were no additional high-quality data to further inform and utilized the evidence profile from the 1st update (2016). Given the use of the preceding evidence profile and endorsement of the prior guidance statement, no evidence-to-decision framework was undertaken for this guideline.
No Previous Recommendation	13. In patients with acute proximal DVT of the leg and a contraindication to anticoagulation, we recommend the use of an IVC filter (strong recommendation, moderate-certainty evidence).	See above
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).	14. In patients with low-risk PE we recommend outpatient treatment over hospitalization provided access to medications, ability to access outpatient care, and home circumstances are adequate (strong recommendation, low-certainty evidence).	While the formal assessment warrants a weak recommendation in favor of anticoagulation (“suggest”) the panelists upgraded the guidance to a strong recommendation, placing a very high value on avoiding the potential increase in risk of harm (including much greater cost) related to hospitalization even though the magnitude of benefit is similar.
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 2B), dabigatran (Grade 2C), rivaroxaban (Grade 2C), apixaban (Grade 2C), or edoxaban (Grade 2C).	16. In patients with acute VTE in the setting of cancer (“cancer-associated thrombosis”) we recommend an oral Xa inhibitor (apixaban, edoxaban, rivaroxaban) over LMWH for the initiation and treatment phases of therapy (strong recommendation, moderate-certainty evidence).	Remark: Edoxaban and rivaroxaban appear to be associated with a higher risk of gastrointestinal major bleeding than LMWH in patients with CAT and a luminal gastrointestinal malignancy while apixaban does not. Apixaban or LMWH may be the preferred option in patients with luminal GI malignancies.
No Previous Recommendation	17. In patients with confirmed antiphospholipid syndrome being managed with anticoagulant therapy, we suggest adjusted dose VKA (target INR 2.5) over DOAC therapy during the treatment phase (weak recommendation, low-certainty evidence). Remark: Initiating VKA therapy should include an overlapping period of parenteral anticoagulation.	The committee reviewed 921 abstracts, from which they selected 27 full texts for review Studies selected for abstraction and synthesis are detailed in Table 12. The panelists determined that the desirable effects of the intervention are small in magnitude while the undesirable effects are large. Overall, the panelists rated the balance of effects as probably favoring the comparison, with a low certainty of evidence.
No Previous Recommendation	18. In patients with superficial venous thrombosis (SVT) of the lower limb at increased risk of clot progression to DVT or PE (see text), we suggest the use of anticoagulation for 45 days over no anticoagulation (Weak recommendation, moderate-certainty evidence).	The committee reviewed 252 abstracts, from which they selected 26 full texts for review. Studies selected for abstraction and synthesis are detailed in Tables 13-16. The panelists determined that the desirable effects of the intervention are small in magnitude while the undesirable effects are trivial. Overall, the panelists rated the balance of effects as probably favoring the intervention, with a moderate certainty of evidence.
No Previous Recommendation	19. In patients with SVT who are treated with anticoagulation, we suggest fondaparinux 2.5 mg daily over other anticoagulant treatment regimens such as (prophylactic or therapeutic) dose of LMWH (weak recommendation, low-certainty evidence).	See Above
No Previous Recommendation	20. In patients with SVT who refuse or are unable to use parenteral anticoagulation, we suggest rivaroxaban 10 mg daily as a reasonable alternative for fondaparinux 2.5 mg daily (weak recommendation, low-certainty evidence).	See above
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).	21. In patients with acute VTE who do not have a contraindication we recommend a 3-month treatment phase of anticoagulation (strong recommendation, moderate-certainty evidence). 22. In patients with VTE diagnosed in the setting of a major transient risk factor (see text), we recommend against offering extended-phase anticoagulation (strong recommendation, moderate-certainty evidence). 23. In patients with VTE diagnosed in the setting of a minor transient risk factor (see text), we suggest against offering extended-phase anticoagulation (weak recommendation, moderate-certainty evidence).	Remark: Upon completion of the 3-month treatment phase of therapy, all patients should be assessed for extended-phase therapy.
No Previous Recommendation	25. In patients with VTE diagnosed in the absence of transient risk factor (unprovoked VTE or provoked by a persistent risk factor) who cannot receive a DOAC, we suggest offering extended-phase anticoagulation with a VKA (weak recommendation, moderate-certainty evidence).	The recommendation to offer extended-phase anticoagulation would not automatically imply that all patients with unprovoked VTE receive extended therapy. Patient preference and predicted risk of recurrent VTE or bleeding should also influence the decision to proceed with, or continue, extended-phase anticoagulation therapy. Patients who receive extended-phase anticoagulation should have this decision reevaluated at least on an annual basis, and at times of significant change in health status. Extended phase anticoagulation does not have a pre-defined stop date. However, studies of extended-phase anticoagulation followed patients for durations of about 2-4 years. While most patients in these studies did not stop anticoagulation therapy at the end of follow-up, the risk:benefit balance of continuing extended anticoagulation therapy beyond this time is uncertain.
No Previous Recommendation	26. In patients offered extended phase anticoagulation, we suggest the use of reduced dose apixaban or rivaroxaban over full dose apixaban or rivaroxaban (weak recommendation, very low-certainty evidence).	Remark: Reduced dose refers to apixaban 2.5mg twice daily and rivaroxaban 10mg once daily.
No Previous Recommendation	27. In patients offered extended phase anticoagulation, we recommend reduced dose DOAC over aspirin or no therapy (strong recommendation, low certainty evidence) and suggest rivaroxaban over aspirin (weak recommendation, moderate-certainty evidence).	While the formal evidence to decision assessment warrants a weak recommendation in favor of anticoagulation, the panelists upgraded the guidance to a strong recommendation, placing a very high value on an uncertain but potentially life-preserving benefit. Reduced dose refers to apixaban 2.5mg twice daily and rivaroxaban 10mg once daily. Rivaroxaban is the only DOAC to be directly compared to aspirin for secondary prevention of VTE. Several other DOACs, as well as warfarin, are also acceptable for secondary prevention (extended-phase therapy) after VTE.

References:

Stevens SM, Woller SC, Baumann Kreuziger L, et al. Antithrombotic therapy for vte disease: second update of the chest guideline and expert panel report - executive summary. Chest. Published online July 31, 2021:S0012-3692(21)01507-5.