Update on Antithrombotic Therapy for VTE Disease

January 26, 2022

Written by Clay Smith

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We dig into the new VTE update on antithrombotic therapy in this post.

Why does this matter?
This is a second update (first in 2016) of the 9th edition (in 2012) of the this publication. There are new things for us here, many of which have a strong evidence base. This is the standard of care for VTE. Let’s get after it!

VTE – Very Thorough Evidence!

There are 29 statements. This is a bit longer (who am I kidding…WAY longer) than usual, but each statement has some relevance to the ED, and we really have to know this stuff.

1. 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 (weak recommendation, moderate-certainty evidence) or (ii) with severe symptoms or risk factors for extension (see text), we suggest anticoagulation over serial imaging of the deep veins (weak recommendation, low-certainty evidence).
   Comment: A recent large retrospective study found that if we are using DOACs vs LMWH/warfarin, the scales may tip toward treatment. Anticoagulation if… 1) D-dimer positive (especially if very high for no good reason); 2) thrombosis extensive (> 5 cm long clot, multiple veins, > 7 mm diameter); 3) clot close to the proximal veins; 4) unprovoked DVT; 5) active cancer; 5) history of VTE; 6) inpatient; 7) has COVID-19; 8) severe symptoms; 9) does not want repeat ultrasound.

2. In patients with acute isolated distal DVT of the leg who are treated with serial imaging, we (i) recommend no anticoagulation if the thrombus does not extend (strong recommendation, moderate-certainty evidence), (ii) suggest anticoagulation if the thrombus extends but remains confined to the distal veins (weak recommendation, very low-certainty evidence), and (iii) recommend anticoagulation if the thrombus extends into the proximal veins (strong recommendation, moderate-certainty evidence).
   Comment: This is more of an outpatient follow up issue but could be something we face in the ED.

3. In patients with subsegmental pulmonary embolism (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 (weak recommendation, low-certainty evidence) or (ii) high risk for recurrent VTE (see text), we suggest anticoagulation over clinical surveillance (weak recommendation, low-certainty evidence).
   Comment: In a very recent study of patients with SSPE, not included in this guideline, the rate of recurrent VTE was higher than expected, 3.1%, especially if multiple SSPEs or age > 65 years. By the way, “high risk” means: 1) hospitalized or reduced mobility; 2) active cancer; 3) no reversible risk factor like recent surgery; 4) pregnancy.

4. In patients who are incidentally found to have asymptomatic PE, we suggest the same initiation and treatment phase anticoagulation as for comparable patients with symptomatic PE (weak recommendation, moderate-certainty evidence).
   Comment: That makes sense.

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).
   Comment: We reviewed CVT recently. Brain clots are bad.

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).
   Comment: This contrasts with select cases of primary upper extremity DVT due to thoracic outlet obstruction from repetitive activity (such as baseball pitching) – so called Paget-Schroetter syndrome – which may benefit from thrombolysis +/- venoplasty with thoracic outlet decompression in select cases. I consult vascular in young otherwise healthy, active people with acute, primary UE DVT. But leave people’s legs alone – meds only.

7. 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 (weak recommendation, low-certainty evidence).
   Comment: This is so-called massive PE. These need lytics.

8. In most patients with acute PE not associated with hypotension, we recommend against systemically administered thrombolytic therapy (strong recommendation, low-certainty evidence).
   Comment: This is so-called submassive PE, for which the evidence leads away from using alteplase. Long-term follow up of the PEITHO study, did not find mortality benefit, reduced dyspnea, or reduced chronic thromboembolic pulmonary hypertension.

9. In selected patients with acute PE who deteriorate (see remarks) 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 (weak recommendation, low-certainty evidence).
   Comment: This is why risk stratification, with a tool like the PE-SCORE, is so important after diagnosing PE. We know some patients will get worse, and it’s best for them to do so in an ICU setting.

10. In patients with acute PE who are treated with a thrombolytic agent, we suggest systemic thrombolytic therapy using a peripheral vein over catheter-directed thrombolysis (CDT) (weak recommendation, low- certainty evidence).
    Comment: We cover catheter-based treatment options in this post.

11. In patients with acute PE associated with hypotension who also 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 (weak recommendation, low-certainty evidence).
    Comment: It’s important to recognize, there is catheter-based thrombolysis and catheter-based embolectomy. This is referring to the latter, whereas statement 10 refers to the former.

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).
    Comment: Deciding on IVC filters is not an ED thing, but we do need to know that IVC filters do not offer protection from recurrent PE, even fatal PE. Don’t have false reassurance when a patient has an IVC filter and neglect to work up PE in patients with the right clinical scenario. One might ask, “Then why place one?” See the next point.

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).
    Comment: IVC filters have a place. This is it. Use retrievable filters.

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).
    Comment: Although possible, in practice this remains uncommon, with < 5% of all PE patients actually sent home.

15. In patients with VTE (DVT of the leg or PE) we recommend apixaban, dabigatran, edoxaban, or rivaroxaban over vitamin K antagonist (VKA) as treatment-phase (first 3 months) anticoagulant therapy (strong recommendation, moderate-certainty evidence).
    Comment: This JF review has a handy table for when to use what agent.

16. In patients with acute VTE in the setting of cancer (cancer-associated thrombosis) we recommend an oral Xa inhibitor (apixaban, edoxaban, rivaroxaban) over low molecular weight heparin (LMWH) for the initiation and treatment phases of therapy (strong recommendation, moderate-certainty evidence).
    Comment: This is new. It used to be LMWH. The caveat is that edoxaban and rivaroxaban may increase bleeding risk with luminal GI malignancies. Apixaban or LMWH may be the preferred options in patients with such malignancies.

17. In patients with confirmed antiphospholipid syndrome being treated with anticoagulant therapy, we suggest adjusted dose VKA (target INR 2.5) over direct oral anticoagulant (DOAC) therapy during the treatment phase (weak recommendation, low- certainty evidence).
    Comment: This is an instance where warfarin may be better than DOACs.

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).
    Comment: This was news to me. Except for clots caused by a recent IV, there is benefit to treating superficial clots, especially if, “1) extensive SVT, 2) involvement above the knee, particularly if close to the saphenofemoral junction, 3) severe symptoms, 4) involvement of the greater saphenous vein, 5) history of VTE or SVT, 6) active cancer, 7) recent surgery.” Be sure to rule out proximal DVT in these patients, as it is often found concomitantly. See the next two points for treatment options.

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) LMWH (weak recommendation, low-certainty evidence).

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).

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).
    Comment: In the ED, we can tell patients they will need anticoagulation for at least 3 months, maybe longer. Statements 22-28 all deal with deciding when to use extended anticoagulation.

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).
    Comment: This is “provoked VTE.” When there is a good reason, like major surgery > 30 minutes, hospitalized and bedbound for ≥3 days, 3 months is the duration.

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).
    Comment: This is a unique group, like surgery <30 minutes, estrogen therapy, in which clot is “provoked” but by a minor trigger. They recommend > 3 months for these patients.

24. In patients with VTE diagnosed in the absence of transient provocation (unprovoked VTE or provoked by persistent risk factor), we recommend offering extended-phase anticoagulation with a DOAC (strong recommendation, moderate-certainty evidence).
    Comment: Definitely > 3 months if unprovoked VTE. DOACs are first line.

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).
    Comment: DOACs first, but if you can’t use them, VKA.

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).
    Comment: We are always walking the line between treatment benefit and bleeding risk. Some evidence suggests a reduced dose still gives benefit but at a lower bleeding risk.

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).
    Comments: Aspirin isn’t an alternative to anticoagulation, but as the next point states, it is better than not using aspirin at all in certain cases.

28. 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 (weak recommendation, low-certainty evidence).
    Comment: See above point.

29. In patients with acute DVT of the leg, we suggest against using compression stockings routinely to prevent post-thrombotic syn
    drome (PTS) (weak recommendation, low-certainty evidence).
    Comment: Not only are compression stockings not stylish, they don’t prevent this bad outcome.

Source
Antithrombotic Therapy for VTE Disease: Second Update of the CHEST Guideline and Expert Panel Report. Chest. 2021 Dec;160(6):e545-e608. doi: 10.1016/j.chest.2021.07.055. Epub 2021 Aug 2.