Literature Review: Acute Management of DVT

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Guideline Recommendations

ACCP Guidelines (2021)

The American College of Chest Physicians emphasizes the use of DOACs over warfarin in most non-cancer patients (Grade 2B). In cancer-associated PE, LMWH is preferred (Grade 2C). Recommendations include three months of anticoagulation for provoked PE, with extended therapy considered in unprovoked PE if there’s a low bleeding risk (Grade 2B).

• 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).
• 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).
• 8. In most patients with acute PE not associated with hypotension, we recommend against systemically administered thrombolytic therapy (strong recommendation, low-certainty evidence).
• 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).
• 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, lowcertainty evidence).
• 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 catheterassisted thrombus removal over no such intervention (weak recommendation, low-certainty evidence).
• 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)
• 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).
• 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)

ESC Guidelines (2019)

The European Society of Cardiology advocates for DOACs as first-line therapy in non-cancer patients, allowing for more straightforward management. Individualized treatment duration is advised based on risk factors and patient preference. Thrombolytic therapy may be considered in hemodynamically unstable patients, and a patient-centered approach is encouraged.

ASH Guidelines (2020)

The American Society of Hematology underscores shared decision-making in the choice of anticoagulant, often favoring DOACs over VKAs unless contraindicated. The guidelines also contemplate the use of aspirin after completion of anticoagulation in select patients (Grade 2C), emphasizing patient-specific considerations and ongoing reassessment. Additional Recommendations are below

• Recommendation 3 For patients with DVT and/or PE, the ASH guideline panel suggests using DOACs over VKAs (conditional recommendation based on moderate certainty in the evidence of effects ).
  • Remarks: This recommendation may not apply to certain subgroups of patients, such as those with renal insufficiency (creatinine clearance ,30 mL/min), moderate to severe liver disease, or antiphospholipid syndrome.
• Recommendation 4 For patients with DVT and/or PE, the ASH guideline panel does not suggest 1 DOAC over another (conditional recommendation based on very low certainty in the evidence of comparative effects ).
  • Remarks: Factors such as a requirement for lead-in parenteral anticoagulation, once- vs twice-daily dosing, and out-of-pocket cost may drive the selection of specific DOACs. Other factors, such as renal function, concomitant medications (eg, need for a concomitant drug metabolized through CYP3A4 enzymes or P-glycoprotein), and the presence of cancer, may also impact DOAC choice.
• Recommendation 5 In most patients with proximal DVT, the ASH guideline panel suggests anticoagulation therapy alone over thrombolytic therapy in addition to anticoagulation (conditional recommendation based on low certainty in the evidence of effects ).
  • Remarks: Thrombolysis is reasonable to consider for patients with limb-threatening DVT (phlegmasia cerulea dolens) and for selected younger patients at low risk for bleeding with symptomatic DVT involving the iliac and common femoral veins (higher risk of more severe PTS). Patients in these categories who value rapid resolution of symptoms, are averse to the possibility of PTS, and accept the added risk of major bleeding may prefer thrombolysis. The use of thrombolysis should be rare for patients with DVT limited to veins below the common femoral vein.
• Recommendation 6 For patients with PE and hemodynamic compromise, the ASH guideline panel recommends using thrombolytic therapy followed by anticoagulation over anticoagulation alone (strong recommendation despite low certainty in the evidence of effects ).
  • Remarks: Strong recommendations based on low certainty in the evidence of effects are exceptional. In this case, the high mortality of patients with PE and hemodynamic compromise, as well as the potential lifesaving effect of thrombolytics, warranted a strong recommendation. This exception is in accordance with the exceptional circumstances that allow strong recommendations based on low-certainty evidence in the GRADE ASH rules
• Recommendation 7 For patients with PE with echocardiography and/or biomarkers compatible with right ventricular dysfunction but without hemodynamic compromise (submassive PE), the ASH guideline panel suggests anticoagulation alone over the routine use of thrombolysis in addition to anticoagulation (conditional recommendation based on low certainty in the evidence of effects ).
  • Remarks: Thrombolysis is reasonable to consider for younger patients with submassive PE at low risk for bleeding. Patients with submassive PE should be monitored closely for the development of hemodynamic compromise
• Recommendations 12, 13, and 14 For primary treatment of patients with DVT and/or PE, whether provoked by a transient risk factor (Recommendation 12) or a chronic risk factor (Recommendation 13) or unprovoked (Recommendation 14), the ASH guideline panel suggests using a shorter course of anticoagulation for primary treatment (3-6 months) over a longer course of anticoagulation for primary treatment (6-12 months) (conditional recommendations based on moderate certainty in the evidence of effects

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Landmark Trials

RE-COVER and RE-COVER II Trials (Dabigatran)

These trials demonstrated the non-inferiority of dabigatran to warfarin in acute VTE treatment, including PE. Patients were initially treated with a parenteral anticoagulant before transitioning to dabigatran. The trials found similar efficacy and bleeding profiles between the two treatments, establishing dabigatran as a viable alternative to warfarin.

EINSTEIN-PE Trial (Rivaroxaban)

The EINSTEIN-PE trial showcased rivaroxaban’s non-inferiority to the standard treatment of enoxaparin followed by warfarin in acute PE. Rivaroxaban provided a single-drug approach without the need for initial parenteral therapy, simplifying treatment without increased bleeding risk. This has influenced the preference for rivaroxaban in suitable patients.

AMPLIFY Trial (Apixaban)

The AMPLIFY trial established apixaban’s non-inferiority to enoxaparin/warfarin in acute PE treatment, with the added benefit of reduced major bleeding. The simplified treatment regimen of apixaban, without the need for initial parenteral therapy, makes it an attractive option for many patients, balancing efficacy and safety.

Hokusai-VTE Trial (Edoxaban)

The Hokusai-VTE trial demonstrated edoxaban’s non-inferiority to warfarin in treating VTE, including severe PE, with less bleeding. Unlike other DOACs, edoxaban requires initial parenteral therapy, catering to a wide range of patients and clinical scenarios. The trial’s inclusion of severe PE patients adds to its significance in guiding therapy.