long-term anticoagulation for secondary prevention of pulmonary embolism (PE) or deep vein thrombosis (DVT)

Last edited 05/2020 and last reviewed 01/2021

extended phase of anticoagulation (beyond first 3-6 months)

Risks and benefits of continuing anticoagulation should be assessed on a case-by-case basis, balancing risk of recurrence against bleeding risk, taking into account patients' preferences and compliance.

  • the main aim of therapy beyond 3-6 months is to continue to suppress thrombin generation in order to prevent recurrent venous thromboembolism (VTE)
    • risk of VTE recurrence within 10 years after the first episode is estimated to be more than 30%
    • patients with a first symptomatic unprovoked DVT are at higher risk of recurrence than those with a first unprovoked PE (1,2,3)

Therapeutic options for long term treatment of DVT/PE include:

  • vitamin K antagonists
    • VKA [target international normalized ratio (INR) 2.0- 3.0] treatment reduce the relative risk of recurrent VTE by 88 %, but they are associated with 2.6 fold increase in major bleeding compared with placebo
    • low-intensity (INR 1.5- 1- 9) anticoagulation has similar risk of major bleeding, hence standard intensity anticoagulation should be used for long term therapy of VTE.
    • NICE recommendation:
      • offer a VKA beyond 3 months to patients with an unprovoked PE, taking into account the patient's risk of VTE recurrence and whether they are at increased risk of bleeding. Discuss with the patient the benefits and risks of extending their VKA treatment
      • consider extending the VKA beyond 3 months for patients with unprovoked proximal DVT if their risk of VTE recurrence is high and there is no additional risk of major bleeding. Discuss with the patient the benefits and risks of extending their VKA treatment (4)

  • LMWH/Fondaparinux
    • LMWH has been shown to be as effective as VKA in the reduction of recurrent VTE. Risk of major bleeding is reduced when compared to VKA
    • although there is limited evidence, fondaparinux is also thought to be as effective as LMWH in the prevention of recurrent VTE

  • Direct Oral Anticoagulants (DOACs)
    • in the absence of contraindications, DOACs should be preferred as first line anticoagulant therapy in non-cancer patients
    • low-dose apixaban and rivaroxaban have shown their benefit in this setting

  • aspirin
    • may be considered for extended treatment if long term anticoagulation is contraindicated or (1,2,3,4).

Regular (at least yearly) assessment of compliance and benefit/risk balance should be performed in patients on extended treatment (1).

NICE suggest (4):

  • assess and discuss the benefits and risks of continuing, stopping or changing the anticoagulant with people who have had anticoagulation treatment for 3 months (3 to 6 months for people with active cancer) after a proximal DVT or PE
  • consider stopping anticoagulation treatment 3 months (3 to 6 months for people with active cancer) after a provoked DVT or PE if the provoking factor is no longer present and the clinical course has been uncomplicated
  • consider using the HAS-BLED score to assess the risk of major bleeding in people having anticoagulation treatment for unprovoked proximal DVT or PE. Discuss stopping anticoagulation if the HAS-BLED score is 4 or more and cannot be modified
  • for people who do not have renal impairment, active cancer, established triple positive antiphospholipid syndrome or extreme body weight (less than 50 kg or more than 120 kg):
    • offer continued treatment with the current anticoagulant if it is well tolerated or
    • if the current treatment is not well tolerated, or the clinical situation or person's preferences have changed, consider switching to apixaban if the current treatment is a direct-acting anticoagulant other than apixaban
  • for people with renal impairment, active cancer, established triple positive antiphospholipid syndrome or extreme body weight (less than 50 kg or more than 120 kg), consider carrying on with the current treatment if it is well tolerated
  • if anticoagulation treatment fails follow the recommendation on treatment failure
  • for people who decline continued anticoagulation treatment, consider aspirin 75 mg or 150 mg daily
  • review general health, risk of VTE recurrence, bleeding risk and treatment preferences at least once a year for people taking long-term anticoagulation treatment or aspirin.

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