Who needs extended anticoagulation?

Although the risk of VTE recurrence is higher in patients with no identifiable risk factors, recurrence rates in patients with minor transient or minor persistent factors can be equivalent to – and as serious as – those with VTE with no predisposing factors.1 Therefore, these patients may also benefit from extended anticoagulation therapy.1

Incidences of recurrent VTE according to baseline risk factor profile1

Adapted from Prins MH et al. Blood Adv 2018.1

Categorisation of risk factors for VTE based on the risk of recurrence over the long-term2
Estimated risk for long-term recurrence* Risk factor category for index PE Examples
Low (<3% per year) Major transient or reversible factors associated with >10-fold increased risk for the index VTE event (compared to patients without the risk factor)
  • Surgery with general anaesthesia for >30 min
  • Confined to bed in hospital (only “bathroom privileges”) for ≥3 days due to an acute illness, or acute exacerbation of a chronic illness
  • Trauma with fractures
Intermediate (3–8% per year) Transient or reversible factors associated with ≤10-fold increased risk for (index) VTE
  • Minor surgery (general anaesthesia for <30 min)
  • Admission to hospital for <3 days with an acute illness
  • Oestrogen therapy / contraception
  • Pregnancy or puerperium
  • Confined to bed out of hospital for ≥3 days with an acute illness
  • Leg injury (without fracture) associated with reduced mobility for ≥3 days
  • Long-haul flight
Non-malignant persistent risk factors
  • Inflammatory bowel disease
  • Active autoimmune disease
No identifiable risk factors
High (>8% per year)
  • Active cancer
  • One or more previous episodes of VTE in the absence of a major transient or reversible factor
  • Antiphospholipid antibody syndrome

Adapted from Konstantinides S et al. Eur Heart J 2019.2
* If anticoagulation is discontinued after the first 3 months.

NOACs are not recommended / contraindicated during pregnancy.3–6
The efficacy and safety of some NOACs, including apixaban in the treatment of DVT, treatment of PE and prevention of recurrent DVT and PE in patients with active cancer have not been established.3,5,6
NOACs are not recommended in patients with a history of thrombosis who are diagnosed with antiphospholipid syndrome.3–6

Risk of VTE recurrence after cessation of anticoagulation varies according to the index cause.7 However, secondary risk factors (e.g. proximal vs. distal location and gender) can also contribute to the risk of VTE recurrence to varying degrees.7

ESC recommendations for the regimen and duration of anticoagulation after PE in non-cancer patients2
Recommendation Class Level
Therapeutic anticoagulation for ≥3 months is recommended for all patients with PE. I A
Patients in whom discontinuation of anticoagulation after 3 months is recommended
For patients with first PE / VTE secondary to a major transient / reversible risk factor, discontinuation or therapeutic oral anticoagulation is recommended after 3 months. I B
Patients in whom extension of anticoagulation beyond 3 months is recommended
Oral anticoagulant treatment of indefinite duration is recommended for patients presenting with recurrent VTE (that is, with at least one previous episode of PE or DVT) not related to a major transient or reversible risk factor. I B
Oral anticoagulant treatment with a VKA for an indefinite period is recommended for patients with antiphospholipid syndrome. I B
Patients in whom extension of anticoagulation beyond 3 months should be considered*
Extended oral anticoagulation of indefinite duration should be considered for patients with a first episode of PE and no identifiable risk factor. IIa A
Extended oral anticoagulation of indefinite duration should be considered for patients with a first episode of PE associated with a persistent risk factor other than antiphospholipid antibody syndrome. IIa C
Extended oral anticoagulation of indefinite duration should be considered for patients with a first episode of PE associated with a minor transient or reversible risk factor. IIa C
NOAC dose in extended anticoagulation
If extended oral anticoagulation is decided after PE in a patient without cancer, a reduced dose of the NOACs apixaban (2.5 mg BD) or rivaroxaban (10 mg OD) should be considered after 6 months of therapeutic anticoagulation. IIa A
Extended treatment with alternative antithrombotic agents
In patients who refuse to take or are unable to tolerate any form of oral anticoagulants, aspirin or sulodexide may be considered for extended VTE prophylaxis. IIb B
Follow-up of the patient undergoing anticoagulation
In patients who receive extended anticoagulation, it is recommended that their drug tolerance and adherence, hepatic and renal function, and bleeding risk be reassessed at regular intervals. I C

Adapted from Konstantinides S et al. Eur Heart J 2019.2
* Bleeding risk should be assessed to identify and treat modifiable bleeding risk factors, and it may influence decision-making on the duration and regimen / dose of anticoagulant treatment.
† If dabigatran or edoxaban is chosen for extended anticoagulation after PE, the dose should remain unchanged, as reduced-dose regimens were not investigated in dedicated extension trials.
‡ Especially for patients receiving NOACs.

Abbreviations

  • CPRD = Clinical Practice Research Datalink
  • DVT = Deep Vein Thrombosis
  • ESC = European Society of Cardiology
  • NOAC = Non-vitamin K antagonist Oral Anticoagulant
  • OAC = Oral Anticoagulant
  • PE = Pulmonary Embolism
  • VTE = Venous Thromboembolic Events

  1. Prins MH, Lensing AW, Prandoni P, et al. Risk of recurrent venous thromboembolism according to baseline risk factor profiles. Blood Adv 2018;2:788–96. https://doi.org/10.1182/bloodadvances.2018017160; PMID: 29632234.
  2. Konstantinides S, Meyer G, Becattini C, et al. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society: The Task Force for the diagnosis and management of acute pulmonary embolism of the European Society of Cardiology. Eur Heart J 2019;00:1–61. https://doi.org/10.1093/eurheartj/ehz405; PMID: 31473594.
  3. Apixaban Summary of Product Characteristics.
  4. Rivaroxaban Summary of Product Characteristics.
  5. Dabigatran Summary of Product Characteristics.
  6. Edoxaban Summary of Product Characteristics.
  7. Kearon C, Akl EA. Duration of anticoagulant therapy for deep vein thrombosis and pulmonary embolism. Blood 2014;123:1794–801. https://doi.org/10.1182/blood-2013-12-512681; PMID: 24497538.

December 2019
PP-ELI-GBR-6095