Apixaban for Extended Anticoagulation (APIDULCIS)

APIDULCIS: Extended Anticoagulation With Low-dose Apixaban After a Standard Course Anticoagulation in Patients With a First Venous Thromboembolism Who Have Positive D-dimer

The study aims at optimizing the long-term and extended management of patients with a first episode of venous thromboembolism (proximal deep vein thrombosis with or without pulmonary embolism) (VTE). Patients at high risk of recurrence (with altered D-dimer test), who had received anticoagulation (whatever the drug used) for 12-15 months after the first episode of thrombosis, will be treated with Apixaban 2,5 mg x 2 for 18 months as extended treatment. Patients at low risk, with normal D-dimer test, will stop anticoagulation definitely.

This prospective cohort study aims to assess the efficacy and safety of a management procedure to decide on giving or not an extended anticoagulation (administering apixaban 2 2.5 mg twice daily ) to outpatients with a single episode of proximal deep vein thrombosis of the lower limbs and/or pulmonary embolism who had received 12-15 months of anticoagulation (whatever the anticoagulant drug used). The study seeks to assess whether a management procedure involving D-dimer testing assessment can identify a subset of subjects at low risk of recurrence in whom an extended anticoagulation can be safely avoided.

Inclusion Criteria:

• First unprovoked Venous Thromboembolic Event
• Venous Thromboembolic events associated with one or more risk factors that are no longer present
• Age older than 18 or younger than 75 years
• Capacity to give written informed consent

Exclusion Criteria:

• A) Exclusion criteria regarding the index event

• Events usually associated with low risk of recurrence

• Deep vein thrombosis/ Pulmonary embolism occurred within 3 months from major surgery or major trauma

• Isolated Distal deep vein thrombosis (thrombosis of calf veins)

• Events associated with a very high risk of recurrence or occurrence of life-threatening recurrent events

  • Pulmonary Embolism episode with shock or life-threatening
  • Isolated pulmonary embolism with a systolic pulmonary artery pressure > 60 mmHg at presentation
  • Deep vein thrombosis/ Pulmonary embolism associated with active cancer, antiphospholipid syndrome or long-standing medical illnesses
  • More than one idiopathic event

• Index venous thromboembolic event in different sites than deep veins of the lower limbs or pulmonary arteries

B) Exclusion criteria present at the moment of patients' screening:

• Age younger than 18 or older than 75 years

• More documented unprovoked venous thromboembolic episodes

• Pregnancy or puerperium

• Severe post-thrombotic syndrome (≥ 15 points at the Villalta score)

• Solid neoplasia or blood disease in active phase or requiring chemotherapy/radiotherapy

• All the clinical conditions requiring prolonged treatment with Low Molecular Weight Heparin

• Presence of overt, active chronic diseases (i.e. inflammatory bowel disease)

• Known serious thrombophilic alterations:

  • deficiencies of natural anticoagulants (Antithrombin, Protein C, Protein S)
  • homozygosity for Factor V Leiden or Factor II G20210A mutations
  • double heterozygosity

• Presence of antiphospholipid syndrome

• Presence of vein cava filter

• Concomitant conditions (such as atrial fibrillation) requiring indefinite anticoagulation

• Severe cardio-respiratory insufficiency (NYHA 3 or 4)

• Any absolute contraindications to anticoagulation treatment

• Any other contraindications to Apixaban as per local SmPC

• Life expectancy shorter than 1 year

• Refuse interruption of anticoagulation to perform serial D-dimer assessment

• Geographically inaccessible location

• Inability or refusal to give consent