Women who met two or more criteria and all men were classified as high risk.
Per protocol, low risk patients were to discontinue anticoagulants (intervention arm), whereas anticoagulant management in high risk patients was left to the discretion of the clinicians and patients (observation arm).
Index VTE associated with minor or weak risk factors such as travel, exogenous oestrogen, minor immobilisation, or minor surgery was considered unprovoked as it is unclear if the risk of recurrence in “weakly provoked” VTE is low enough to discontinue anticoagulants.12 Objective confirmation of index major VTE comprised either deep vein thrombosis demonstrated with a non-compressible segment in the popliteal vein or more proximal leg veins on compression venous ultrasonography and/or pulmonary embolism demonstrated on a high probability perfusion scan21 or a segmental or more proximal pulmonary artery filling defect on computed tomography (CT) pulmonary angiography.
Index VTE had to have been managed for 5-12 months with an appropriate anticoagulant treatment, including initial treatment with either unfractionated heparin, low molecular weight heparin, rivaroxaban, or apixaban, followed by 5-12 months of oral anticoagulant treatment with vitamin K antagonists (target international normalised ratio 2-3), dabigatran, rivaroxaban, apixaban, or edoxaban.
We previously derived a clinical decision rule to identify patients at low risk of recurrent VTE who could discontinue anticoagulants.15 The clinical decision rule, HERDOO2, identifies women with one or fewer of the four following criteria as being at low risk of recurrent VTE: Hyperpigmentation, Edema, or Redness in either leg; D-dimer level ≥250 μg/L during treatment with anticoagulants; Obesity with body mass index ≥30; and Older age, ≥65 years (fig 1).15 No subgroup of men could be identified as low risk for recurrent VTE.
Before adopting a clinical decision rule in clinical practice it should be prospectively validated in multiple clinical settings.17 As such, we validated the HERDOO2 clinical decision rule in a multinational prospective cohort management study.
After short term oral anticoagulant treatment, the risk of recurrent VTE after discontinuing anticoagulants is variable, depending on the presence or absence of provoking factors at the time of the initial event.
Participants were then followed for one year for recurrent VTE and major bleeding.
All patients provided written informed consent before participation.
Per protocol, low risk women were to discontinue oral anticoagulant treatment, whereas continuation of anticoagulation in men and high risk women was left to the discretion of the clinicians and patients.
We also obtained baseline results for bilateral leg compression ultrasonography and either a ventilation-perfusion scan or perfusion only scan or CT pulmonary angiography.