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................................................................. 8.1 Assessment of venous thromboembolism recurrence risk The risk for recurrent VTE after discontinuation of treatment is related to the features of the index PE (or, in the broader sense, VTE) event. A study, which followed patients after a first episode of acute PE, found that the recurrence rate after discontinuation of treatment was 2.5% per year after PE associated with transient risk factors, compared with 4.5% per year after PE occurring in the absence of known cancer, known thrombophilia, or any transient risk factor.331 Similar observations were made in other prospective studies in patients with DVT.337 Advancing the concept further, randomized anticoagulation trials over the past 15 years, which have focused on secondary VTE prevention, have classified patients into distinct groups based on their risk of VTE recurrence after discontinuation of anticoagulant treatment. In general, these groups are: (i) patients in whom a strong (major) transient or reversible risk factor, most commonly major surgery or trauma, can be identified as being responsible for the acute (index) episode; (ii) patients in whom the index episode might be partly explained by the presence of a weak (minor) transient or reversible risk factor, or if a non-malignant risk factor for thrombosis persists; (iii) patients in whom the index episode occurred in the absence of any identifiable risk factor (the present Guidelines avoid terms such as ‘unprovoked’ or ‘idiopathic’ VTE); (iv) patients with one or more previous episodes of VTE, and those with a major persistent pro-thrombotic condition such as antiphospholipid antibody syndrome; and (v) patients with active cancer.338

Table 11 shows examples of transient/reversible and persistent risk factors for VTE, classified by the risk of long-term recurrence. As active cancer is a major risk factor for recurrence of VTE, but also for bleeding while on anticoagulant treatment,339 section 8.4 is specifically dedicated to the management of PE in patients with cancer. Overall, assessment of the VTE recurrence risk after acute PE, in the absence of a major transient or reversible risk factor, is a complex issue. Beyond the examples listed in Table 11, patients who are carriers of some forms of hereditary thrombophilia, notably those with confirmed deficiency of antithrombin, protein C, or protein S, and patients with homozygous factor V Leiden or homozygous prothrombin G20210A mutation, are often candidates for indefinite anticoagulant treatment after a first episode of PE occurring in the absence of a major reversible risk factor. In view of these possible implications, testing for thrombophilia (including antiphospholipid

Table 11 Categorization of risk factors for venous thromboembolism based on the risk of recurrence over the longterm

Estimated risk for long-term recurrencea Risk factor category for index PEb Examplesb

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 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 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

Non-malignant persistent risk factors bowel disease • Active autoimmune disease

No risk factor

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 ©ESC 2019

PE = pulmonary embolism; VTE = venous thromboembolism. aIf anticoagulation is discontinued after the first 3 months (based on data from Baglin et al.340 and Iorio et al.341). bThe categorization of risk factors for the index VTE event is in line with that proposed by the International Society on Thrombosis and Haemostasis.338 The present Guidelines avoid terms such as ‘provoked’, ‘unprovoked’, or ‘idiopathic’ VTE. Downloaded from academic.oup.com/eurheartj/article/41/4/543/5556136 by guest on 07 October 2026