Introduction: The incidence of pulmonary embolism (PE) has been increasing, but its case-fatality rate is decreasing over time, suggesting overdiagnosis, a lesser severity of the illness and/or improvements in treatment strategies. Approximately 10-14% of all diagnosed PE are isolated to the subsegmental vessels. The risk of recurrent venous thromboembolism (VTE) in patients with an acute subsegmental pulmonary embolism (SSPE), managed with or without anticoagulant therapy, remains poorly understood.

Methods and analysis: This is an observational, retrospective cohort study of adult patients diagnosed with an acute isolated SSPE (single or multiple) at The Ottawa Hospital, Ontario, Canada, from June 01, 2019, to August 31, 2022. Data on diagnosis and follow-up were collected through a retrospective review of the medical records. Among inclusion criteria, no selection was made on provoking factors or on presence/absence of symptoms at presentation. We excluded those patients with concomitant diagnosis of deep vein thrombosis (DVT) who were started on anticoagulation and those who had an indication for long-term anticoagulation at the time of SSPE diagnosis (e.g. atrial fibrillation). The primary outcome was recurrent VTE events other than SSPE, occurring after the diagnosis among patients managed without anticoagulation, and after treatment initiation among those treated with anticoagulation.

Results: Overall, 120 patients with a diagnosis of acute SSPE were included in the analysis. The mean age of the participants was 59 +/- 3 years, 47% were women, the mean body weight was 76 +/- 4 kg, and 35% of them had active cancer. Seventy-nine patients (66%) were treated with anticoagulation, whereas 41 patients (34%) were not. The most frequent treatment was direct oral anticoagulant, being used in 64/79 patients (81%), whereas 15/79 patients (19%) received low molecular weight heparin. Most patients were treated for 3-6 months. Twenty-one (28%) of treated patients continued long-term anticoagulation for secondary prevention. Individuals with active cancer at time of SSPE diagnosis were 32/79 (41%) and 10/41 (24%), respectively among treated and not treated patients. Overall, duration of follow-up was 452 +/- 77 days; 7 patients were lost to follow-up. Recurrent VTE events occurred in 7/113 (6.2%) patients: 5/75 (6.7%, 95% CI 2.2 to 14.9) of them were diagnosed in the treatment group (2 occurred while on anticoagulation and 3 after discontinuation of treatment) and the other 2/38 (5.3%, 95% CI 0.6 to 17.8) were detected among patients managed without anticoagulation. Recurrences were mostly represented by more proximal PEs (5 patients), one patient had an upper extremity DVT and the other one was diagnosed with both DVT and proximal PE.

Conclusions: In our retrospective cohort study, most patients diagnosed with an acute SSPE received anticoagulation. The prevalence of recurrent thromboembolic events detected over more than a year follow-up was relatively high, with 6.7% and 5.3%, respectively, among patients treated with anticoagulation and those managed without anticoagulation. Further data are needed to better understand the natural history of this thrombotic complication and to identify the right patients who would benefit from anticoagulation.

Carrier:Servier: Honoraria; BMS-Pfizer: Honoraria, Research Funding; Leo Pharma: Honoraria, Research Funding; Bayer: Honoraria; Sanofi: Honoraria. Le Gal:Sanofi: Membership on an entity's Board of Directors or advisory committees, Other: Lectures; Pfizer: Membership on an entity's Board of Directors or advisory committees, Other: Lectures; Stago: Other: Lectures; BMS: Other: Lectures; LEO Pharma: Other: Lectures; Inari: Membership on an entity's Board of Directors or advisory committees.

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