Long-Term Outcomes of Patients with Isolated Sub-Segmental Pulmonary Embolism Managed without Anticoagulant Therapy

Introduction:

The management of patients with isolated sub-segmental pulmonary embolism (SSPE) is controversial. The 2021 update of the American College of Chest physician clinical practice guidelines suggest withholding anticoagulant therapy in patients at low risk of recurrent venous thromboembolism (VTE) but to initiate anticoagulation in those at high risk of recurrent events. The SSPE prospective management cohort study, which included patients with SSPE at low risk of VTE managed without anticoagulant therapy, reported a 3-month risk of recurrent events of approximately 3%. However, the long-term risk of recurrent VTE (i.e., beyond the initial 3 months) is unknown. We sought to establish the long-term incidence rates of recurrent VTE and clinically relevant bleeding complications in this patient population.

Methods:

We performed a retrospective cohort study of patients included in the SSPE prospective management cohort study included at The Ottawa Hospital between 2011 and 2021. The primary outcome of the study was a major recurrent VTE occurring beyond the initial three months of follow-up. Major VTE was defined as recurrent proximal deep vein thrombosis (DVT) or pulmonary embolism (PE) (segmental or more proximal). Secondary outcomes included any recurrent VTE (including SSPE and distal DVT) and clinically relevant bleeding (combining major and clinically relevant non-major bleeding (CRNMB)) occurring beyond the initial three months of follow-up. Major bleeding and CRNMB were defined as per the International Society on Thrombosis and Haemostasis. Patients were censored at the time of the event, death, last known encounter or the end of the follow-up period (April 2024). Incidence rates along with their 95% confidence intervals (CI) for the primary and secondary outcome measures were computed by performing time-to-event analyses using the Kaplan-Meier method. Analyses were performed using SPSS 29.0 (IBM Corp.).

Results:

A total of 138 patients with isolated SSPE were included in the analysis. Mean age was 52.3 ± 16.6 years and 50.7% were female. The mean duration of follow-up was 6.0 years (range 0 to 13 years). Overall, recurrent major VTE occurred in 15 out of the 138 patients leading to an incidence rate of 1.93 per 100 patient-years (95% CI: 1.17-3.16). Among these, 9 patients experienced a recurrent PE (segmental or more proximal), 4 had a proximal DVT (3 lower extremity and 1 upper extremity), and 2 had both PE and DVT. Any VTE were observed in 23 out of the 138 patients, resulting in an incidence rate of 3.09 per 100 patient-years (95% CI: 2.07-4.59). Despite not being managed with anticoagulant therapy, clinically relevant bleeding was reported in 15 patients during the follow-up period, corresponding to a cumulative incidence rate of 1.88 per 100 patient-years (95% CI: 1.14-3.08). Of these, 12 patients experienced clinically relevant non-major bleeding, while 3 patients experienced major bleeding.

Conclusion:

The long-term incidence of VTE is relatively low in patients with isolated SSPE managed without anticoagulation, yet higher than that observed in the general population. The incidence rates of clinically relevant bleeding without anticoagulation is not negligeable. Future studies are needed to assess the risk benefit ratio of anticoagulation in this patient population.

Carrier:Bayer: Honoraria; Anthos: Honoraria; Pfizer: Honoraria, Research Funding; Leo Pharma: Honoraria, Research Funding; Sanofi: Honoraria; Regeneron: Honoraria; BMS: Honoraria, Research Funding; Servier: Honoraria. Shaw:Diagnostica Stago: Other: in-kind laboratory support. Le Gal:Pfizer, Sanofi, Aspen Pharma: Honoraria; BMS-Pfizer: Research Funding.