Subsegmental Pulmonary Embolism: To Treat or Not to Treat?

There has long been controversy on whether patients with isolated subsegmental pulmonary embolism (SSPE) should be treated with anticoagulation therapy. This stems in part from a lack of randomized trial evidence in this patient population.¹  Additionally, while the introduction of modern multidetector CT pulmonary angiography has led to an increase in PE diagnosis (including SSPE), there has been no increase in overall PE-related mortality and an overall decrease in PE-related case fatality, suggesting a lower disease severity compared with more proximal PE.²  The 2021 American College of Chest Physicians venous thromboembolism (VTE) guideline update suggested that SSPE management should depend on whether there is a low risk (clinical surveillance suggested) or high risk (anticoagulation suggested) of VTE recurrence.³ 

In this multicenter prospective cohort study, Dr. Grégoire Le Gal and colleagues sought to ascertain the recurrence risk for patients with untreated isolated SSPE. They included patients with single or multiple SSPE who had no proximal deep vein thrombosis (DVT) on bilateral leg ultrasounds done at the time of diagnosis, and five to seven days later. If proximal DVT was confirmed on initial or repeat ultrasound, then patients received anticoagulation therapy. Otherwise, these patients did not receive anticoagulation and received follow-up for 90 days. The researchers excluded certain high-risk patient groups — those with active cancer, prior VTE, baseline hypoxemia, and pregnancy, as well as hospitalized patients. The primary outcome was symptomatic recurrent VTE during 90-day follow-up (new proximal DVT or PE).

Among 292 patients with isolated SSPE, 28 had DVT (6 proximal and 22 distal) on initial or repeated bilateral leg ultrasounds; 20 of these patients initiated anticoagulation therapy. Two-hundred sixty-six patients were treated without anticoagulation. The primary outcome occurred in 3.1 percent (95% CI, 1.6-6.1%) over 90 days of follow-up; recurrent VTE events included four PE (1.4%) and four proximal DVT (1.5%), and there were no fatal recurrences. Two (0.7%) of the 292 patients had a major bleeding event (1 fatal episode of hemoptysis), neither of whom were receiving anticoagulation therapy. Though few in number, the following characteristics were associated with a higher rate of recurrence: multiple isolated SSPE (compared with single SSPE; hazard ratio [HR], 2.7; 95% CI, 0.7-11.0) and age greater than 65 years (compared with age < 65 years; HR, 3.2; 95% CI, 0.8-13.5).

There were a few limitations with this study. The authors did not report on whether initial SSPE events were provoked or unprovoked, or whether hormonal therapy was present or absent, which could impact recurrence risk. The study also took 10 years to reach its recruitment target, which may affect its generalizability. There was also no central adjudication of outcomes, and the diagnosis of SSPE is known to be subject to interobserver variability.⁴ 

We can draw several conclusions from these data, which represent the first large prospective study on the natural history of untreated isolated SSPE. First, the recurrence rate of 3.1 percent within 90 days was higher than expected and may be closer to the recurrence rate for more proximal PE.⁵  This surprisingly high recurrence rate in a lower risk population (without active cancer, pregnancy, or prior VTE) suggests that such patients may be at higher risk of recurrent VTE than initially suspected when anticoagulation is forgone. This study is also hypothesis-generating in suggesting that there may be subgroups that are at higher risk of recurrence — those with multiple SSPE or who are older than 65 years. Finally, the management algorithm in this study involved the use of surveillance leg ultrasound five to seven days after initial diagnosis, which in some cases did yield additional cases of DVT that led to the initiation of anticoagulation therapy. Thus, I would argue that patients with isolated SSPE who are managed without anticoagulation should have follow-up leg ultrasounds one week after initial diagnosis.