Risk for recurrent venous thromboembolism in patients with subsegmental pulmonary embolism managed without anticoagulation : a multicenter prospective cohort study
Le Gal G, Kovacs MJ, Bertoletti L, et al. Ann Intern Med. 2022;175(1):29-35.
Many more pulmonary embolisms (PEs) have been diagnosed over the past 20 years, probably because of the advent of helical CTs. Simultaneously, the case fatality rate has substantially decreased, and the overall mortality rate has remained unchanged. This combination suggests overdiagnosis and overtreatment.
Several groups have argued that these small subsegmental, hemodynamically innocuous PEs diagnosed on chest CT are essentially normal variants and should not necessarily be treated with long-term anticoagulation.
The American College of Chest physicians practice guidelines actually suggest that clinical surveillance is appropriate for such cases (instead of anticoagulation) but indicate a low evidence rating for this recommendation. The authors of this study decided to rigorously follow those practice guidelines and report the incidence of subsequent venous thromboembolism (VTE).
This was a multicenter, international, prospective cohort study with no interventional component. It was performed in Switzerland, Holland, France, and Canada. Patients were enrolled if they had subsegmental PE (no proximal PE) and negative findings in bilateral venous duplex ultrasound of the lower extremities. Patients were excluded if they had active cancer or a known thrombophilia condition, were hospitalized before enrollment, or had an oxygen requirement. The enrolled patients did not receive anticoagulation.
The primary outcome was recurrent VTE, either deep vein thrombosis or PE, within 90 days. The secondary outcomes included death due to PE or bleeding events.
A priori, the authors estimated a risk of recurrent VTE in this population of 1% at 90 days. They calculated that 300 patients would be needed to demonstrate that this was the true recurrence rate with narrow CIs. For some reason, the authors took 10 years to enroll 292 patients (2011-2021).
The study protocol was somewhat unusual: the authors enrolled the patients, performed baseline ultrasounds, and then repeated the ultrasounds in 5 to 7 days to account for the possibility of calf deep vein thrombosis. Of the 292 patients, 28 had blood clots identified on either the initial or repeat ultrasound, thus leaving 262 patients managed without anticoagulation.
Of these 262 patients, 8 (3.1%, CI 1.6-6.1%) had recurrent VTE during the 90-day study period, and 4 died. None of these deaths were adjudicated to be due to recurrent VTE.
Among the 191 patients with isolated, single subsegment PEs who were <65 years of age, the incidence of recurrent VTE was 1.8%. The patients >65 years of age had a 5.5% rate of recurrent VTE.
The authors concluded that the VTE rate was definitely higher than those reported by several retrospective studies on this topic. The finding is nonetheless somewhat in line with the rate of recurrent VTE for patients with more proximal VTE who are treated with anticoagulation (3%).
The authors suggest that a subset of patients with very low risk of VTE might exist (eg, those <65 years of age) but could not be identified reliably in this study. Therefore, the best currently available evidence suggests that the average person with subsegmental PE should be treated, because the risks of treatment with anticoagulation are currently small. If a patient otherwise has a contraindication to anticoagulation, this article might be informative. Future studies will need to randomize patients to anticoagulation vs no anticoagulation to truly estimate the potential benefit of this treatment.
EDITOR’S COMMENTARY: This was a very important prospective cohort study of patients with subsegmental PE who were managed without anticoagulation. The 90-day incidence of recurrent VTE was 3.1%, a value significantly higher than anticipated by the authors. This finding generally suggests that most or all patients with such PEs should be treated with anticoagulants unless they have major contraindications.