Outpatient pulmonary embolism treatment not inferior to inpatient management, study finds

Outpatient care for pulmonary embolism (PE) can safely and effectively be used in place of inpatient care in patients with low risk of death, according to a new study.

Researchers conducted an open-label, randomized, non-inferiority trial at 19 emergency departments in Switzerland, France, Belgium and the U.S., between February 2007 and June 2010. Subjects were 18 years of age or older with acute, symptomatic and objectively verified PE and a low death risk, defined as a risk class of I or II on the pulmonary embolism severity index. This index is a clinical prognostic model that assigns risk according to an overall point score obtained by adding the patient's age in years to points assigned to other applicable predictors (male sex, history of or active cancer, heart failure, chronic lung disease, pulse ≥110 beats/min, systolic blood pressure <100 mm Hg, respiratory rate ≥30 breaths/min, temperature below 36 degrees Celsius, altered mental status, and arterial oxygen saturation <90%). Higher scores indicate a higher risk class.

Researchers defined PE as the acute onset of dyspnea or chest pain, together with a new contrast filling defect on spiral computed tomography or pulmonary angiography, a new high-probability ventilation-perfusion lung scan, or documentation of a new proximal deep vein thrombosis either by venous ultrasonography or contrast venography. Patients with at least one of the following characteristics were excluded: arterial hypoxemia, systolic blood pressure below 100 mm Hg, chest pain requiring parenteral opioids, active bleeding, high risk of bleeding (stroke during the preceding 10 days, gastrointestinal bleeding during the preceding 14 days or <75,000 platelets per mm³), severe renal failure (creatinine clearance <30 mL/min according to the Cockcroft-Gault equation), extreme obesity (body mass >150 kg), history of heparin-induced thrombocytopenia or allergy to heparins, therapeutic oral anticoagulation at the time of PE diagnosis, any barriers to treatment adherence or follow-up (e.g., current alcohol abuse or illicit drug use), pregnancy, imprisonment, diagnosis of PE more than 23 hours before screening, or previous enrollment in the trial.

In the study, 344 consecutive adults were randomized to initial outpatient (discharged from the hospital <24 hours after randomization) or inpatient treatment with subcutaneous enoxaparin (≥5 days) followed by oral anticoagulation (≥90 days). The primary outcome was symptomatic, recurrent venous thromboembolism (VTE) within 90 days. Safety outcomes included major bleeding within 14 or 90 days and mortality within 90 days. Results appeared in the July 2 The Lancet.

In the primary analysis, one of 171 outpatients, a woman with cervical cancer who initially had bilateral segmental PE, developed recurrent VTE within 90 days, compared with none of 168 inpatients (95% upper confidence limit [UCL], 2.7%; P=0.011). Researchers pointed out that this UCL suggests that the true outpatient event rate is not likely to exceed the true inpatient event rate by more than 2.7%.

One patient in each treatment group died within 90 days (95% UCL, 2.1%; P=0.005), and two of 171 outpatients and no inpatients had major bleeding within 14 days (95% UCL, 3.6%; P=0.031). By 90 days, three outpatients but no inpatients had developed major bleeding (95% UCL, 4.5%; P=0.086).

The major bleeds were intramuscular hematomas occurring on days 3 and 13 (one patient had insertion of a vena cava filter). One additional outpatient developed major bleeding within 90 days (menometrorrhagia on day 50).

Outpatients had a mean of 3.4 fewer days of initial hospital stay, with similar hospital readmission rates, emergency department visits, and outpatient visits to doctors to the inpatient group. Outpatients had 2.6 more days of treatment with low-molecular-weight heparin than inpatients.

Researchers wrote, “Although we showed non-inferiority for outpatient treatment with respect to major bleeding at 14 days, we did not achieve non-inferiority at 90 days because of an additional bleeding episode that occurred 50 days after randomization. However, given this time latency, it is unlikely that this bleeding event was related to randomization to outpatient treatment.”