Outpatient Treatment of Low-risk Pulmonary Embolism in the Era of Direct Oral Anticoagulants: A Systematic Review

Background: Clinical guidelines have supported outpatient treatment of low-risk pulmonary embolism (PE) since 2014, but adoption of this practice has been slow. Direct oral anticoagulant (DOAC) therapy for venous thromboembolism (VTE) is now as common as vitamin K antagonist treatment, but data are sparse regarding outcomes for patients with low-risk PE treated with DOACs as outpatients. We conducted a systematic review of literature on outcomes of outpatient management for PE, including comparisons to inpatient treatment and differences by anticoagulant class. Methods: We searched Medline, Embase, PubMed, CENTRAL, clinicaltrials.gov, and ICTRN for studies published from January 1980 through February 2019 using a predefined strategy developed with a medical librarian. We included English-language randomized controlled trials (RCTs) and prospective nonrandomized trials (NRTs) of adult patients diagnosed with acute, symptomatic PE, and discharged from the emergency department or within 48 hours. Our primary outcome included four major adverse outcomes (all-cause mortality, PE-related mortality, recurrent VTE, and major bleeding) within 30 and 90 days. A preplanned subanalysis of high-quality studies assessed outcomes associated with different anticoagulation treatment classes. Results: Our initial search identified 6,818 records, of which 12 studies (four RCT, eight NRT) with a total of 3,191 patients were included in the review. All RCTs and six NRTs were determined to have low to moderate risk of bias and were classified as high quality. Outpatients in these studies (n = 1,814) had rates of 90-day major adverse outcomes below 1%, including all-cause mortality (0.7%, 95% confidence interval [CI] = 0.4% to 1.2%), PE-related mortality (0.06%, 95% CI = 0.01% to 0.3%), recurrent VTE (0.8%, 95% CI = 0.5% to 1.4%), and major bleeding (0.8%, 95% CI = 0.5% to 1.4%). Exploratory analysis revealed no association between anticoagulant treatment class and rates of major adverse outcomes. Conclusion: Among patients with low-risk PE treated as outpatients, few patients experienced major adverse outcomes such as mortality, recurrent VTE, or major bleeding within 90 days.