Risk Stratification of Acute Pulmonary Embolism: Outcomes in Patients With Intermediate sPESI Scores and Negative Cardiac Biomarkers

Background Current pulmonary embolism (PE) guidelines support outpatient management for selected low‐risk patients, typically identified using the simplified Pulmonary Embolism Severity Index (sPESI). The prognostic value of individual sPESI scores in the direct oral anticoagulant (DOAC) era, particularly when combined with cardiac biomarker assessment, remains uncertain. Research Question To evaluate 7‐day and 30‐day all‐cause mortality among patients with acute PE, sPESI scores of 2 or 3, and negative cardiac biomarkers treated with a DOAC. Study Design and Methods Retrospective cohort study of US adults diagnosed with acute PE in a VA emergency department and prescribed a DOAC within 24 h of diagnosis at any U.S. Veterans Affairs (VA) Health System from 2015 to 2024. Main Outcome Measures Seven‐day and 30‐day all‐cause mortality. Results Of 6427 eligible patients, 1365 had an sPESI score of 2 and 455 had an sPESI score of 3 with negative cardiac biomarkers. In the sPESI 2 cohort, 7‐day and 30‐day mortality were 0.44% and 1.39%, respectively. In the sPESI 3 cohort, rates were 0.22% and 2.20%. Approximately 71% of sPESI 2 patients and 75% of sPESI 3 patients were hospitalized. Hospitalization was not associated with lower 7‐day or 30‐day mortality in either cohort. Interpretation Patients with acute PE, sPESI scores of 2 or 3, and negative cardiac biomarkers had low short‐term mortality in this large, contemporary DOAC‐treated cohort. These findings support prospective studies evaluating outpatient management in carefully selected patients.