The use of a diagnostic strategy with age-adjusted D-dimer thresholds was non-inferior in risk-stratifying for thromboembolic events in emergency department patients with suspected pulmonary embolism

1. Compared to conventional diagnostic strategy, the use of the YEARS rule combined with the age-adjusted D-dimer threshold did not result in an inferior rate of thromboembolic events in patients with suspected pulmonary embolism in the emergency department.

2. The use of YEARS criteria in combination with the PERC criteria significantly decreased the use of chest imaging in this patient population, emphasizing the value of combining the 2 criteria sets with clinical assessment.

Evidence Rating Level: 1 (Excellent)

Study Rundown: The assessment algorithm and optimal diagnostic strategy to rule out suspected pulmonary embolism (PE) in patients varies across centers and is a much-debated subject. The YEARS rules and PERC rules combined with age-adjusted D dimer thresholds are diagnostic criteria strategies that use varying D-dimer thresholds to help safely rule out PE and have been validated in separate studies. However, their combination use has not been investigated in a randomized trial. This noninferiority trial assessed whether a strategy combining the YEARS rule with the age-adjusted D-dimer cutoff component of the PERC rule could help safely rule out the diagnosis of PE in suspected patients in the emergency department (ED). The primary endpoint was venous thromboembolism (VTE) at 3 months where the noninferiority margin was set at 1.35%. Secondary endpoints included chest imaging, ED length of stay, hospital admission, nonindicated anticoagulation treatment, all-cause death, and all-cause readmission at 3 months. Among 1,414 patients with clinically suspected PE, the 3-month risk of a missed VTE event using the intervention diagnostic strategy vs conventional strategy was 0.15% vs 0.80%, below the noninferiority margin. These results suggested that compared to conventional diagnostic strategy, the use of the YEARS rule combined with the age-adjusted D-dimer threshold in PERC-positive patients did not result in an inferior rate of VTE events in ED patients with suspected PE. A limitation of this study was that the 2 patient groups may have had confounding, clinically relevant differences that occurred because of the center-level randomization, as opposed to patient-level.

Click to read the study in JAMA

Click to read an accompanying editorial in JAMA

Relevant Reading: Modified diagnostic strategy to safely rule-out pulmonary embolism in the emergency department: study protocol for the non-inferiority MODIGLIANI cluster cross-over randomized trial

In-Depth [randomized clinical trial]: This cluster-randomized, crossover, noninferiority trial included 1,414 patients (mean age, 55 years; 58% female) from 18 EDs in France and Spain between October 2019 to June 2020. Inclusion criteria included patients with a low clinical risk of PE not excluded by the PERC rule or a subjective clinical intermediate risk of PE. In the randomized intervention period (N = 726), PE was excluded without chest imaging in patients with no YEARS criteria and a D-dimer level less than 1,000 ng/mL and in patients with 1 or more YEARS criteria and a D-dimer level less than the age-adjusted threshold (500 ng/mL if age <50 years or age in years x 10 in patients ≥50 years). In the control period (N = 688), PE was excluded without chest imaging if the D-dimer level was less than the age-adjusted threshold. In total, PE was diagnosed in 100 patients (7.1%) where VTE was subsequently diagnosed at 3 months in 1 patient in the intervention group (0.15% [95%CI, 0.0%to 0.86%]) compared to 5 patients in the control group (0.80% [95%CI, 0.26% to 1.86%]) (adjusted difference, −0.64% [1-sided 97.5%CI, −∞ to 0.21%], within the noninferiority margin). Among secondary endpoints, only 2 showed a statistically significant difference between the intervention vs control groups: chest imaging (30.4% vs 40.0%; adjusted difference, −8.7% [95%CI, −13.8% to −3.5%]) and ED median length of stay (6 hours [IQR, 4 to 8 hours] vs 6 hours [IQR, 5 to 9 hours]; adjusted difference, −1.6 hours [95%CI, −2.3 to −0.9]).

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