Effect of a Diagnostic Strategy Using an Elevated and Age-Adjusted D-Dimer Threshold on Thromboembolic Events in Emergency Department Patients With Suspected Pulmonary Embolism

Abstract

IMPORTANCE Uncontrolled studies suggest that pulmonary embolism (PE) can be safely ruled out using the YEARS rule, a diagnostic strategy that uses varying D-dimer thresholds.OBJECTIVE To prospectively validate the safety of a strategy that combines the YEARS rule with the pulmonary embolism rule-out criteria (PERC) rule and an age-adjusted D-dimer threshold. DESIGN, SETTINGS, AND PARTICIPANTSA cluster-randomized, crossover, noninferiority trial in 18 emergency departments (EDs) in France and Spain. Patients (N = 1414) who had a low clinical risk of PE not excluded by the PERC rule or a subjective clinical intermediate risk of PE were included from October 2019 to June 2020, and followed up until October 2020.INTERVENTIONS Each center was randomized for the sequence of intervention periods. In the intervention period (726 patients), PE was excluded without chest imaging in patients with no YEARS criteria and a D-dimer level less than 1000 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 × 10 in patients Ն50 years). In the control period (688 patients), PE was excluded without chest imaging if the D-dimer level was less than the age-adjusted threshold. MAIN OUTCOMES AND MEASURESThe primary end point was venous thromboembolism (VTE) at 3 months. The noninferiority margin was set at 1.35%. There were 8 secondary end points, including chest imaging, ED length of stay, hospital admission, nonindicated anticoagulation treatment, all-cause death, and all-cause readmission at 3 months. RESULTSOf the 1414 included patients (mean age, 55 years; 58% female), 1217 (86%) were analyzed in the per-protocol analysis. PE was diagnosed in the ED in 100 patients (7.1%). At 3 months, VTE was diagnosed in 1 patient in the intervention group (0.15% [95% CI, 0.0% to 0.86%]) vs 5 patients in the control group (0.80% [95% CI, 0.26% to 1.86%]) (adjusted difference, −0.64% [1-sided 97.5% CI, −ϱ to 0.21%], within the noninferiority margin). Of the 6 analyzed secondary end points, only 2 showed a statistically significant difference in the intervention group compared with the control group: 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]).CONCLUSIONS AND RELEVANCE Among ED patients with suspected PE, the use of the YEARS rule combined with the age-adjusted D-dimer threshold in PERC-positive patients, compared with a conventional diagnostic strategy, did not result in an inferior rate of thromboembolic events.

Current use of D-dimer for the exclusion of venous thrombosis in hospitalized patients

“…Since this is a real-life observational retrospective study, we used clinically relevant VTE as primary endpoint in the evaluation of the D-dimer assay, this method was implemented and validated by others 25 , 26 . In a non-inferiority study on emergency visitors’ population Freund et al 45 showed that even when positive AADD is encountered up to 1000 ng/dL patients could be excluded from further evaluation, these findings are consistent with our results.…”

D-Dimer Is Associated With Coronary Microvascular Dysfunction in Patients With Non-obstructive Coronary Artery Disease and Preserved Ejection Fraction

“…Second, we used the logistic regression models simultaneously for unadjusted, minimally adjusted, and fully adjusted analyses to evaluate the associations between D-dimer and CMVD. Considering the potential influence of age on D-dimer concentration, we added the sensitivity analyses to assess the relationship using an age-adjusted cut-off (500 ng/ml, if age is <50 years or age in years ×10 in patients ≥50 years) ( 18 , 19 ). Third, because D-dimer is a continuous variable, to visually assess the non-linear relationship between D-dimer level and risk of CMVD, a restricted cubic spline curve was used.…”

Just the facts: testing patients with suspected pulmonary embolism

“…When there are one or more YEARS items, use a d -dimer threshold of 500 ng/ml. One European study has externally validated a form of the YEARS score, (modified with age-adjust d -dimer in the patients with no YEARS items), where 1/648 patients negative for PE were diagnosed with venous thrombosis over the following 3 months [ 11 ]. Some d -dimer assays (such as the HemosIL d -dimer) have a different recommended cutoff and have never been studied use with the YEARS score (Table 2 ).…”