D-Dimer thresholds for diagnosis of pulmonary embolism based on a single question: is it the most likely diagnosis? A prospective, multicentre, open-label, single-arm interventional study.

Abstract

Validated diagnostic strategies for pulmonary embolism allow raising the D-dimer threshold to 1000 ng/mL in selected patients with a low probability of pulmonary embolism, but adherence to this strategy in routine practice remains poor. Retrospective studies suggest that these rules could be replaced by a single clinical question as to whether pulmonary embolism is the most likely diagnosis. We aimed to assess the safety of a simplified approach that applies a 1000 ng/mL threshold when pulmonary embolism is unlikely and an age-adjusted threshold otherwise, including patients at a high probability for pulmonary embolism. In this prospective interventional study in 13 French hospital emergency departments, patients aged ≥18 years with a clinical suspicion of pulmonary embolism, who were not on full-dose anticoagulant therapy and had not had a thromboembolic event in the past 6 months, were included. The intervention consisted of ruling out pulmonary embolism without chest imaging in patients for whom pulmonary embolism was not considered the most likely diagnosis and had a D-dimer value <1000 ng/mL. The age-adjusted D-dimer threshold (500 ng/mL if aged <50 years or age × 10 ng/mL if aged ≥50 years) was used for the other patients. The primary outcome was the diagnostic failure rate (ie, occurrence of a thromboembolic event at 3 months of follow-up) among patients for whom pulmonary embolism was initially ruled out. Safety was established if the upper bound of the two-sided 95% CI for the diagnostic failure rate was less than 1·85% in patients for whom pulmonary embolism was ruled out at initial testing and in a subgroup of patients for whom it was ruled out without chest imaging. This study is registered with ClinicalTrials.gov (NCT06190392) and is complete. Between Jan 16 and Sept 5, 2024, 1365 patients were screened for eligibility and 1221 were included, of whom 80 (7%) were diagnosed with pulmonary embolism at initial testing. Pulmonary embolism was not considered the most likely diagnosis for 997 patients. The diagnostic failure rate was 0·00% (95% CI 0·00-0·34) and was 0·12% (0·01-0·55) after multiple imputation for 33 patients with no available follow-up, both within the safety threshold. In the prespecified subgroup of 796 patients for whom pulmonary embolism was ruled out without chest imaging, the diagnostic failure rate was 0·00% (0·00-0·46), also within the safety threshold. The strategy had a 32% chest imaging rate (384 of 1217 patients), an absolute reduction of 19% (16-21) compared with the fixed 500 ng/mL D-dimer threshold strategy (609 [50%] of 1215). There were 16 deaths during the 3-month follow-up. A global simplified strategy using a D-dimer threshold of 1000 ng/mL in patients for whom pulmonary embolism was not the most likely diagnosis, and an age-adjusted threshold for other patients, safely excluded the diagnosis. These findings indicate that this simplified strategy could safely reduce the use of chest imaging in the emergency department. Assistance Publique-Hôpitaux de Paris (Délégation à la Recherche Clinique et à l'Innovation).