Among emergency department patients with suspicion of pulmonary embolism (PE) not ruled out by the pulmonary embolism rule-out criteria (PERC) rule, does use of a diagnostic strategy that combines the YEARS rule and age-adjusted D-dimer threshold safely exclude the diagnosis of venous thromboembolism?
In this cluster-randomized, crossover, noninferiority trial that included 1414 patients with a suspicion of PE in France and Spain, the 3-month risk of a missed thromboembolic event using the intervention diagnostic strategy, compared with a conventional strategy, was 0.15% vs 0.80%; the confidence interval of this difference did not cross the noninferiority margin of 1.35%.
Among emergency department patients with suspected PE who were PERC positive, the use of the YEARS rule combined with the age-adjusted D-dimer threshold did not lead to an inferior rate of thromboembolic events compared with a conventional diagnostic strategy.
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.
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 Participants
A 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.
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 ≥50 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 Measures
The 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.
Of 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, −∞ 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.
ClinicalTrials.gov Identifier: NCT04032769
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CME Disclosure Statement: Unless noted, all individuals in control of content reported no relevant financial relationships. If applicable, all relevant financial relationships have been mitigated.
Corresponding Author: Yonathan Freund, MD, PhD, Service d’Accueil des Urgences, 47-83 Bd de l’Hôpital, 75013 Paris, France (email@example.com).
Accepted for Publication: November 1, 2021.
Author Contributions: Drs Freund and Simon had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Freund, Philippon, Raynal, Ganansia, Bloom, Cachanado, Simon.
Acquisition, analysis, or interpretation of data: Freund, Chauvin, Jimenez, Philippon, Curac, Fémy, Gorlicki, Chouihed, Goulet, Montassier, Dumont, Lozano Polo, Le Borgne, Khellaf, Bouzid, Raynal, Abdessaied, Laribi, Guenezan, Miró, Bloom, Cachanado.
Drafting of the manuscript: Freund, Raynal, Bloom, Cachanado.
Critical revision of the manuscript for important intellectual content: Freund, Chauvin, Jimenez, Philippon, Curac, Fémy, Gorlicki, Chouihed, Goulet, Montassier, Dumont, Lozano Polo, Le Borgne, Khellaf, Bouzid, Raynal, Abdessaied, Laribi, Guenezan, Ganansia, Miró, Bloom, Simon.
Statistical analysis: Abdessaied, Cachanado.
Obtained funding: Freund, Philippon, Cachanado, Simon.
Administrative, technical, or material support: Philippon, Raynal, Laribi, Miró, Simon.
Supervision: Freund, Philippon, Ganansia, Simon.
Conflict of Interest Disclosures: Dr Laribi reported receiving personal fees from Novartis, Bristol Myers Squibb, Aspen, and AstraZeneca outside the submitted work. Dr Miró reported receiving grants from ISCIII_Spanish Ministry of Health (FIS18/00393) outside the submitted work. Dr Simon reported receiving grants from the French Ministry of Health, AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi-Sankyo, Eli Lilly, GlaxoSmithKline, Novartis, and Sanofi; personal fees from AstraZeneca, Ablative Solutions, Bayer, Novartis, Sanofi, and 4Living Biotech; and fees for conferences, counseling, and/or research grants from Merck Sharp & Dohme, Amgen, and Sanofi outside the submitted work. No other disclosures were reported.
Funding/Support: This research was funded by a grant from the French Health Ministry (Programme Hospitalier de Recherche Clinique 2017). The sponsor was the Assistance Publique–Hôpitaux de Paris.
Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Data Sharing Statement: See Supplement 4.
Additional Contributions: We thank Pierre Hausfater, MD, PhD (Assistance Publique–Hôpitaux de Paris, France), for his help and support. Dr Hausfater did not receive any compensation for his role in this study.
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