Yonathan Freund1,2, Anthony Chauvin3, Sonia Jimenez4, Anne-Laure Philippon1,2, Sonja Curac5, Florent Fémy6,7, Judith Gorlicki8, Tahar Chouihed9, Hélène Goulet10, Emmanuel Montassier11, Margaux Dumont2, Laura Lozano Polo12, Pierrick Le Borgne13, Mehdi Khellaf14, Donia Bouzid15,16, Pierre-Alexis Raynal17, Nizar Abdessaied18, Saïd Laribi19, Jeremy Guenezan20, Olivier Ganansia21, Ben Bloom22, Oscar Miró3, Marine Cachanado23, Tabassome Simon1,23. 1. Sorbonne Université, Improving Emergency Care FHU, Paris, France. 2. Emergency Department, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France. 3. Emergency Department, Hôpital Lariboisière, Assistance Publique-Hôpitaux de Paris, Paris, France. 4. Emergency Department, Hospital Clínic, IDIBAPS, Barcelona, University of Barcelona, Catalonia, Spain. 5. Emergency Department, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Clichy, France. 6. Emergency Department, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Paris University, Paris, France. 7. Toxicology and Chemical Risks Department, French Armed Forces Biomedical Institute, Bretigny-Sur-Orges, France. 8. Emergency Department, Hôpital Avicenne, Assistance Publique-Hôpitaux de Paris, INSERM U942-MASCOT, Bobigny, France. 9. Emergency Department, University Hospital of Nancy, Université de Lorraine, UMR_S 1116, Nancy, France. 10. Emergency Department, Hôpital Tenon, Assistance Publique-Hôpitaux de Paris, Paris, France. 11. Emergency Department, CHU Nantes, Nantes, France. 12. Emergency Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Universitat Autònoma de Barcelona, Catalonia, Spain. 13. Emergency Department, Hôpitaux Universitaires de Strasbourg, Strasbourg, France. 14. Emergency Department, CHU Henri Mondor, INSERM U955, Assistance Publique-Hôpitaux de Paris, Paris, France. 15. Université de Paris, INSERM, IAME, F-75006 Paris, France. 16. Emergency Department, Bichat-Claude Bernard University Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France. 17. Emergency Department, Hôpital St-Antoine, Assistance Publique-Hôpitaux de Paris, Paris, France. 18. Emergency Department, Centre Hospitalier de St Denis, St Denis, France. 19. Tours University, Emergency Medicine Department, Tours University Hospital, Tours, France. 20. Emergency Department, University Hospital of Poitiers, Poitiers, France. 21. Emergency Department, Groupe Hospitalier Paris-St Joseph, Paris, France. 22. Emergency Department, Barts Health NHS Trust, London, United Kingdom. 23. Department of Clinical Pharmacology and Clinical Research Platform Paris-East (URCEST-CRC-CRB), Assistance Publique-Hôpitaux de Paris, Sorbonne University, St Antoine Hospital, Paris, France.
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 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. 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 ≥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. Results: 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. Trial Registration: ClinicalTrials.gov Identifier: NCT04032769.
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 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. 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 ≥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. Results: 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. Trial Registration: ClinicalTrials.gov Identifier: NCT04032769.
Authors: C E A Dronkers; T van der Hulle; G Le Gal; P A Kyrle; M V Huisman; S C Cannegieter; F A Klok Journal: J Thromb Haemost Date: 2017-03-11 Impact factor: 5.824
Authors: Clive Kearon; Kerstin de Wit; Sameer Parpia; Sam Schulman; Marc Afilalo; Andrew Hirsch; Frederick A Spencer; Sangita Sharma; Frédérick D'Aragon; Jean-François Deshaies; Gregoire Le Gal; Alejandro Lazo-Langner; Cynthia Wu; Lisa Rudd-Scott; Shannon M Bates; Jim A Julian Journal: N Engl J Med Date: 2019-11-28 Impact factor: 91.245
Authors: L M van der Pol; C E A Dronkers; T van der Hulle; P L den Exter; C Tromeur; C Heringhaus; A T A Mairuhu; M V Huisman; W B van den Hout; F A Klok Journal: J Thromb Haemost Date: 2018-03-13 Impact factor: 5.824
Authors: Andrea Penaloza; Caroline Soulié; Thomas Moumneh; Quentin Delmez; Alexandre Ghuysen; Dominique El Kouri; Christian Brice; Nicolas S Marjanovic; Jacques Bouget; Fares Moustafa; Albert Trinh-Duc; Catherine Le Gall; Lionel Imsaad; Jean-Marie Chrétien; Béatrice Gable; Philippe Girard; Olivier Sanchez; Jeannot Schmidt; Grégoire Le Gal; Guy Meyer; Nicolas Delvau; Pierre-Marie Roy Journal: Lancet Haematol Date: 2017-11-14 Impact factor: 18.959