Milou A M Stals1, Toshihiko Takada2, Noémie Kraaijpoel3, Nick van Es3, Harry R Büller3, D Mark Courtney4, Yonathan Freund5, Javier Galipienzo6, Grégoire Le Gal7, Waleed Ghanima8, Menno V Huisman1, Jeffrey A Kline9, Karel G M Moons10, Sameer Parpia11, Arnaud Perrier12, Marc Righini12, Helia Robert-Ebadi12, Pierre-Marie Roy13, Maarten van Smeden10, Phil S Wells7, Kerstin de Wit14, Geert-Jan Geersing10, Frederikus A Klok1. 1. Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands (M.A.M.S., M.V.H., F.A.K.). 2. Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands, and Department of General Medicine, Shirakawa Satellite for Teaching and Research (STAR), Fukushima Medical University, Fukushima, Japan (T.T.). 3. Department of Vascular Medicine, Amsterdam University Medical Center, location AMC, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands (N.K., N.v.E., H.R.B.). 4. Department of Emergency Medicine, The University of Texas Southwestern Medical Center, Dallas, Texas (D.M.C.). 5. Department of Emergency Medicine, Pitié-Salpêtrière University Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France (Y.F.). 6. Service of Anesthesiology, Hospital MD Anderson Cancer Center, Madrid, Spain (J.G.). 7. Department of Medicine, University of Ottawa, Ottawa Hospital Research Institute, Thrombosis Research Group, Ottawa, Ontario, Canada (G.L.G., P.S.W.). 8. Department of Medicine, Østfold Hospital Trust and Institute of Clinical Medicine, University of Oslo, Oslo, Norway (W.G.). 9. Department of Emergency Medicine, Indiana University School of Medicine, Indianapolis, Indiana (J.A.K.). 10. Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands (K.G.M.M., M.v.S., G.J.G.). 11. Department of Oncology, McMaster University, Hamilton, Ontario, Canada (S.P.). 12. Division of Angiology and Hemostasis, Department of Medical Specialties, Geneva University Hospital and Faculty of Medicine, Geneva, Switzerland (A.P., M.R., H.R.E.). 13. Department of Emergency Medicine, University of Angers, Angers, France (P.M.R.). 14. Department of Emergency Medicine, Queen's University, Kingston, and Departments of Medicine and Health Research Methods, Evidence, and Impact (HEI), McMaster University, Hamilton, Ontario, Canada (K.d.W.).
Abstract
BACKGROUND: How diagnostic strategies for suspected pulmonary embolism (PE) perform in relevant patient subgroups defined by sex, age, cancer, and previous venous thromboembolism (VTE) is unknown. PURPOSE: To evaluate the safety and efficiency of the Wells and revised Geneva scores combined with fixed and adapted D-dimer thresholds, as well as the YEARS algorithm, for ruling out acute PE in these subgroups. DATA SOURCES: MEDLINE from 1 January 1995 until 1 January 2021. STUDY SELECTION: 16 studies assessing at least 1 diagnostic strategy. DATA EXTRACTION: Individual-patient data from 20 553 patients. DATA SYNTHESIS: Safety was defined as the diagnostic failure rate (the predicted 3-month VTE incidence after exclusion of PE without imaging at baseline). Efficiency was defined as the proportion of individuals classified by the strategy as "PE considered excluded" without imaging tests. Across all strategies, efficiency was highest in patients younger than 40 years (47% to 68%) and lowest in patients aged 80 years or older (6.0% to 23%) or patients with cancer (9.6% to 26%). However, efficiency improved considerably in these subgroups when pretest probability-dependent D-dimer thresholds were applied. Predicted failure rates were highest for strategies with adapted D-dimer thresholds, with failure rates varying between 2% and 4% in the predefined patient subgroups. LIMITATIONS: Between-study differences in scoring predictor items and D-dimer assays, as well as the presence of differential verification bias, in particular for classifying fatal events and subsegmental PE cases, all of which may have led to an overestimation of the predicted failure rates of adapted D-dimer thresholds. CONCLUSION: Overall, all strategies showed acceptable safety, with pretest probability-dependent D-dimer thresholds having not only the highest efficiency but also the highest predicted failure rate. From an efficiency perspective, this individual-patient data meta-analysis supports application of adapted D-dimer thresholds. PRIMARY FUNDING SOURCE: Dutch Research Council. (PROSPERO: CRD42018089366).
BACKGROUND: How diagnostic strategies for suspected pulmonary embolism (PE) perform in relevant patient subgroups defined by sex, age, cancer, and previous venous thromboembolism (VTE) is unknown. PURPOSE: To evaluate the safety and efficiency of the Wells and revised Geneva scores combined with fixed and adapted D-dimer thresholds, as well as the YEARS algorithm, for ruling out acute PE in these subgroups. DATA SOURCES: MEDLINE from 1 January 1995 until 1 January 2021. STUDY SELECTION: 16 studies assessing at least 1 diagnostic strategy. DATA EXTRACTION: Individual-patient data from 20 553 patients. DATA SYNTHESIS: Safety was defined as the diagnostic failure rate (the predicted 3-month VTE incidence after exclusion of PE without imaging at baseline). Efficiency was defined as the proportion of individuals classified by the strategy as "PE considered excluded" without imaging tests. Across all strategies, efficiency was highest in patients younger than 40 years (47% to 68%) and lowest in patients aged 80 years or older (6.0% to 23%) or patients with cancer (9.6% to 26%). However, efficiency improved considerably in these subgroups when pretest probability-dependent D-dimer thresholds were applied. Predicted failure rates were highest for strategies with adapted D-dimer thresholds, with failure rates varying between 2% and 4% in the predefined patient subgroups. LIMITATIONS: Between-study differences in scoring predictor items and D-dimer assays, as well as the presence of differential verification bias, in particular for classifying fatal events and subsegmental PE cases, all of which may have led to an overestimation of the predicted failure rates of adapted D-dimer thresholds. CONCLUSION: Overall, all strategies showed acceptable safety, with pretest probability-dependent D-dimer thresholds having not only the highest efficiency but also the highest predicted failure rate. From an efficiency perspective, this individual-patient data meta-analysis supports application of adapted D-dimer thresholds. PRIMARY FUNDING SOURCE: Dutch Research Council. (PROSPERO: CRD42018089366).