Subscribe to RSS
Contemporary Management and Clinical Course of Acute Pulmonary Embolism: The COPE StudyFunding The study was supported by an unrestricted grant from Daiichi Sankyo Europe and Daiichi Sankyo Italy.
Background New diagnosis, risk stratification, and treatment strategies became recently available for patients with acute pulmonary embolism (PE) leading to changes in clinical practice and potentially influencing short-term patients' outcomes.
Research question The COntemporary management of PE (COPE) study is aimed at assessing the contemporary clinical management and outcomes in patients with acute symptomatic PE.
Study Design and Methods Prospective, noninterventional, multicenter study. The co-primary study outcomes, in-hospital and 30-day death, were reported overall and by risk categories according to the European Society of Cardiology (ESC) and American Heart Association guidelines.
Results Among 5,213 study patients, PE was confirmed by computed tomography in 96.3%. In-hospital, 289 patients underwent reperfusion (5.5%), 92.1% received parenteral anticoagulants; at discharge, 75.6% received direct oral anticoagulants and 6.7% vitamin K antagonists. In-hospital and 30-day mortalities were 3.4 and 4.8%, respectively. In-hospital death occurred in 20.3% high-risk patients (n = 177), in 4.0% intermediate-risk patients (n = 3,281), and in 0.5% low-risk patients (n = 1,702) according to ESC guidelines. Further stratification in intermediate-high and intermediate-low risk patients did not reach statistical significance, but intermediate-risk patients with sPESI > 0 alone had lower mortality compared to those with one or both among right ventricular dilation at echocardiography or increased troponin. Death or clinical deterioration occurred in 1.5, 5.0, and 9.4% of patients at low, intermediate-low, and intermediate-high risk for death according to ESC guidelines.
Conclusion For the majority of patients with PE, contemporary initial management includes risk stratification and treatment with direct oral anticoagulants. In-hospital mortality remains high in intermediate and high-risk patients calling for and informing research focused on its reduction.
Trial Registration number: NCT03631810.
C.B. and G.A. contributed substantially to study conception and design. C.B., D.L., A.P.M., M.M.G., and G.A. 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. D.L. contributed substantially to data analysis. All authors contributed to interpretation of the data, critical revision, and the writing of the manuscript.
* See Appendix (available in the online version) for the complete list of Centers and Investigators.
Prior abstract presentation : 2021 Congress of the American Society of Hematology.
Received: 17 May 2022
Accepted: 17 December 2022
Accepted Manuscript online:
09 February 2023
Article published online:
20 March 2023
© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
- 1 Barco S, Mahmoudpour SH, Valerio L. et al. Trends in mortality related to pulmonary embolism in the European Region, 2000-15: analysis of vital registration data from the WHO Mortality Database. Lancet Respir Med 2020; 8 (03) 277-287
- 2 Bikdeli B, Wang Y, Jimenez D. et al. Pulmonary embolism hospitalization, readmission, and mortality rates in US older adults, 1999-2015. JAMA 2019; 322 (06) 574-576
- 3 Jiménez D, de Miguel-Díez J, Guijarro R. et al; RIETE Investigators. Trends in the management and outcomes of acute pulmonary embolism: analysis from the RIETE registry. J Am Coll Cardiol 2016; 67 (02) 162-170
- 4 Dentali F, Di Micco G, Giorgi Pierfranceschi M. et al. Rate and duration of hospitalization for deep vein thrombosis and pulmonary embolism in real-world clinical practice. Ann Med 2015; 47 (07) 546-554
- 5 Konstantinides SV, Barco S, Lankeit M, Meyer G. Management of pulmonary embolism: an update. J Am Coll Cardiol 2016; 67 (08) 976-990
- 6 Wiener RS, Schwartz LM, Woloshin S. Time trends in pulmonary embolism in the United States: evidence of overdiagnosis. Arch Intern Med 2011; 171 (09) 831-837
- 7 Vinson DR, Mark DG, Chettipally UK. et al; eSPEED Investigators of the KP CREST Network. Increasing safe outpatient management of emergency department patients with pulmonary embolism: a controlled pragmatic trial. Ann Intern Med 2018; 169 (12) 855-865
- 8 Becattini C, Agnelli G, Lankeit M. et al. Acute pulmonary embolism: mortality prediction by the 2014 European Society of Cardiology risk stratification model. Eur Respir J 2016; 48 (03) 780-786
- 9 Goldhaber SZ, Visani L, De Rosa M. Acute pulmonary embolism: clinical outcomes in the International Cooperative Pulmonary Embolism Registry (ICOPER). Lancet 1999; 353 9162 1386-1389
- 10 Casazza F, Becattini C, Bongarzoni A. et al; The Italian Pulmonary Embolism Registry (IPER). Clinical features and short term outcomes of patients with acute pulmonary embolism. Thromb Res 2012; 130 (06) 847-852
- 11 Pollack CV, Schreiber D, Goldhaber SZ. et al. Clinical characteristics, management, and outcomes of patients diagnosed with acute pulmonary embolism in the emergency department: initial report of EMPEROR (Multicenter Emergency Medicine Pulmonary Embolism in the Real World Registry). J Am Coll Cardiol 2011; 57 (06) 700-706
- 12 Laporte S, Mismetti P, Décousus H. et al; RIETE Investigators. Clinical predictors for fatal pulmonary embolism in 15,520 patients with venous thromboembolism: findings from the Registro Informatizado de la Enfermedad TromboEmbolica venosa (RIETE) Registry. Circulation 2008; 117 (13) 1711-1716
- 13 Cohen AT, Gitt AK, Bauersachs R. et al. The management of acute venous thromboembolism in clinical practice. Results from the European PREFER in VTE Registry. Thromb Haemost 2017; 117 (07) 1326-1337
- 14 Haas S, Ageno W, Weitz JI. et al. Anticoagulation therapy patterns for acute treatment of venous thromboembolism in GARFIELD-VTE patients. J Thromb Haemost 2019; 17 (10) 1694-1706
- 15 Cohen AT, Ay C, Hainaut P. et al; ETNA-VTE-Europe investigators. Design and rationale of the non-interventional, edoxaban treatment in routiNe clinical prActice in patients with venous ThromboEmbolism in Europe (ETNA-VTE-Europe) study. Thromb J 2018; 16: 9
- 16 Bounameaux H, Haas S, Farjat AE. et al. Comparative effectiveness of oral anticoagulants in venous thromboembolism: GARFIELD-VTE. Thromb Res 2020; 191: 103-112
- 17 Ortel TL, Neumann I, Ageno W. et al. American Society of Hematology 2020 guidelines for management of venous thromboembolism: treatment of deep vein thrombosis and pulmonary embolism. Blood Adv 2020; 4 (19) 4693-4738
- 18 Giri J, Sista AK, Weinberg I. et al. Interventional therapies for acute pulmonary embolism: current status and principles for the development of novel evidence: a scientific statement from the American Heart Association. Circulation 2019; 140 (20) e774-e801
- 19 Konstantinides SV, Torbicki A, Agnelli G. et al; Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC). 2014 ESC guidelines on the diagnosis and management of acute pulmonary embolism. Eur Heart J 2014; 35 (43) 3033-3069 , 3069a–3069k
- 20 Konstantinides SV, Meyer G, Becattini C. et al; ESC Scientific Document Group. 2019 ESC guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur Heart J 2020; 41 (04) 543-603
- 21 Becattini C, Agnelli G, Maggioni AP. et al. Contemporary clinical management of acute pulmonary embolism: the COPE study. Intern Emerg Med 2022; 17 (03) 715-723
- 22 Jiménez D, Aujesky D, Moores L. et al; RIETE Investigators. Simplification of the pulmonary embolism severity index for prognostication in patients with acute symptomatic pulmonary embolism. Arch Intern Med 2010; 170 (15) 1383-1389
- 23 Petrie MC, McMurray JJV. Do we need clinical events committees to adjudicate end points?. Circ Heart Fail 2020; 13 (07) e007209
- 24 Meah MN, Denvir MA, Mills NL, Norrie J, Newby DE. Clinical endpoint adjudication. Lancet 2020; 395 10240 1878-1882
- 25 Schulman S, Kearon C. Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost 2005; 3 (04) 692-694
- 26 Becattini C, Casazza F, Forgione C. et al. Acute pulmonary embolism: external validation of an integrated risk stratification model. Chest 2013; 144 (05) 1539-1545
- 27 Becattini C, Maraziti G, Vinson DR. et al. Right ventricle assessment in patients with pulmonary embolism at low risk for death based on clinical models: an individual patient data meta-analysis. Eur Heart J 2021; 42 (33) 3190-3199
- 28 Perrier A, Roy PM, Sanchez O. et al. Multidetector-row computed tomography in suspected pulmonary embolism. N Engl J Med 2005; 352 (17) 1760-1768
- 29 van Belle A, Büller HR, Huisman MV. et al; Christopher Study Investigators. Effectiveness of managing suspected pulmonary embolism using an algorithm combining clinical probability, D-dimer testing, and computed tomography. JAMA 2006; 295 (02) 172-179
- 30 Stein PD, Fowler SE, Goodman LR. et al; PIOPED II Investigators. Multidetector computed tomography for acute pulmonary embolism. N Engl J Med 2006; 354 (22) 2317-2327
- 31 van der Hulle T, Cheung WY, Kooij S. et al; YEARS study group. Simplified diagnostic management of suspected pulmonary embolism (the YEARS study): a prospective, multicentre, cohort study. Lancet 2017; 390 10091 289-297
- 32 Olgers TJ, Azizi N, Blans MJ, Bosch FH, Gans ROB, Ter Maaten JC. Point-of-care Ultrasound (PoCUS) for the internist in acute medicine: a uniform curriculum. Neth J Med 2019; 77 (05) 168-176
- 33 Johri AM, Galen B, Kirkpatrick JN, Lanspa M, Mulvagh S, Thamman R. ASE Statement on point-of-care ultrasound during the 2019 novel coronavirus pandemic. J Am Soc Echocardiogr 2020; 33 (06) 670-673
- 34 Vinson DR, Mark DG, Ballard DW. Outpatient management of patients with pulmonary embolism. Ann Intern Med 2019; 171 (03) 228
- 35 Barco S, Schmidtmann I, Ageno W. et al; HoT-PE Investigators. Early discharge and home treatment of patients with low-risk pulmonary embolism with the oral factor Xa inhibitor rivaroxaban: an international multicentre single-arm clinical trial. Eur Heart J 2020; 41 (04) 509-518
- 36 Riera-Mestre A, Jiménez D, Muriel A. et al; RIETE investigators. Thrombolytic therapy and outcome of patients with an acute symptomatic pulmonary embolism. J Thromb Haemost 2012; 10 (05) 751-759