Stavros V Konstantinides1, Eric Vicaut2, Thierry Danays3, Cecilia Becattini4, Laurent Bertoletti5, Jan Beyer-Westendorf6, Helene Bouvaist7, Francis Couturaud8, Claudia Dellas9, Daniel Duerschmied10, Klaus Empen11, Emile Ferrari12, Nazzareno Galiè13, David Jiménez14, Maciej Kostrubiec15, Matija Kozak16, Christian Kupatt17, Irene M Lang18, Mareike Lankeit19, Nicolas Meneveau20, Massimiliano Palazzini13, Piotr Pruszczyk15, Matteo Rugolotto21, Aldo Salvi22, Olivier Sanchez23, Sebastian Schellong24, Bozena Sobkowicz25, Guy Meyer26. 1. Center for Thrombosis and Hemostasis, University Medical Center, Mainz, Germany; Department of Cardiology, Democritus University of Thrace, Alexandroupoli, Greece. Electronic address: stavros.konstantinides@unimedizin-mainz.de. 2. Clinical Research Unit, Fernand-Widal Hospital, Assistance Publique Hôpitaux de Paris, University Paris Diderot, Paris, France. 3. Boehringer Ingelheim, Reims, France. 4. Department of Internal and Cardiovascular Medicine-Stroke Unit, University of Perugia, Perugia, Italy. 5. Department of Vascular Medicine and Therapy, Saint-Etienne University Hospital Center, Saint-Etienne, France; INSERM (National Institute of Health and Medical Research) U1059, Saint-Etienne, France; INSERM CIC1408, Saint-Etienne, France. 6. Center for Vascular Diseases, Division of Thrombosis Research, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany. 7. Cardiology Service, Michallon Hospital, Grenoble University Hospital Center, Grenoble, France. 8. Departement of Internal Medicine and Pulmonology, Equipe d'Accueil 3878, CIC INSERM 0502, La Cavale Blanche Hospital, University of Western Brittany, Brest, France (INNOVTE, France). 9. Cardiology and Pulmonology Clinic, University Medical Center Göttingen, Göttingen, Germany. 10. Heart Center, University of Freiburg, Freiberg, Germany. 11. Ernst Moritz Arndt Greifswald University Hospital, Greifswald, Germany. 12. Department of Cardiology, University Hospital of Nice, Nice, France. 13. Department of Experimental, Diagnostic and Specialty Medicine-DIMES, Bologna University Hospital, Bologna, Italy. 14. Department of Respiratory Diseases, Ramon y Cajal Hospital, IRYCIS, Madrid, Spain. 15. Department of Internal Medicine and Cardiology, Medical University of Warsaw, Warsaw, Poland. 16. University Medical Center, Ljubljana, Slovenia. 17. Klinikum Rechts der Isar, TU Munich, and German Center for Cardiovascular Research (DZHK), partner site Munich Heart Alliance, Munich, Germany. 18. Department of Cardiology, Vienna General Hospital, Medical University of Vienna, Vienna, Austria. 19. Center for Thrombosis and Hemostasis, University Medical Center, Mainz, Germany; Cardiology and Pulmonology Clinic, University Medical Center Göttingen, Göttingen, Germany. 20. Department of Cardiology, Equipe d'Accueil 3920, Structure Fédérative de Recherche 4234, University Hospital Jean Minjoz, Besançon, France (INNOVTE, France). 21. Department of Cardiology, Ca Foncello Hospital, Treviso, Italy. 22. Azienda Ospedaliero-Universitaria Ospedali Riuniti di Ancona, Ancona, Italy. 23. Pulmonology and Intensive Care Service, Georges Pompidou European Hospital, Assistance Publique Hôpitaux de Paris, Paris, France; Paris Descartes University, Sorbonne Paris Cité, Paris, France; INSERM UMR S 1140, Paris, France (INNOVTE, France). 24. Municipal Hospital of Dresden-Friedrichstadt, Dresden, Germany. 25. Medical University, Bialystok, Poland. 26. Pulmonology and Intensive Care Service, Georges Pompidou European Hospital, Assistance Publique Hôpitaux de Paris, Paris, France; Paris Descartes University, Sorbonne Paris Cité, Paris, France; INSERM UMR S 970, Paris, France (INNOVTE, France).
Abstract
BACKGROUND: The long-term effect of thrombolytic treatment of pulmonary embolism (PE) is unknown. OBJECTIVES: This study investigated the long-term prognosis of patients with intermediate-risk PE and the effect of thrombolytic treatment on the persistence of symptoms or the development of late complications. METHODS: The PEITHO (Pulmonary Embolism Thrombolysis) trial was a randomized (1:1) comparison of thrombolysis with tenecteplase versus placebo in normotensive patients with acute PE, right ventricular (RV) dysfunction on imaging, and a positive cardiac troponin test result. Both treatment arms received standard anticoagulation. Long-term follow-up was included in the third protocol amendment; 28 sites randomizing 709 of the 1,006 patients participated. RESULTS: Long-term (median 37.8 months) survival was assessed in 353 of 359 (98.3%) patients in the thrombolysis arm and in 343 of 350 (98.0%) in the placebo arm. Overall mortality rates were 20.3% and 18.0%, respectively (p = 0.43). Between day 30 and long-term follow-up, 65 deaths occurred in the thrombolysis arm and 53 occurred in the placebo arm. At follow-up examination of survivors, persistent dyspnea (mostly mild) or functional limitation was reported by 36.0% versus 30.1% of the patients (p = 0.23). Echocardiography (performed in 144 and 146 patients randomized to thrombolysis and placebo, respectively) did not reveal significant differences in residual pulmonary hypertension or RV dysfunction. Chronic thromboembolic pulmonary hypertension (CTEPH) was confirmed in 4 (2.1%) versus 6 (3.2%) cases (p = 0.79). CONCLUSIONS: Approximately 33% of patients report some degree of persistent functional limitation after intermediate-risk PE, but CTEPH is infrequent. Thrombolytic treatment did not affect long-term mortality rates, and it did not appear to reduce residual dyspnea or RV dysfunction in these patients. (Pulmonary Embolism Thrombolysis study [PEITHO]; NCT00639743).
RCT Entities:
BACKGROUND: The long-term effect of thrombolytic treatment of pulmonary embolism (PE) is unknown. OBJECTIVES: This study investigated the long-term prognosis of patients with intermediate-risk PE and the effect of thrombolytic treatment on the persistence of symptoms or the development of late complications. METHODS: The PEITHO (Pulmonary Embolism Thrombolysis) trial was a randomized (1:1) comparison of thrombolysis with tenecteplase versus placebo in normotensive patients with acute PE, right ventricular (RV) dysfunction on imaging, and a positive cardiac troponin test result. Both treatment arms received standard anticoagulation. Long-term follow-up was included in the third protocol amendment; 28 sites randomizing 709 of the 1,006 patients participated. RESULTS: Long-term (median 37.8 months) survival was assessed in 353 of 359 (98.3%) patients in the thrombolysis arm and in 343 of 350 (98.0%) in the placebo arm. Overall mortality rates were 20.3% and 18.0%, respectively (p = 0.43). Between day 30 and long-term follow-up, 65 deaths occurred in the thrombolysis arm and 53 occurred in the placebo arm. At follow-up examination of survivors, persistent dyspnea (mostly mild) or functional limitation was reported by 36.0% versus 30.1% of the patients (p = 0.23). Echocardiography (performed in 144 and 146 patients randomized to thrombolysis and placebo, respectively) did not reveal significant differences in residual pulmonary hypertension or RV dysfunction. Chronic thromboembolic pulmonary hypertension (CTEPH) was confirmed in 4 (2.1%) versus 6 (3.2%) cases (p = 0.79). CONCLUSIONS: Approximately 33% of patients report some degree of persistent functional limitation after intermediate-risk PE, but CTEPH is infrequent. Thrombolytic treatment did not affect long-term mortality rates, and it did not appear to reduce residual dyspnea or RV dysfunction in these patients. (Pulmonary Embolism Thrombolysis study [PEITHO]; NCT00639743).
Authors: Tyree H Kiser; Ellen L Burnham; Brendan Clark; P Michael Ho; Richard R Allen; Marc Moss; R William Vandivier Journal: Crit Care Med Date: 2018-10 Impact factor: 7.598
Authors: Tyree H Kiser; Ellen L Burnham; Brendan Clark; P Michael Ho; Richard R Allen; Marc Moss; R William Vandivier Journal: Crit Care Med Date: 2018-12 Impact factor: 7.598