Impact of Thrombolytic Therapy on the Long-Term Outcome of Intermediate-Risk Pulmonary Embolism.
BACKGROUND
The long-term effect of thrombolytic treatment of pulmonary embolism (PE) is unknown.


OBJECTIVE
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).
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.
Stavros V
SV
Konstantinides
Clinical Research Unit, Fernand-Widal Hospital, Assistance Publique Hôpitaux de Paris, University Paris Diderot, Paris, France.
Eric
E
Vicaut
Boehringer Ingelheim, Reims, France.
Thierry
T
Danays
Department of Internal and Cardiovascular Medicine-Stroke Unit, University of Perugia, Perugia, Italy.
Cecilia
C
Becattini
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.
Laurent
L
Bertoletti
Center for Vascular Diseases, Division of Thrombosis Research, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany.
Jan
J
Beyer-Westendorf
Cardiology Service, Michallon Hospital, Grenoble University Hospital Center, Grenoble, France.
Helene
H
Bouvaist
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).
Francis
F
Couturaud
Cardiology and Pulmonology Clinic, University Medical Center Göttingen, Göttingen, Germany.
Claudia
C
Dellas
Heart Center, University of Freiburg, Freiberg, Germany.
Daniel
D
Duerschmied
Ernst Moritz Arndt Greifswald University Hospital, Greifswald, Germany.
Klaus
K
Empen
Department of Cardiology, University Hospital of Nice, Nice, France.
Emile
E
Ferrari
Department of Experimental, Diagnostic and Specialty Medicine-DIMES, Bologna University Hospital, Bologna, Italy.
Nazzareno
N
Galiè
Department of Respiratory Diseases, Ramon y Cajal Hospital, IRYCIS, Madrid, Spain.
David
D
Jiménez
Department of Internal Medicine and Cardiology, Medical University of Warsaw, Warsaw, Poland.
Maciej
M
Kostrubiec
University Medical Center, Ljubljana, Slovenia.
Matija
M
Kozak
Klinikum Rechts der Isar, TU Munich, and German Center for Cardiovascular Research (DZHK), partner site Munich Heart Alliance, Munich, Germany.
Christian
C
Kupatt
Department of Cardiology, Vienna General Hospital, Medical University of Vienna, Vienna, Austria.
Irene M
IM
Lang
Center for Thrombosis and Hemostasis, University Medical Center, Mainz, Germany; Cardiology and Pulmonology Clinic, University Medical Center Göttingen, Göttingen, Germany.
Mareike
M
Lankeit
Department of Cardiology, Equipe d'Accueil 3920, Structure Fédérative de Recherche 4234, University Hospital Jean Minjoz, Besançon, France (INNOVTE, France).
Nicolas
N
Meneveau
Department of Experimental, Diagnostic and Specialty Medicine-DIMES, Bologna University Hospital, Bologna, Italy.
Massimiliano
M
Palazzini
Department of Internal Medicine and Cardiology, Medical University of Warsaw, Warsaw, Poland.
Piotr
P
Pruszczyk
Department of Cardiology, Ca Foncello Hospital, Treviso, Italy.
Matteo
M
Rugolotto
Azienda Ospedaliero-Universitaria Ospedali Riuniti di Ancona, Ancona, Italy.
Aldo
A
Salvi
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).
Olivier
O
Sanchez
Municipal Hospital of Dresden-Friedrichstadt, Dresden, Germany.
Sebastian
S
Schellong
Medical University, Bialystok, Poland.
Bozena
B
Sobkowicz
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).
Guy
G
Meyer
D000368:Aged; D000369:Aged, 80 and over; D004311:Double-Blind Method; D004452:Echocardiography; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011655:Pulmonary Embolism / Q000000981:diagnostic imaging / Q000401:mortality / Q000517:prevention & control*; D000077785:Tenecteplase; D015912:Thrombolytic Therapy; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D016896:Treatment Outcome
D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator; D000077785:Tenecteplase
chronic thromboembolic pulmonary hypertension; long-term survival; prognosis; pulmonary embolism; thrombolysis