Fibrinolysis for patients with intermediate-risk pulmonary embolism.
BACKGROUND
The role of fibrinolytic therapy in patients with intermediate-risk pulmonary embolism is controversial.


METHODS
In a randomized, double-blind trial, we compared tenecteplase plus heparin with placebo plus heparin in normotensive patients with intermediate-risk pulmonary embolism. Eligible patients had right ventricular dysfunction on echocardiography or computed tomography, as well as myocardial injury as indicated by a positive test for cardiac troponin I or troponin T. The primary outcome was death or hemodynamic decompensation (or collapse) within 7 days after randomization. The main safety outcomes were major extracranial bleeding and ischemic or hemorrhagic stroke within 7 days after randomization.


RESULTS
Of 1006 patients who underwent randomization, 1005 were included in the intention-to-treat analysis. Death or hemodynamic decompensation occurred in 13 of 506 patients (2.6%) in the tenecteplase group as compared with 28 of 499 (5.6%) in the placebo group (odds ratio, 0.44; 95% confidence interval, 0.23 to 0.87; P=0.02). Between randomization and day 7, a total of 6 patients (1.2%) in the tenecteplase group and 9 (1.8%) in the placebo group died (P=0.42). Extracranial bleeding occurred in 32 patients (6.3%) in the tenecteplase group and 6 patients (1.2%) in the placebo group (P<0.001). Stroke occurred in 12 patients (2.4%) in the tenecteplase group and was hemorrhagic in 10 patients; 1 patient (0.2%) in the placebo group had a stroke, which was hemorrhagic (P=0.003). By day 30, a total of 12 patients (2.4%) in the tenecteplase group and 16 patients (3.2%) in the placebo group had died (P=0.42).


CONCLUSIONS
In patients with intermediate-risk pulmonary embolism, fibrinolytic therapy prevented hemodynamic decompensation but increased the risk of major hemorrhage and stroke. (Funded by the Programme Hospitalier de Recherche Clinique in France and others; PEITHO EudraCT number, 2006-005328-18; ClinicalTrials.gov number, NCT00639743.).
The authors' affiliations are listed in the Appendix.
Guy
G
Meyer
Eric
E
Vicaut
Thierry
T
Danays
Giancarlo
G
Agnelli
Cecilia
C
Becattini
Jan
J
Beyer-Westendorf
Erich
E
Bluhmki
Helene
H
Bouvaist
Benjamin
B
Brenner
Francis
F
Couturaud
Claudia
C
Dellas
Klaus
K
Empen
Ana
A
Franca
Nazzareno
N
Galiè
Annette
A
Geibel
Samuel Z
SZ
Goldhaber
David
D
Jimenez
Matija
M
Kozak
Christian
C
Kupatt
Nils
N
Kucher
Irene M
IM
Lang
Mareike
M
Lankeit
Nicolas
N
Meneveau
Gerard
G
Pacouret
Massimiliano
M
Palazzini
Antoniu
A
Petris
Piotr
P
Pruszczyk
Matteo
M
Rugolotto
Aldo
A
Salvi
Sebastian
S
Schellong
Mustapha
M
Sebbane
Bozena
B
Sobkowicz
Branislav S
BS
Stefanovic
Holger
H
Thiele
Adam
A
Torbicki
Franck
F
Verschuren
Stavros V
SV
Konstantinides
D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005343:Fibrinolytic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006470:Hemorrhage / Q000139:chemically induced; D006493:Heparin / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011655:Pulmonary Embolism / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D012307:Risk Factors; D020521:Stroke / Q000139:chemically induced; D000077785:Tenecteplase; D010959:Tissue Plasminogen Activator / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014336:Troponin / Q000097:blood; D018497:Ventricular Dysfunction, Right / Q000209:etiology
D005343:Fibrinolytic Agents; D014336:Troponin; D006493:Heparin; D010959:Tissue Plasminogen Activator; D000077785:Tenecteplase