Fibrinolysis for patients with intermediate-risk pulmonary embolism.

Abstract

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.).

• Authors: Guy Meyer, Eric Vicaut, Thierry Danays, Giancarlo Agnelli, Cecilia Becattini, Jan Beyer-Westendorf, Erich Bluhmki, Helene Bouvaist, Benjamin Brenner, Francis Couturaud, Claudia Dellas, Klaus Empen, Ana Franca, Nazzareno Galiè, Annette Geibel, Samuel Z Goldhaber, David Jimenez, Matija Kozak, Christian Kupatt, Nils Kucher, Irene M Lang, Mareike Lankeit, Nicolas Meneveau, Gerard Pacouret, Massimiliano Palazzini, Antoniu Petris, Piotr Pruszczyk, Matteo Rugolotto, Aldo Salvi, Sebastian Schellong, Mustapha Sebbane, Bozena Sobkowicz, Branislav S Stefanovic, Holger Thiele, Adam Torbicki, Franck Verschuren, Stavros V Konstantinides, PEITHO Investigators
• Journal: The New England journal of medicine (N Engl J Med) Vol. 370 Issue 15 Pg. 1402-11 (Apr 10 2014) ISSN: 1533-4406 [Electronic] United States
• PMID: 24716681 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Fibrinolytic Agents
• Troponin
• Heparin
• Tissue Plasminogen Activator
• Tenecteplase

Topics

• Age Factors
• Aged
• Aged, 80 and over
• Double-Blind Method
• Drug Therapy, Combination
• Female
• Fibrinolytic Agents (adverse effects, therapeutic use)
• Hemorrhage (chemically induced)
• Heparin (adverse effects, therapeutic use)
• Humans
• Male
• Middle Aged
• Pulmonary Embolism (complications, drug therapy, mortality)
• Risk Factors
• Stroke (chemically induced)
• Tenecteplase
• Tissue Plasminogen Activator (adverse effects, therapeutic use)
• Treatment Outcome
• Troponin (blood)
• Ventricular Dysfunction, Right (etiology)