Fibrinolysis for patients with intermediate-risk pulmonary embolism
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, Stavros Konstantinides, Guy Meyer, Eric Vicaut, Thomas Meinertz, Frans van de Werf, Arnaud Perrier, Mareike Lankeit, Philippe Girard, Olivier Sanchez, Stavros Konstantinides, 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, K Janata, I Lang, C Kaulfersch, F Verschuren, S Motte, A Ghuysen, G Meyer, B Planquette, N Meneveau, H Bouvaist, M Sebbanne, I Quere, G Pacouret, B Charbonnier, F Couturaud, J Schmidt, P G Steg, B Tardy, M Laurent, G Roul, J P Schwobb, K Kalife, E Ferrari, C Lorut, X Jacob, F Parent, M Hamon, C Kupatt, K Empen, J Beyer, C Dellas, H Thiele, S Schellong, A Geibel, D Habedank, V Kurowski, L Bruch, C Opitz, U Janssens, M Borst, F J Meyer, A Hartmann, C Espinola-Klein, Michael Kapeliovich, A Salvi, N Galie, M Palazzini, M Rugolotto, L G Pancaldi, G Piovaccari, R M Salvi, M Grazia, G Di Pasquale, G Agnelli, I Enea, V Pengo, P Pruszczyk, M Kostrubiec, B Sobkowicz, M Janion, J D Kasprzak, J Lewczuc, Z Gaciong, T Ryszard, L Polonski, T Judas, C Lohmann, A Petris, C Pop, M Vladoianu, G Tatu-Chitoiu, A C Nechita, L Petrescu, B Stefanovic, G Koracevic, B Putniković, M Kozak, D Jiménez, M Oribe Ibanez, M J Rodriguez, X Pérez Fernandez, C E Cervantes, C Wyss, 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, Stavros Konstantinides, Guy Meyer, Eric Vicaut, Thomas Meinertz, Frans van de Werf, Arnaud Perrier, Mareike Lankeit, Philippe Girard, Olivier Sanchez, Stavros Konstantinides, 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, K Janata, I Lang, C Kaulfersch, F Verschuren, S Motte, A Ghuysen, G Meyer, B Planquette, N Meneveau, H Bouvaist, M Sebbanne, I Quere, G Pacouret, B Charbonnier, F Couturaud, J Schmidt, P G Steg, B Tardy, M Laurent, G Roul, J P Schwobb, K Kalife, E Ferrari, C Lorut, X Jacob, F Parent, M Hamon, C Kupatt, K Empen, J Beyer, C Dellas, H Thiele, S Schellong, A Geibel, D Habedank, V Kurowski, L Bruch, C Opitz, U Janssens, M Borst, F J Meyer, A Hartmann, C Espinola-Klein, Michael Kapeliovich, A Salvi, N Galie, M Palazzini, M Rugolotto, L G Pancaldi, G Piovaccari, R M Salvi, M Grazia, G Di Pasquale, G Agnelli, I Enea, V Pengo, P Pruszczyk, M Kostrubiec, B Sobkowicz, M Janion, J D Kasprzak, J Lewczuc, Z Gaciong, T Ryszard, L Polonski, T Judas, C Lohmann, A Petris, C Pop, M Vladoianu, G Tatu-Chitoiu, A C Nechita, L Petrescu, B Stefanovic, G Koracevic, B Putniković, M Kozak, D Jiménez, M Oribe Ibanez, M J Rodriguez, X Pérez Fernandez, C E Cervantes, C Wyss
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.).
Source: PubMed