PEITHO - Long-term Follow Up

Short Attention Span Summary

Lytics in the long-term
There has been some thought that thrombolytic therapy for larger PE may improve functional outcome and dyspnea on exertion from chronic pulmonary hypertension, based in part on the MOPPETT trial.  But this study says probably not.  PEITHO studied lytics for submassive PE.  This was the long-term follow up aspect of the study, and it found there was no mortality benefit and no change in dyspnea or pulmonary hypertension at about 3-years post-treatment in those who received lytics.

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Thrombolytic therapy for submassive PE didn't change the incidence of chronic thromboembolic pulmonary hypertension.


Abstract

J Am Coll Cardiol. 2017 Mar 28;69(12):1536-1544. doi: 10.1016/j.jacc.2016.12.039.

Impact of Thrombolytic Therapy on the Long-Term Outcome of Intermediate-Risk Pulmonary Embolism.

Konstantinides SV1, Vicaut E2, Danays T3, Becattini C4, Bertoletti L5, Beyer-Westendorf J6, Bouvaist H7, Couturaud F8, Dellas C9, Duerschmied D10, Empen K11, Ferrari E12, Galiè N13, Jiménez D14, Kostrubiec M15, Kozak M16, Kupatt C17, Lang IM18, Lankeit M19, Meneveau N20, Palazzini M13, Pruszczyk P15, Rugolotto M21, Salvi A22, Sanchez O23, Schellong S24, Sobkowicz B25, Meyer G26.

Author information:

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).

Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

PMID: 28335835