Thromb Haemost
DOI: 10.1055/s-0039-1692424
Stroke, Systemic or Venous Thromboembolism
Georg Thieme Verlag KG Stuttgart · New York

Predictors for Residual Pulmonary Vascular Obstruction after Unprovoked Pulmonary Embolism: Implications for Clinical Practice—The PADIS-PE Trial

Leela Raj
1  Département de Médecine Interne et Pneumologie, Centre Hospitalo-Universitaire de Brest, Université de Bretagne Occidentale, and EA 3878, CIC INSERM 1412, Brest, France
2  Faculty of Heath Science, McMaster University, Hamilton, Ontario, Canada
,
Philippe Robin
3  Service de Médecine Nucléaire and EA 3878, Centre Hospitalo-Universitaire de Brest, Université de Bretagne Occidentale, Brest, France
4  F-CRIN INNOVTE, Saint Etienne, France
,
Raphael Le Mao
1  Département de Médecine Interne et Pneumologie, Centre Hospitalo-Universitaire de Brest, Université de Bretagne Occidentale, and EA 3878, CIC INSERM 1412, Brest, France
4  F-CRIN INNOVTE, Saint Etienne, France
,
Emilie Presles
4  F-CRIN INNOVTE, Saint Etienne, France
5  Unité de recherche clinique, Innovation et pharmacologie, Centre Hospitalo-Universitaire de Saint-Etienne, and INSERM U1059 SAINBIOSE, Université Jean Monnet, Saint-Etienne, France
,
Cécile Tromeur
1  Département de Médecine Interne et Pneumologie, Centre Hospitalo-Universitaire de Brest, Université de Bretagne Occidentale, and EA 3878, CIC INSERM 1412, Brest, France
4  F-CRIN INNOVTE, Saint Etienne, France
,
Olivier Sanchez
4  F-CRIN INNOVTE, Saint Etienne, France
6  Université Paris Descartes, Université Sorbonne Paris Cité, Service de Pneumologie et de soins intensifs, Hôpital Européen Georges Pompidou, AP-HP; Université Paris Descartes, Sorbonne Paris Cité, and INSERM UMR S 1140, Paris, France
,
Gilles Pernod
4  F-CRIN INNOVTE, Saint Etienne, France
7  Département de Médecine Vasculaire, Centre Hospitalo-Universitaire de Grenoble, Université de Grenoble 1, Grenoble, France
,
Laurent Bertoletti
4  F-CRIN INNOVTE, Saint Etienne, France
8  Service de Médecine Vasculaire et Thérapeutique, Unité de Pharmacologie Clinique, CIC1408, Centre Hospitalo-Universitaire de Saint-Etienne, and INSERM U1059 SAINBIOSE, Université Jean Monnet, Saint-Etienne, France
,
Patrick Jego
4  F-CRIN INNOVTE, Saint Etienne, France
9  Service de Médecine Interne, Centre Hospitalo-Universitaire de Rennes, Université de Rennes 1, Rennes, France
,
Florent Leven
10  Service de Cardiologie and EA 3878, Centre Hospitalo-Universitaire de Brest, Université de Bretagne Occidentale, Brest, France
,
Catherine A. Lemarié
1  Département de Médecine Interne et Pneumologie, Centre Hospitalo-Universitaire de Brest, Université de Bretagne Occidentale, and EA 3878, CIC INSERM 1412, Brest, France
4  F-CRIN INNOVTE, Saint Etienne, France
,
Aurore Martin
11  Service d'Echo-doppler Vasculaire, and EA 3878, CIC INSERM 1412, Centre Hospitalo-Universitaire de Brest, Université de Bretagne Occidentale, Brest, France
,
Benjamin Planquette
4  F-CRIN INNOVTE, Saint Etienne, France
6  Université Paris Descartes, Université Sorbonne Paris Cité, Service de Pneumologie et de soins intensifs, Hôpital Européen Georges Pompidou, AP-HP; Université Paris Descartes, Sorbonne Paris Cité, and INSERM UMR S 1140, Paris, France
,
Pierre-Yves Le Roux
3  Service de Médecine Nucléaire and EA 3878, Centre Hospitalo-Universitaire de Brest, Université de Bretagne Occidentale, Brest, France
4  F-CRIN INNOVTE, Saint Etienne, France
,
Pierre-Yves Salaun
3  Service de Médecine Nucléaire and EA 3878, Centre Hospitalo-Universitaire de Brest, Université de Bretagne Occidentale, Brest, France
4  F-CRIN INNOVTE, Saint Etienne, France
,
Michel Nonent
12  Service de Radiologie, and EA 3878, CIC INSERM 1412, Centre Hospitalo-Universitaire de Brest, Université de Bretagne Occidentale, Brest, France
,
Philippe Girard
4  F-CRIN INNOVTE, Saint Etienne, France
13  Département Thoracique, Institut Mutualiste Montsouris, Paris, France
,
Karine Lacut
1  Département de Médecine Interne et Pneumologie, Centre Hospitalo-Universitaire de Brest, Université de Bretagne Occidentale, and EA 3878, CIC INSERM 1412, Brest, France
4  F-CRIN INNOVTE, Saint Etienne, France
,
Solen Melac
1  Département de Médecine Interne et Pneumologie, Centre Hospitalo-Universitaire de Brest, Université de Bretagne Occidentale, and EA 3878, CIC INSERM 1412, Brest, France
4  F-CRIN INNOVTE, Saint Etienne, France
,
Patrick Mismetti
4  F-CRIN INNOVTE, Saint Etienne, France
8  Service de Médecine Vasculaire et Thérapeutique, Unité de Pharmacologie Clinique, CIC1408, Centre Hospitalo-Universitaire de Saint-Etienne, and INSERM U1059 SAINBIOSE, Université Jean Monnet, Saint-Etienne, France
,
Silvy Laporte
4  F-CRIN INNOVTE, Saint Etienne, France
5  Unité de recherche clinique, Innovation et pharmacologie, Centre Hospitalo-Universitaire de Saint-Etienne, and INSERM U1059 SAINBIOSE, Université Jean Monnet, Saint-Etienne, France
,
Guy Meyer
4  F-CRIN INNOVTE, Saint Etienne, France
6  Université Paris Descartes, Université Sorbonne Paris Cité, Service de Pneumologie et de soins intensifs, Hôpital Européen Georges Pompidou, AP-HP; Université Paris Descartes, Sorbonne Paris Cité, and INSERM UMR S 1140, Paris, France
,
Christophe Leroyer
1  Département de Médecine Interne et Pneumologie, Centre Hospitalo-Universitaire de Brest, Université de Bretagne Occidentale, and EA 3878, CIC INSERM 1412, Brest, France
4  F-CRIN INNOVTE, Saint Etienne, France
,
Francis Couturaud
1  Département de Médecine Interne et Pneumologie, Centre Hospitalo-Universitaire de Brest, Université de Bretagne Occidentale, and EA 3878, CIC INSERM 1412, Brest, France
4  F-CRIN INNOVTE, Saint Etienne, France
,
for the PADIS-PE Investigators› Author Affiliations
Funding This study was supported by grants from the “Programme Hospitalier de Recherche Clinique” (French Department of Health), and the sponsor was the University Hospital of Brest. The funding source was not involved in designing or conducting the study, collecting, managing, analyzing, or interpreting the data, preparing, reviewing, or approving the manuscript, or deciding to submit this for publication.
Further Information

Publication History

10 February 2019

17 April 2019

Publication Date:
23 June 2019 (eFirst)

Abstract

Background We aimed to identify risk factors for residual pulmonary vascular obstruction after a first unprovoked pulmonary embolism (PE).

Methods Analyses were based on data from the double-blind randomized “PADIS-PE” trial that included 371 patients with a first unprovoked PE initially treated during 6 uninterrupted months; all patients underwent baseline ventilation–perfusion lung scanning at inclusion (i.e., after 6 months of anticoagulation). Each patient's pulmonary vascular obstruction indexes (PVOIs) at PE diagnosis and at inclusion were centrally assessed.

Results Among the 371 included patients, residual PVOI was available in 356 patients, and 150 (42.1%) patients had PVOI ≥ 5%. At multivariable analysis, age > 65 years (odds ratio [OR], 2.81, 95% confidence interval [CI], 1.58–5.00), PVOI ≥ 25% at PE diagnosis (OR, 3.53, 95% CI, 1.94–6.41), elevated factor VIII (OR, 3.89, 95% CI, 1.41–10.8), and chronic respiratory disease (OR, 2.18, 95% CI, 1.11–4.26) were independent predictors for residual PVOI ≥ 5%. Patients with ≥ 1 of these factors represented 94.5% (123 patients) of all patients with residual PVOI ≥ 5%.

Conclusion Six months after a first unprovoked PE, age > 65 years, PVOI ≥ 25% at PE diagnosis, elevated factor VIII, or chronic respiratory disease were found to be independent predictors for residual pulmonary vascular obstruction.

Clinical Trials Registration URL: http://www.controlled-trials.com. Unique identifier: NCT00740883.

Authors' Contributions

F.C. had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. He obtained funding for the manuscript and supervised the study. F.C., L.R., O.S., L.B., C.T., P.M., and C.L. contributed to study concept and design. F. C., L.R., O.S., C.T., G.M., L.B., S.L., P.G., E.P., and C.L. contributed to drafting of the manuscript. S.M. contributed to acquisition of data. S.L., E.P., and F.C. contributed to statistical analysis. F.C., K.L., P.Y.S, L.B., M.N., and C.L. provided administrative, technical, or material support. All the authors contributed to analysis and interpretation of data and critical revision of the manuscript for important intellectual content. All the authors approved the final manuscript.


* Members of the Prolongation d'un traitement par Antivitamine K pendant Dix-huit mois versus placebo au décours d'un premier épisode d'embolie pulmonaire Idiopathique traité Six mois (PADIS-PE) Study Group are listed in [Supplementary Appendix] (available in the online version).


Supplementary Material