title: Efficacy and Safety of Outpatient Treatment Based on the Hestia Clinical Decision Rule with or without N-Terminal Pro-Brain Natriuretic Peptide Testing in Patients with Acute Pulmonary Embolism. A Randomized Clinical Trial.
abstract: Outpatient treatment of pulmonary embolism (PE) may lead to improved patient satisfaction and reduced healthcare costs. However, trials to assess its safety and the optimal method for patient selection are scarce.
  
  
  
  To validate the utility and safety of selecting patients with PE for outpatient treatment by the Hestia criteria and to compare the safety of the Hestia criteria alone with the Hestia criteria combined with N-terminal pro-brain natriuretic peptide (NT-proBNP) testing.
  
  
  
  We performed a randomized noninferiority trial in 17 Dutch hospitals. We randomized patients with PE without any of the Hestia criteria to direct discharge or additional NT-proBNP testing. We discharged the latter patients as well if NT-proBNP did not exceed 500 ng/L or admitted them if NT-proBNP was greater than 500 ng/L. The primary endpoint was 30-day adverse outcome defined as PE- or bleeding-related mortality, cardiopulmonary resuscitation, or intensive care unit admission. The noninferiority margin for the primary endpoint was 3.4%.
  
  
  
  We randomized 550 patients. In the NT-proBNP group, 34 of 275 (12%) had elevated NT-proBNP values and were managed as inpatients. No patient (0 of 34) with an elevated NT-proBNP level treated in hospital (0%; 95% confidence interval [CI], 0-10.2%), versus no patient (0 of 23) with a post hoc-determined elevated NT-proBNP level from the direct discharge group (0%; 95% CI, 0-14.8%), experienced the primary endpoint. In both trial cohorts, the primary endpoint occurred in none of the 275 patients (0%; 95% CI, 0-1.3%) subjected to NT-proBNP testing, versus in 3 of 275 patients (1.1%; 95% CI, 0.2-3.2%) in the direct discharge group (P = 0.25). During the 3-month follow-up, recurrent venous thromboembolism occurred in two patients (0.73%; 95% CI, 0.1-2.6%) in the NT-proBNP group versus three patients (1.1%; 95% CI, 0.2-3.2%) in the direct discharge group (P = 0.65).
  
  
  
  Outpatient treatment of patients with PE selected on the basis of the Hestia criteria alone was associated with a low risk of adverse events. Given the low number of patients with elevated NT-proBNP levels, this trial was unable to draw definite conclusions regarding the incremental value of NT-proBNP testing in patients who fulfill the Hestia criteria. Clinical trial registered with www.trialregister.nl/trialreg/admin/rctview.asp?TC=2603 (NTR2603).
authors.affiliation: 1 Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Paul L
authors.initials: PL
authors.lastname: den Exter
authors.affiliation: 1 Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Wendy
authors.initials: W
authors.lastname: Zondag
authors.affiliation: 1 Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Frederikus A
authors.initials: FA
authors.lastname: Klok
authors.affiliation: 2 Department of Internal Medicine, Reinier de Graaf Hospital, Delft, the Netherlands.
authors.forename: Rolf E
authors.initials: RE
authors.lastname: Brouwer
authors.affiliation: 3 Department of Pulmonary Medicine, Diaconessenhuis, Leiden, the Netherlands.
authors.forename: Janneke
authors.initials: J
authors.lastname: Dolsma
authors.affiliation: 4 Department of Pulmonary Medicine, Medisch Spectrum Twente, Enschede, the Netherlands.
authors.forename: Michiel
authors.initials: M
authors.lastname: Eijsvogel
authors.affiliation: 5 Department of Internal Medicine, Rode Kruis Hospital, Beverwijk, the Netherlands.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Faber
authors.affiliation: 6 Department of Internal Medicine, Haga Hospital, The Hague, the Netherlands.
authors.forename: Marijke
authors.initials: M
authors.lastname: van Gerwen
authors.affiliation: 7 Department of Pulmonary Medicine, Amphia Hospital, Brede, the Netherlands.
authors.forename: Marco J
authors.initials: MJ
authors.lastname: Grootenboers
authors.affiliation: 8 Department of Pulmonary Medicine, Ikazia Hospital, Rotterdam, the Netherlands.
authors.forename: Roxane
authors.initials: R
authors.lastname: Heller-Baan
authors.affiliation: 9 Department of Internal Medicine, Rijnstate Hospital, Arnhem, the Netherlands.
authors.forename: Marcel M
authors.initials: MM
authors.lastname: Hovens
authors.affiliation: 10 Department of Internal Medicine, Rijnland Hospital, Leiderdorp, the Netherlands.
authors.forename: Gé J P M
authors.initials: GJ
authors.lastname: Jonkers
authors.affiliation: 11 Department Pulmonary Medicine, Van Weel Bethesda Hospital, Dirksland, the Netherlands.
authors.forename: Klaas W
authors.initials: KW
authors.lastname: van Kralingen
authors.affiliation: 12 Department of Pulmonary Medicine, Spaarne Hospital, Hoofddorp, the Netherlands.
authors.forename: Christian F
authors.initials: CF
authors.lastname: Melissant
authors.affiliation: 13 Department of Internal Medicine, Groene Hart Hospital, Gouda, the Netherlands.
authors.forename: Henny
authors.initials: H
authors.lastname: Peltenburg
authors.affiliation: 14 Department of Internal Medicine, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Judith P
authors.initials: JP
authors.lastname: Post
authors.affiliation: 15 Department of Internal Medicine, Diakonessenhuis, Utrecht, the Netherlands.
authors.forename: Marcel A
authors.initials: MA
authors.lastname: van de Ree
authors.affiliation: 16 Department of Internal Medicine and.
authors.forename: L Th Tom
authors.initials: LT
authors.lastname: Vlasveld
authors.affiliation: 17 Department of Internal Medicine, Medisch Centrum Haaglanden-Bronovo, The Hague, the Netherlands.
authors.forename: Mariëlle J
authors.initials: MJ
authors.lastname: de Vreede
authors.affiliation: 1 Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Menno V
authors.initials: MV
authors.lastname: Huisman
mesh_terms: D016887:Cardiopulmonary Resuscitation / Q000706:statistics & numerical data; D000072226:Computed Tomography Angiography; D003661:Decision Support Techniques; D005260:Female; D006801:Humans; D007362:Intensive Care Units / Q000706:statistics & numerical data; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010351:Patient Discharge; D010446:Peptide Fragments / Q000097:blood*; D011655:Pulmonary Embolism / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000401:mortality / Q000628:therapy
chemical_list: D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain
keywords: outpatient treatment; pulmonary embolism; risk stratification