title: N-Terminal Pro-B-Type Natriuretic Peptide-Guided Therapy in Chronic Heart Failure Reduces Repeated Hospitalizations-Results From TIME-CHF.
abstract: BACKGROUND
  Although heart failure (HF) patients are known to experience repeated hospitalizations, most studies evaluated only time to first event. N-Terminal B-type natriuretic peptide (NT-proBNP)-guided therapy has not convincingly been shown to improve HF-specific outcomes, and effects on recurrent all-cause hospitalization are uncertain. Therefore, we investigated the effect of NT-proBNP-guided therapy on recurrent events in HF with the use of a time-between-events approach in a hypothesis-generating analysis.
  
  
  RESULTS
  The Trial of Intensified Versus Standard Medical Therapy in Elderly Patients With Congestive Heart Failure (TIME-CHF) randomized 499 HF patients, aged ≥60 years, left ventricular ejection fraction ≤45%, New York Heart Association functional class ≥I,I to NT-proBNP-guided versus symptom-guided therapy for 18 months, with further follow-up for 5.5 years. The effect of NT-proBNP-guided therapy on recurrent HF-related and all-cause hospitalizations and/or all-cause death was explored. One hundred four patients (49 NT-proBNP-guided, 55 symptom-guided) experienced 1 and 275 patients (133 NT-proBNP-guided, 142 symptom-guided) experienced ≥2 all-cause hospitalization events. Regarding HF hospitalization, 132 patients (57 NT-proBNP-guided, 75 symptom-guided) experienced 1 and 122 patients (57 NT-proBNP-guided, 65 symptom-guided) experienced ≥2 events. NT-proBNP-guided therapy was significant in preventing 2nd all-cause hospitalizations (hazard ratio [HR] 0.83; P = .01), in contrast to nonsignificant results in preventing 1st all-cause hospitalization events (HR 0.91; P = .35). This was not the case regarding HF hospitalization events (HR 0.85 [P = .14] vs HR 0.73 [P = .01]) The beneficial effect of NT-proBNP-guided therapy was seen only in patients aged <75 years, and not in those aged ≥75 years (interaction terms with P = .01 and P = .03 for all-cause hospitalization and HF hospitalization events, respectively).
  
  
  CONCLUSIONS
  NT-proBNP-guided therapy reduces the risk of recurrent events in patients <75 years of age. This included all-cause hospitalization by mainly reducing later events, adding knowledge to the neutral effect on this end point when shown using time-to-first-event analysis only.
  
  
  BACKGROUND
  isrctn.org, identifier: ISRCTN43596477.
authors.affiliation: Department of Data Science and Knowledge Engineering, Maastricht University, Maastricht, The Netherlands; Department of Cardiology, Maastricht University Medical Center, Maastricht, The Netherlands. Electronic address: n.davarzani@maastrichtuniversity.nl.
authors.forename: Nasser
authors.initials: N
authors.lastname: Davarzani
authors.affiliation: Department of Cardiology, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Sandra
authors.initials: S
authors.lastname: Sanders-van Wijk
authors.affiliation: Department of Data Science and Knowledge Engineering, Maastricht University, Maastricht, The Netherlands.
authors.forename: Joël
authors.initials: J
authors.lastname: Karel
authors.affiliation: Department of Cardiology, Kantonsspital St. Gallen, St Gallen, Switzerland.
authors.forename: Micha T
authors.initials: MT
authors.lastname: Maeder
authors.affiliation: Department of Cardiology, University Hospital Liestal, Liestal, Switzerland.
authors.forename: Gregor
authors.initials: G
authors.lastname: Leibundgut
authors.affiliation: Department of Cardiology, University Hospital Liestal, Liestal, Switzerland.
authors.forename: Marc
authors.initials: M
authors.lastname: Gutmann
authors.affiliation: Department of Cardiology, University Hospital Basel, Basel, Switzerland.
authors.forename: Matthias E
authors.initials: ME
authors.lastname: Pfisterer
authors.affiliation: Department of Cardiology, University Hospital Bruderholz, Bruderholz, Switzerland.
authors.forename: Peter
authors.initials: P
authors.lastname: Rickenbacher
authors.affiliation: Department of Data Science and Knowledge Engineering, Maastricht University, Maastricht, The Netherlands.
authors.forename: Ralf
authors.initials: R
authors.lastname: Peeters
authors.affiliation: Department of Cardiology, Maastricht University Medical Center, Maastricht, The Netherlands; Department of Cardiology, University Hospital Basel, Basel, Switzerland.
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Brunner-la Rocca
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D002908:Chronic Disease; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000097:blood* / Q000175:diagnosis* / Q000628:therapy; D006760:Hospitalization / Q000639:trends; D006801:Humans; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010359:Patient Readmission / Q000639:trends*; D010446:Peptide Fragments / Q000097:blood*; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain
keywords: Heart failure; hospitalization; natriuretic peptides peptide; recurrent events