n terminal pro b type natriuretic peptide guided therapy in chronic heart failure reduces repeated hospitalizations results from time chf

Accepted Manuscript Title: NT-proBNP Guided Therapy in Chronic Heart Failure Reduces Repeated Hospitalizations – Results From TIME-CHF Author: Nasser Davarzani, Sandra Sanders-van Wijk, Joël Karel, Micha T Maeder, Gregor Leibundgut, Marc Gutmann, Matthias E Pfisterer, Peter Rickenbacher, Ralf Peeters, Hans-Peter Brunner-La Rocca PII: DOI: Reference: S1071-9164(17)30034-9 http://dx.doi.org/doi: 10.1016/j.cardfail.2017.02.001 YJCAF 3921 To appear in: Journal of Cardiac Failure Received date: Revised date: Accepted date: 15-4-2016 29-11-2016 8-2-2017 Please cite this article as: Nasser Davarzani, Sandra Sanders-van Wijk, Joël Karel, Micha T Maeder, Gregor Leibundgut, Marc Gutmann, Matthias E Pfisterer, Peter Rickenbacher, Ralf Peeters, Hans-Peter Brunner-La Rocca, NT-proBNP Guided Therapy in Chronic Heart Failure Reduces Repeated Hospitalizations – Results From TIME-CHF, Journal of Cardiac Failure (2017), http://dx.doi.org/doi: 10.1016/j.cardfail.2017.02.001 This is a PDF file of an unedited manuscript that has been accepted for publication As a service to our customers we are providing this early version of the manuscript The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain NT-proBNP guided therapy in chronic heart failure reduces repeated hospitalizations – results from TIME-CHF Nasser Davarzani1,2,*, PhD; Sandra Sanders-van Wijk2, MD; Joël Karel1, PhD; Micha T Maeder3, MD; Gregor Leibundgut4, MD; Marc Gutmann4, MD; Matthias E Pfisterer5, MD; Peter Rickenbacher6, MD; Ralf Peeters1, PhD; Hans-Peter Brunner-La Rocca2,5, MD (1) Maastricht University, Department of Data Science and Knowledge Engineering, Maastricht, the Netherlands (2) Maastricht University Medical Center, Department of Cardiology, Maastricht, the Netherlands (3) Kantonsspital St Gallen, Department of Cardiology, St Gallen, Switzerland (4) University Hospital Liestal, Department of Cardiology, Liestal, Switzerland (5) University Hospital Basel, Department of Cardiology, Basel, Switzerland (6) University Hospital Bruderholz, Department of Cardiology, Bruderholz, Switzerland *Address of correspondence: Maastricht University, Department of Data Science and Knowledge Engineering, St Servaasklooster 39, P.O Box 616, 6200 MD, Maastricht, the Netherlands Tel: +31 (0)43 38 84803 Email: n.davarzani@maastrichtuniversity.nl Page of 23 Highlights    Recurrent events are common in patients with heart failure, though hardly analyzed Recurrent events may reveal effects not seen by time-to-first event analysis Gap-time method may be helpful to analyses recurrent events ABSTRACT Background: Although heart failure (HF) patients are known to experience repeated hospitalizations, most studies only evaluated time-to-first event N-terminal Brain 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, using a time-between-events approach in a hypothesis generating analysis Methods and Results: TIME-CHF randomized 499 HF patients, aged ≥60 years, LVEF≤45%, NYHA ≥II to NT-proBNP-guided versus a symptom-guided therapy for 18 months, with further follow-up for 5½ years The effect of NT-proBNP-guided therapy on recurrent HFrelated and all-cause hospitalizations and/or all-cause death was explored Hundred-four patients (49 NT-proBNP-guided, 55 symptom-guided) experienced one and 275 patients (133 NT-proBNP-guided, 142 symptom-guided) two or more all-cause hospitalization events Regarding HF hospitalization, 132 patients (57 NT-proBNP-guided, 75 symptom-guided) experienced one and 122 patients (57 NT-proBNP-guided, 65 symptom-guided) two or more events NT-proBNP-guided therapy was significant in preventing second all cause hospitalizations (Hazard Ratio (HR)= 0.83, P=0.01) in contrast to non-significant results in preventing first all-cause hospitalization events (HR=0.91, P=0.35) This was not the case regarding HF hospitalization events (HR= 0.85, P=0.14 vs HR =0.73, P= 0.01) The beneficial Page of 23 effect of NT-proBNP-guided therapy was only seen in patients aged