Safety and tolerability of intensified, N-terminal pro brain natriuretic peptide-guided compared with standard medical therapy in elderly patients with congestive heart failure: results from TIME-CHF

Sandra Sanders-van Wijk*, Stefano Muzzarelli, Michael Neuhaus, Stephanie Kiencke, Micha Maeder, Werner Estlinbaum, Daniel Tobler, Kurt Mayer, Paul Erne, Matthias E. Pfisterer, Hans-Peter Brunner-La Rocca

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Aims NT-proBNP-guided therapy results in intensification of medical heart failure (HF) therapy and is suggested to improve outcome. However, it is feared that an intensified, NT-proBNP-guided therapy carries a risk of adverse effects. Therefore, the safety and tolerability of NT-proBNP-guided therapy in the Trial of Intensified vs standard Medical therapy in Elderly patients with Congestive Heart Failure (TIME-CHF) was assessed. Methods and results A total of 495 chronic HF patients, aged >= 60, with an LVEF = II, randomized to NT-proBNP-guided or symptom-guided therapy and >= 1 month follow-up were included in the present safety analysis. All adverse events (AEs) were recorded during the 18-month trial period. A total of 5212 AEs were noted, 433 of them serious. NT-proBNP-guided therapy led to a higher up-titration of HF medication and was well tolerated, with a dropout rate (12% vs. 11%, P = 1.0) and AE profile [number of AEs/patient-year 4.7 (2.8-9.4) vs. 5.4 (2.7-11.4), P = 0.69; number of severe AEs/patient-year 0.7 (0-2.7) vs. 1.3 (0-3.9), P = 0.21] similar to that of symptom-guided therapy, although most subjects in both treatment groups (96% vs. 95%, P = 0.55) experienced at least one AE. Age and number of co-morbidities were associated with AEs and interacted with the safety profile of NT-proBNP-guided therapy: positive effects were more frequent in younger and less co-morbid patients whereas potential negative effects-although small and related to non-severe AEs only-were only seen in the older and more co-morbid patients. Conclusions NT-proBNP-guided therapy is safe in elderly and highly co-morbid HF patients.
Original languageEnglish
Pages (from-to)910-918
JournalEuropean journal of heart failure
Issue number8
Publication statusPublished - Aug 2013


  • Heart failure
  • Natriuretic peptide
  • Safety
  • Drug therapy
  • Ageing
  • Co-morbidities

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