Which heart failure patients profit from natriuretic peptide guided therapy? A meta-analysis from individual patient data of randomized trials

Hans-Peter Brunner-La Rocca*, Luc Eurlings, A. Mark Richards, James L. Januzzi, Matthias E. Pfisterer, Ulf Dahlstrom, Yigal M. Pinto, Patric Karlstrom, Hans Erntell, Rudolf Berger, Hans Persson, Christopher M. O'Connor, Deddo Moertl, Hanna K. Gaggin, Christopher M. Frampton, M. Gary Nicholls, Richard W. Troughton

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Aims Previous analyses suggest that heart failure (HF) therapy guided by (N-terminal pro-)brain natriuretic peptide (NT-proBNP) might be dependent on left ventricular ejection fraction, age and co-morbidities, but the reasons remain unclear. Methods and resultsTo determine interactions between (NT-pro)BNP-guided therapy and HF with reduced [ejection fraction (EF) 45%; HF with reduced EF (HFrEF), n = 1731] vs. preserved EF [EF > 45%; HF with preserved EF (HFpEF), n = 301] and co-morbidities (hypertension, renal failure, chronic obstructive pulmonary disease, diabetes, cerebrovascular insult, peripheral vascular disease) on outcome, individual patient data (n = 2137) from eight NT-proBNP guidance trials were analysed using Cox-regression with multiplicative interaction terms. Endpoints were mortality and admission because of HF. Whereas in HFrEF patients (NT-pro)BNP-guided compared with symptom-guided therapy resulted in lower mortality [hazard ratio (HR) = 0.78, 95% confidence interval (CI) 0.62-0.97, P = 0.03] and fewer HF admissions (HR = 0.80, 95% CI 0.67-0.97, P = 0.02), no such effect was seen in HFpEF (mortality: HR = 1.22, 95% CI 0.76-1.96, P = 0.41; HF admissions HR = 1.01, 95% CI 0.67-1.53, P = 0.97; interactions P <0.02). Age (74 11 years) interacted with treatment strategy allocation independently of EF regarding mortality (P = 0.02), but not HF admission (P = 0.54). The interaction of age and mortality was explained by the interaction of treatment strategy allocation with co-morbidities. In HFpEF, renal failure provided strongest interaction (P <0.01; increased risk of (NT-pro)BNP-guided therapy if renal failure present), whereas in HFrEF patients, the presence of at least two of the following co-morbidities provided strongest interaction (P <0.01; (NT-pro)BNP-guided therapy beneficial only if none or one of chronic obstructive pulmonary disease, diabetes, cardiovascular insult, or peripheral vascular disease present). (NT-pro)BNP-guided therapy was harmful in HFpEF patients without hypertension (P = 0.02). Conclusion The benefits of therapy guided by (NT-pro)BNP were present in HFrEF only. Co-morbidities seem to influence the response to (NT-pro)BNP-guided therapy and may explain the lower efficacy of this approach in elderly patients.
Original languageEnglish
Pages (from-to)1252-1261
JournalEuropean journal of heart failure
Volume17
Issue number12
DOIs
Publication statusPublished - Dec 2015

Keywords

  • Heart failure
  • Biomarkers
  • Co-morbidity
  • Treatment response
  • Heart failure with preserved ejection fraction

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