Page 141 - Biomarkers for risk stratification and guidance in heart failure

Chapter 6
acute HF, early after admission because of acute HF, and chronic HF, changes in NT-proBNP were related to outcome.8,10,11
In line with the prognostic impact of changes in (NT-pro)BNP concentration, natriuretic peptide-guided therapy may result in significantly improved outcome. A recently published meta-analysis based on individual trial data29 demonstrated a reduction in mortality by natriuretic peptide-guided therapy (HR 0.62, 95% CI 0.45-0.86, P=0.004). Still, the individual studies failed to come up with a clear- cut treatment algorithm when treating patients according to natriuretic peptide levels. Interestingly, in all individual studies demonstrating a positive effect of natriuretic peptide-guided therapy,30-33 a significant increase in evidence based HF medication was seen in the natriuretic peptide-guided arm compared to the usual care arm. In two other studies also significantly increasing evidence based HF medication, but without improving the primary endpoint, a significant improvement by natriuretic peptide-guided therapy even in mortality was seen in patients aged 75 years or less.34,35 Furthermore, in 2 of these 6 trials, patients allocated to the NT-proBNP-guided therapy arm had fewer prescription of loop diuretics compared to usual care management.30,31
Knowledge of change in NT-proBNP may help identifying the cause and particularly the impact of change in renal function and may therefore have therapeutic implications. Thus, WRF in combination with a decrease in NT- proBNP might reflect intravascular volume depletion or WRF caused by HF medication like ACE-inhibitors. If not severe, it may be acceptable.16 Diuretic therapy may be reduced and limited to achieve and maintain an euvolemia with the lowest achievable dose, given the association between loop diuretics and worsening of renal function, neurohumoral activation and adverse outcome in HF.36 Importantly, evidence based HF medication should not be reduced, but after stabilizing renal function further intensified. An improvement in renal function in combination with a decrease in NT-proBNP might be caused by increased renal perfusion after adequate HF therapy, supporting further intensifying of evidence based HF medication if not yet at maximum in combination with decrease in diuretic therapy. WRF in combination with an increase in NT-proBNP might reflect progression of HF, often with venous congestion, but possible alternative causes for increasing (NT-pro)BNP levels such as significant infection or an additional primarily renal problem must be considered.37 Underlying cause of deterioration needs to be determinedly sought and appropriately treated; this obviously includes treatment of congestion if present. An improvement in renal function
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