Page 119 - Biomarkers for risk stratification and guidance in heart failure

Chapter 5
prescription of loop diuretics compared with usual care management.20,22 In the PRIMA study, which failed to demonstrate a significant reduction in end points by NT-proBNP-guided therapy, outpatient elevated NT-proBNP levels led most frequently to an increase in diuretic dosage (>40%).8
Given the association between loop diuretics and worsening of renal function, neurohumoral activation, and adverse outcome in HF,25 the use of diuretics is recommended to be limited to achieve and maintain an euvolemic state with the lowest achievable dose.26
Combining individual risk assessment with the previously mentioned findings from the recent natriuretic peptide-guided therapy studies might lead to an early outpatient individual treatment approach that should be confirmed in future trials. It is assumed that if individual risk for events is low (ie, low composite NT- proBNP score) and a patient is clinically euvolemic, then diuretic dosage should be lowered and outpatient follow-up might be directed to the primary care. If individual risk is high (ie, high composite NT-proBNP score) and the patient is clinically euvolemic, then outpatient follow-up should be intensified at a dedicated outpatient HF clinic with extra attention being paid to compliance and intensified prescription of evidence-based HF medication. If clinical signs of overt or worsening HF occur, diuretic dosage should be increased first, followed by intensification of evidencebased HF medication. However, as already said, large randomized trials are needed to further clarify this issue.
Study Limitations
There are some limitations to the present study. It should be emphasized that the composite NT-proBNP score was calculated to visualize the incremental value of serial NT-proBNP measurements during and early after admission because of acute HF. It was not the intention to develop a risk score that can be used in clinical practice. The NT-proBNP cutpoints were defined from patients included in the PRIMA study. To be included in the PRIMA study, NT-proBNP concentration during admission needed to decrease ≥10% with a minimum of 850 pg/mL. Therefore, we cannot extrapolate our results to patients with a smaller decrease, or an increase in NT-proBNP concentration, during admission. Also, as this study is a post hoc analysis, results remain to be validated by another, preferably larger, prospective study.
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