Page 68 - Biomarkers for risk stratification and guidance in heart failure

Management of chronic heart failure guided by individual NT-proBNP targets.
The hypothesis that BNP levels could be used to guide therapy is appealing as it
offers the possibility of individualizing therapy according to an objective measure
of function and risk. With this strategy, patients with high BNP/ NT-proBNP levels—
who are at higher risk for adverse events—are targeted to receive higher doses of
medications that are proven to increase survival. Conversely, patients with low
or normal peptide levels are spared higher doses that may be associated with
adverse medication effects. To date, 5 published studies have tested this strategy,
with slightly different study designs, but all with 1 central characteristic that an
absolute peptide level was targeted in the treatment group assigned to BNP- 3 or NT-proBNP-guided care.4-8 In the largest of these studies—TIME-CHF (Trial of
Intensified vs Standard Medical Therapy in Elderly Patients With Congestive Heart
Failure)— a higher NT-proBNP level was used as a target for subjects over 75 years
of age (800 pg/ml) compared with those ages 60 to 74 years (400 pg/ml).7 Findings
from these 5 studies have varied, with some documenting significant clinical
benefit from biomarker-guided management, at least in younger patients,4-7 but
2 larger studies reporting no overall improvement in clinical outcomes or quality
of life.5,7
Critics of the concept of biomarker-guided treatment of heart failure question the need for a biomarker to prompt up-titration of proven therapy, stating that all patients should automatically be titrated to tolerated maximal dose.2 They also note that common peptide targets were frequently not achieved in earlier biomarker-guided studies and suggest that individualized targets may be more achievable. In the face of confounders of BNP/NT-proBNP levels, such as renal dysfunction, myocardial ischemia, and atrial fibrillation, some critics of biomarker-guided treatment question whether a true feedback loop can be achieved and whether peptide levels can be consistently lowered by intensifying therapy. Others have expressed caution in using the biomarker approach in view of intrapatient variability of natriuretic peptide levels.21
In a novel study published in this issue of the Journal, Eurlings et al.22 address 1 criticism of earlier studies by testing an individualized NT-proBNP level as a target. The PRIMA (Can PRo-brain-natriuretic peptide-guided therapy of chronic heart failure IMprove heart fAilure morbidity and mortality?) study recruited 345 patients who had been hospitalized with decompensated symptomatic heart failure. Eligibility required an NT-proBNP level >1,700 pg/ml (a higher level than other biomarker-guided studies), and subjects also had to demonstrate a fall in NT-
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