Page 48 - Biomarkers for risk stratification and guidance in heart failure

Management of chronic heart failure guided by individual NT-proBNP targets.
INTRODUCTION
Current management of patients with heart failure (HF) is mainly based on clinical
signs and symptoms. This approach allows clinicians to respond to worsening HF
once it is recognized, but does not allow selection of individuals who are most
likely to progress to increased morbidity and mortality and are thus in need of
more intensive treatment. Plasma levels of B-type natriuretic peptide (BNP) or
N-terminal pro-B-type natriuretic peptide (NT-proBNP) are established indicators
of decompensated HF1, 2 and predictors of HF morbidity and mortality.3, 4 Natriuretic 3 peptides may therefore be attractive biomarkers to guide management of HF and
help select patients in need of more aggressive therapy. Troughton et al.5 were the first to suggest in a small pilot study that guiding HF management by aiming for a target NT-proBNP level may improve outcome. In this study, the investigators aimed to achieve NT-proBNP levels of 200 pmol/l (1,700 pg/ml) or lower, a goal that is difficult to achieve in many patients with established HF. The clinical value of such stringent (NT-pro)BNP levels has recently been addressed in several other clinical outcome studies.6-8 These studies failed to show an overall reduction in mortality, but did suggest improved outcome in HF patients under the age of 75 years. Also, the (NT-pro)BNP target value was achieved only in a minority of patients. In the STARS-BNP (Systolic Heart Failure Treatment Supported by BNP) Multicenter study, only 33% reached the BNP target,6 whereas in TIME-CHF (Trial of Intensified vs Standard Medical Therapy in Elderly Patients With Congestive Heart Failure)8 and the BATTLESCARRED (NT-proBNP-Assisted Treatment to Lessen Serial Cardiac Readmissions and Death) trial,7 at least 50% of the subjects had not achieved the desired target at the end of the study. At the same time, the TIME-CHF investigators speculated that intensification of therapy might be harmful in the elderly.8 As the target NT-proBNP level in the aforementioned studies was not achieved in the majority of HF patients randomized to (NT-pro)BNP–guided therapy, most subjects randomized to the (NT-pro)BNP–guided arms received intensified treatment. These studies therefore show that a more generalized intensification of HF therapy may be beneficial in specific subgroups. However, it was not addressed whether serial assessment of NT-proBNP enables to select patients at risk of increased morbidity and mortality. Therefore, the question remains whether it is beneficial to intensify HF therapy only in those patients most likely to progress towards events. It is well known that in many HF patients, NT-proBNP levels never normalize, whereas these patients still remain clinically stable over years. This suggests that
47