Page 62 - Biomarkers for risk stratification and guidance in heart failure

Management of chronic heart failure guided by individual NT-proBNP targets.
place might help us identify patients at risk for events; in such an early phase,
medical intervention can still avert worse outcome. NT-proBNP appears to be a “passenger-seat” marker: you can see which direction your car is heading, but you
are not in control of the steering wheel. In order to reduce morbidity and mortality,
a “driver-seat” marker is urgently needed. A number of reasons may account for
this lack of significant improvement. First, not enough events during follow-up
may have been detected, as 36% of events were undetected by measurement of
NT-proBNP at 3-month intervals. Second, intensification of treatment against a
background of high use of evidence-based HF therapy may not suffice to avert 3 an imminent event. Third, current “gold-standard” HF therapy may altogether be
inadequate in preventing HF-related events in patients with deterioration of HF.
Subgroups analyzed.
The effects of NT-proBNP guidance seemed mitigated in patients with preserved systolic function, although differences did not reach statistical significance. The lack of well-established medical or other intervention measures for patients with preserved ejection fraction HF may limit the success of interventions prompted by off-target NT-proBNP in this group. The effects of NT-proBNP guidance seemed more favorable in younger patients (age under 75 years) and those with better renal function, although these differences also did not reach statistical significance. Both younger patients and patients with preserved renal function have less comorbidity and are expected to better tolerate intensification of therapy. It is these type of patients that have been included in most landmark trials that yielded the evidence for HF therapy. Elderly patients with severe renal dysfunction and patients with preserved left ventricular systolic function HF form the majority of HF patients, but they are underrepresented in landmark trials.14 Therefore, speculatively, it seems that the intensified use of evidence-based HF therapy is mainly effective in the subgroups where this evidence was obtained. Previous studies have demonstrated that NT-proBNP levels fall in response to optimizing HF therapy.15-17 In PRIMA, intensifying HF therapy in patients with rising NT-proBNP levels failed to lower these levels. The lack of benefit seen in our study is in line with the overall lack of benefit seen with studies of NT-proBNP-guided therapy by an absolute NT-proBNP target.7, 8 PRIMA shows that treatment of HF guided by an individualized NT-proBNP target against a background of optimal HF therapy does not have additional beneficial effects.
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