Page 160 - Biomarkers for risk stratification and guidance in heart failure

used fixed (NT-pro)BNP target values as treatment goal.44,46-49,53,54 NT-proBNP concentration above 1,000 pg/ml is associated with increased risk in HF.78,79
Therefore, one could argue that solely implementing a fixed (NT-pro)BNP target
should be the most efficient way to treat outpatient HF. However, the fixed and
stringent target values used in these studies were achieved only in a minority of
patients, (table 1). This leads to the question whether treating HF patients upon
such fixed target value selects those patients at highest risk for events and at
highest need for intensified treatment, or that the target value is merely a wake-
up call for the treating physician to consider intensifying treatment in more then
half of the patients. In the PRIMA study we demonstrated that an individualized
NT-proBNP target yielded important prognostic impact (see table 7, chapter 3). Interestingly, in PRIMA, 80% of patients were on their individualized target after
one year of follow-up. In chapter 5 we evaluated the prognostic effect of change
in NT-proBNP during and early after admission because of acute HF. We found
that even modest changes in NT-proBNP one month after hospital discharge
(ie change less then 30%) were of prognostic importance, independent of the
NT-proBNP level at one-month follow-up and change during admission. Also
in outpatient destabilized HF, change in NT-proBNP has been associated with
prognosis: Bayes-Genis et al, for example, reported a 21% reduction in events for
every 10% decrease in NT-proBNP within 2 weeks.80 Thus it seems that both early
after hospital discharge and in outpatient destabilized HF, not only the absolute concentration is of importance, but also whether or not NT-proBNP concentration
is decreasing. Kazanegra et al. have demonstrated that decreasing NT-proBNP
levels reflect improvement of cardiac status81. Therefore we hypothesize that
the most efficient natriuretic peptide target level might be a combination of a 7 fixed and relative target: the primary aim could be to decrease the NT-proBNP concentration < 1,000 pg/ml. However, if subsequent NT-proBNP levels decrease
with more than 10%, it might be considered as on target, even though this level is above this fixed target.
Such strategy would possibly lead to a more selective and individualized risk stratification then implementing a stringent, fixed NT-proBNP level as target alone.
Response to off-target natriuretic peptide levels.
Although some natriuretic peptide-guided therapy studies provided a treatment algorithm, final decision how to react to natriuretic peptide levels that were too
General Discussion
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