Page 63 - Biomarkers for risk stratification and guidance in heart failure
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                                Chapter 3
Study limitations
As opposed to what could be expected from large HF surveys,18 only a minority of patients included in our study had a history of HF. NT-proBNP levels might decrease more in response to HF treatment in patients with de novo HF compared with patients with a history of HF and background therapy before admission. Because we excluded patients if NT-proBNP levels decreased <10%, with a minimum of 850 pg/ml, more patients with a history of HF and prolonged exposure to therapy might be excluded than patients with de novo HF. Power analysis was based on the initial primary end point of reduction in events.
Sample size was calculated to demonstrate a minimum reduction in pooled events of 30%. A post hoc power analysis indicated that a difference of 4% in percentage of time (approximately 28 days) alive outside the hospital could have been detected. One may surmise that choosing an individual (often elevated) NT- proBNP target is not accurate enough, and that more stringent targets should be aimed for in all subjects. However, the prognostic impact we observed of NT- proBNP levels above the individual target, even when the target is clearly elevated, argues against this notion.
Furthermore, the most common reaction to an elevated NT-proBNP level was to increase dosage of diuretics. We have not been able to demonstrate the ability of any subtype of intervention (evidence-based medication, diuretics, or non- pharmacologic) to be more effective in lowering off-target NT-proBNP levels. The use of our electronic therapy advisor might have led to more intensified treatment in the clinically-guided group than would occur in daily practice where such advices are not generated. Previous studies have demonstrated that discharge NT-proBNP levels, decrease in NT-proBNP levels during admission because of HF, and outpatient NT-proBNP levels in patients with stable, chronic HF were of prognostic importance.4, 19, 20 The possible additive value of a combination of static and dynamic NT-proBNP levels for determining individual prognosis still remains to be assessed.
Conclusions
This is the first study to our knowledge that evaluated whether HF therapy guided by an individualized NT-proBNP target level improves outcome. PRIMA shows that unstable NT-proBNP levels indeed indicate imminent events, but that intensification of currently used medication in patients on optimal HF therapy does not prevent further deterioration.
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