Page 49 - Biomarkers for risk stratification and guidance in heart failure

Chapter 3
patients with stable NT-proBNP levels (even when clearly elevated) may have an acceptable prognosis. We hypothesized that elevation of outpatient NT-proBNP levels as compared with the patient’s individualized target level, allows selection of those HF patients most likely to progress towards events. The individualized target level was defined as the lowest level at discharge or at 2 weeks follow-up after admission because of HF. We further hypothesized that restricting treatment intensification to these selected patients would be beneficial without additional risk of adverse effects. We therefore performed a prospective randomized study to address whether treatment of HF, guided by an individualized target NT-proBNP level, improves outcome in HF patients.
METHODS
Study design and study population
PRIMA is a prospective, randomized, single-blind study executed in 12 Dutch university and large general hospitals. Patients were recruited between June 2004 and September 2007. To be included, patients had to be hospitalized for decompensated, symptomatic HF, fulfilling the European Society of Cardiology (ESC) diagnostic guideline criteria for acute HF.9 In addition, NT-proBNP levels at admission were required to be at least 1,700 pg/ml, as additional objective evidence of HF.1 Exclusion criteria were: life-threatening cardiac arrhythmias during the index hospitalization, urgent invasive or surgical intervention performed or planned during the index hospital admission, severe chronic obstructive pulmonary disease with a forced expiratory volume in 1 s (FEV1) of <1 l/s, pulmonary embolism less than 3 months prior to admission, pulmonary hypertension not caused by left ventricular systolic dysfunction, a non-HF-related expected survival of less than 1 year, and patients undergoing hemodialysis or continuous ambulant peritoneal dialysis. A lesser degree of renal dysfunction was not an exclusion criterion. Patients were screened and included during the index admission because of acute HF (Fig. 1). Informed consent was obtained and NT-proBNP levels were measured at hospital discharge. Patients demonstrating a significant decrease in NT-proBNP levels during hospitalization, defined as a decrease of more than 10%, with a drop in NT-proBNP levels of at least 850 pg/ml, were randomized to treatment that was either NT-proBNP-guided or clinically- guided. Patients in whom NT-proBNP levels decreased <10% during admission
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