Page 50 - Biomarkers for risk stratification and guidance in heart failure

Management of chronic heart failure guided by individual NT-proBNP targets.
were considered not to modulate their NT-proBNP levels enough to allow NT- proBNP-guided treatment. Therefore, these patients were not included.
Regular follow-up visits were scheduled at 2 weeks and 1 month, and then
every 3 months until the follow-up period of 2 years was completed. Follow-up
visits were performed by dedicated HF cardiologists and nurses. The institutional
review board or ethics committee at each site approved the protocol, and all
patients provided written informed consent before enrollment. Treatment in the NT-proBNP-guided group was guided by the combination of clinical assessment
and NT-proBNP levels. The individual NT-proBNP target value was set at the lowest 3 level at discharge or at 2 weeks follow-up. If at subsequent outpatient visits, NT-
proBNP levels were more than 10% with a minimum of 850 pg/ml above this
individual target level, NT-proBNP level was considered “off-target,” and therapy
was intensified according to the ESC HF treatment guidelines.10 In this treatment
group, an electronic case record form indicated at each visit whether NT-proBNP
levels were off-target and indicated whether intensification was necessary.
Therapy in the clinically-guided treatment group was determined by clinical
assessment alone. A therapy advisor, incorporated in the electronic case record
form, was designed to give individual treatment advice, depending on several
individual variables including the cause of HF (ischemic vs. non-ischemic), left
ventricular ejection fraction (LVEF), clinical signs of HF, and creatinine clearance.
Also, titration schemes for diuretics, angiotensin-converting enzyme (ACE)
inhibitors, betablockers, angiotensin receptor blockers, and aldosterone receptor
blockers were provided. In the clinically-guided treatment group, all cardiologists
were blinded to the NT-proBNP levels of the patients during follow-up. At every
outpatient visit, vital status was assessed. Quality of life (QOL) was assessed at
3-month intervals by the Minnesota Living with Heart Failure Questionnaire.11
NT-proBNP levels were measured on a Roche Diagnostics Elecsys platform (Roche Diagnostics Ltd., Rotkreuz, Switzerland) at every participating site, except for 1 center where the NT-proBNP levels of patients randomized to the NT-proBNP- guided group were measured within 24 h in a participating university hospital nearby.
Definition of study end points
The primary end point of the PRIMA (Can PRo-brain-natriuretic peptide-guided therapy of chronic heart failure IMprove heart fAilure morbidity and mortality?) study was defined as the difference in total number of days alive and outside the hospital between the NT-proBNP-guided and the clinically-guided group. This
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