Rationale and design of PRIMA II: A multicenter, randomized clinical trial to study the impact of in-hospital guidance for acute decompensated heart failure treatment by a predefined NT-PRoBNP target on the reduction of readmIssion and Mortality rAtes

Hospital admissions for acute decompensated heart failure (ADHF) are frequent and are accompanied by high percentages of mortality and readmissions. Brain natriuretic peptide (BNP) and the inactive N-terminal fragment of its precursor proBNP (NT-proBNP) are currently the best predictors of prognosis in heart failure (HF) patients. In the setting of chronic HF, studies that performed guidance of therapy by NT-proBNP have had only limited success. For patients with ADHF, retrospective studies have shown that a reduction in NT-proBNP of ≤30% during admission is a significant predictor of HF readmissions and mortality. These data suggest a role for NT-proBNP guidance in the setting of ADHF admissions. The PRIMA II is an investigator-initiated, multicenter, randomized, controlled, prospective 2-arm trial that investigates the impact of inhospital guidance for ADHF treatment by a predefined NT-proBNP target (>30% reduction during admission) on the reduction of readmission and mortality rates within 180 days. Consenting ADHF patients with NT-proBNP levels of >1,700 ng/L are eligible. After achieving clinical stability, a total of 340 patients are randomized to either NT-proBNP-guided or conventional treatment (1:1). The primary end point is dual, that is, a composite of all-cause mortality and readmission for HF in 180 days and the number of days alive out of hospital in 180 days. Secondary end points are readmissions and/or mortality in 180 days, cost effectiveness of hospitalization days in 180 days, readmissions and mortality in 90 days, and quality of life. The PRIMA II trial aims at providing scientific evidence for the use of NT-proBNP-guided therapy compared with conventional treatment in patients admitted for ADH

External Validation of the ELAN-HF Score, Predicting 6-Month All-Cause Mortality in Patients Hospitalized for Acute Decompensated Heart Failure

Background Our aim was to calibrate and externally revalidate the ELAN-HF (European Collaboration on Acute Decompensated Heart Failure) score, to confirm and improve on a previous external validation of the risk score. Methods and Results The ELAN-HF score predicts 6-month all-cause mortality in patients hospitalized for acute decompensated heart failure using absolute and percentage change of NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels in addition to clinical variables. For the external validation, we used the PRIMA II (Can NT-proBNP-Guided Therapy During Hospital Admission for Acute Decompensated Heart Failure Reduce Mortality and Readmissions?) trial. For both data sets, observed versus predicted mortality was compared for the 4 risk categories; and the mean predicted mortality was plotted against the observed mortality with calculation of a correlation coefficient and SEE. The model discriminant ability was determined by comparing the C-statistics for both data sets. The predicted versus actual 6-month mortality values in the derivation cohort were 3.7% versus 3.6% for the low-risk category, 9.4% versus 9.2% for the intermediate-risk category, 24.2% versus 23.5% for the high-risk category, and 54.2% versus 51.1% for the very-high-risk category. The correlation between predicted and observed mortality by deciles was 0.92, with an SEE of ±4%. In the validation cohort, predicted versus actual 6-month mortality values were 3.0% versus 2.2% for the low-risk category, 9.4% versus 8.2% for the intermediate-risk category, 25.0% versus 22.9% for the high-risk category, and 56.8% versus 53.6% for the very-high-risk category. The correlation between predicted and actual mortality by quintiles was 0.99, with an SEE of ±2%. There was no significant difference in C-statistic between the derivation cohort (0.78; 95% CI, 0.74-0.82) and the validation cohort (0.77; 95% CI, 0.69-0.84; P=0.693). Conclusions Our study confirms that the ELAN-HF score predicts accurately 6-month mortality in patients hospitalized for acute decompensated heart failure with the use of easily obtained characteristics