Background: The concept of natriuretic peptide guidance has been extensively studied in patients with chronic heart failure (HF), with only limited success. The effect of NT-proBNP (N-terminal probrain natriuretic peptide)-guided therapy in patients with acute decompensated HF using a relative NT-proBNP target has not been investigated. This study aimed to assess whether NT-proBNP-guided therapy of patients with acute decompensated HF using a relative NT-proBNP target would lead to improved outcomes compared with conventional therapy. Methods: We conducted a prospective randomized controlled trial to study the impact of in-hospital guidance for acute decompensated HF treatment by a predefined NT-proBNP target (>30% reduction from admission to discharge) versus conventional treatment. Patients with acute decompensated HF with NT-proBNP levels >1700 ng/L were eligible. After achieving clinical stability, 405 patients were randomized to either NT-proBNP-guided or conventional treatment (1:1). The primary end point was dual: a composite of all-cause mortality and HF readmissions in 180 days and the number of days alive out of the hospital in 180 days. Secondary end points were all-cause mortality within 180 days, HF readmissions within 180 days, and a composite of all-cause mortality and HF readmissions within 90 days. Results: Significantly more patients in the NT-proBNP-guided therapy group were discharged with an NT-proBNP reduction of >30% (80% versus 64%, P =0.001). Nonetheless, NT-proBNP-guided therapy did not significantly improve the combined event rate for all-cause mortality and HF readmissions (hazard ratio, 0.96; 95% confidence interval, 0.72–1.37; P =0.99) or the median number of days alive outside of the hospital (178 versus 179 days for NT-proBNP versus conventional patients, P =0.39). Guided therapy also did not significantly improve any of the secondary end points. Conclusions: The PRIMA II trial (Can NT-ProBNP-Guided Therapy During Hospital Admission for Acute Decompensated Heart Failure Reduce Mortality and Readmissions?) demonstrates that the guidance of HF therapy to reach an NT-proBNP reduction of >30% after clinical stabilization did not improve 6-month outcomes. Clinical Trial Registration: URL: http://www.trialregister.nl . Unique identifier: NTR3279.

Guideline-directed medical therapy (GDMT) has clear benefits on morbidity and mortality in patients with heart failure; however, GDMT use remains low. In the multicenter, open-label, investigator-initiated ADMINISTER trial, patients (n = 150) diagnosed with heart failure and reduced ejection fraction (HFrEF) were randomized (1:1) to receive usual care or a strategy using digital consults (DCs). DCs contained (1) digital data sharing from patient to clinician (pharmacotherapy use, home-measured vital signs and Kansas City Cardiomyopathy Questionnaires); (2) patient education via a text-based e-learning; and (3) guideline recommendations to all treating clinicians. All remotely gathered information was processed into a digital summary that was available to clinicians in the electronic health record before every consult. All patient interactions were standardly conducted remotely. The primary endpoint was change in GDMT score over 12 weeks (ΔGDMT); this GDMT score directly incorporated all non-conditional class 1 indications for HFrEF therapy with equal weights. The ADMINISTER trial met its primary outcome of achieving a higher GDMT in the DC group after a follow-up of 12 weeks (ΔGDMT score in the DC group: median 1.19, interquartile range (0.25, 2.3) arbitrary units versus 0.08 (0.00, 1.00) in usual care; P < 0.001). To our knowledge, this is the first multicenter randomized controlled trial that proves a DC strategy is effective to achieve GDMT optimization. ClinicalTrials.gov registration: NCT05413447.