Effect of Natriuretic Peptide-Guided Therapy on Outcomes in High-Risk Patients with Heart Failure and Reduced Ejection Fraction: A Randomized Clinical Trial

Introduction: The natriuretic peptides, specifically B-type natriuretic peptide (BNP) and aminoterminal pro–B-type natriuretic peptide (NT-proBNP), are biochemical markers of heart failure (HF) severity and predictors of adverse outcomes. Smaller studies have evaluated adjusting HF therapy based on natriuretic peptide levels (“guided therapy”) with inconsistent results. Hypothesis: A strategy of NT-proBNP-guided treatment improves clinical outcomes compared to usual care in high-risk patients with HF and reduced ejection fraction (HFrEF). Methods: The GUIDing Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure (GUIDE-IT) study was a randomized multi-center clinical trial conducted between January 2013 and December 2016 at 45 clinical sites in the United States and Canada. This study planned to randomize 1100 patients with HFrEF (ejection fraction ≤40%), elevated natriuretic peptide levels within the prior 30 days, and a history of a prior HF event (HF hospitalization or equivalent) to either an NT-proBNP-guided strategy or usual care. Patients were randomized to either an NT-proBNP-guided strategy or usual care. Patients randomized to the guided strategy had HF therapy titrated with the goal of achieving a target NT-proBNP <1000 pg/mL. Patients randomized to usual had heart failure care in accordance with published guidelines. The primary endpoint was the composite of time-to-first HF hospitalization or cardiovascular mortality. Prespecified secondary endpoints included all-cause mortality, total hospitalizations fr HF, days alive and not hospitalized for cardiovascular reasons, the individual components on the primary endpoint, and safety. Results: The Data and Safety Monitoring Board recommended stopping the study for futility when 894 of the planned 1100 patients had been enrolled and followed for a median of 15 months. The primary endpoint occurred in 164 patients (37%) in the biomarker-guided group and 164 patients (37%) in the usual care group (adjusted hazard ratio = 0.98; 95% confidence interval 0.79–1.22; P = .88). Cardiovascular mortality was 12% in the biomarker guided group and 13% in the usual care group (hazard ratio = 0.94; 95% confidence interval 0.65–1.37, P = .75). Neither other secondary endpoints nor achieved decreases in NT-proBNP levels were significantly different between the groups. Conclusions: In high-risk patients with HFrEF, a strategy of NT-proBNP-guided therapy was not more effective than a usual care strategy in improving outcomes.