Biomarker-Guided Heart Failure Therapy

Study Questions:

Does N-terminal pro–B-type natriuretic peptide (NT-proBNP)–guided treatment strategy improve clinical outcomes versus usual care in high-risk patients with heart failure and reduced ejection fraction (HFrEF)?


The GUIDE-IT (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure) study was a randomized multicenter clinical trial conducted between January 16, 2013, and September 20, 2016, at 45 clinical sites in the United States and Canada. It randomized patients with HFrEF (left ventricular EF [LVEF] ≤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 (n = 446) and had HF therapy titrated with the goal of achieving a target NT-proBNP of <1000 pg/ml, or usual care (n = 448). Patients randomized to usual care had HF care in accordance with published guidelines, with emphasis on titration of proven neuro-hormonal therapies for HF. Serial measurement of NT-proBNP testing was discouraged in the usual care group.

The primary endpoint was the composite of time-to-first HF hospitalization or cardiovascular mortality. The secondary endpoints were prespecified and included all-cause mortality, total hospitalizations for HF, days alive and not hospitalized for cardiovascular reasons, the individual components on the primary endpoint, and adverse events. A total sample size of 1,100 patients (550 per group) was expected to provide approximately 90% power to detect a difference in the primary endpoint with an assumed type I error rate of 0.05, 2-sided. The study investigators estimated that the annual event rate for the composite endpoint would be 40% in the usual care group. They targeted a 20% decrease in the primary endpoint at 12 months for the biomarker-guided group in the sample size calculation, based on the recognition that this treatment effect would be consistent with other effective HF therapies that have been incorporated into clinical practice.


A total of 894 patients (median age, 63 years; 286 [32%] women; median LVEF, 25%) with significantly elevated NT-proBNP (median, 2653 pg/ml) were enrolled. Follow-up was for a median of 15 months. The data and safety monitoring board recommended stopping the study for futility. The primary endpoint occurred in 37% (n = 164) of the patients in the biomarker-guided group and 37% (n = 164 patients) in the usual care group (adjusted hazard ratio [HR], 0.98; 95% confidence interval [CI], 0.79-1.22; p = 0.88). Cardiovascular mortality was 12% (n = 53) in the biomarker-guided group and 13% (n = 57) in the usual care group (HR, 0.94; 95% CI, 0.65-1.37; p = 0.75). None of the secondary endpoints or the decreases in the NT-proBNP levels achieved differed significantly between groups.


The authors concluded that a strategy of NT-proBNP–guided therapy in high-risk patients with systolic HF was not more effective than a usual care strategy in improving outcomes.


Acute or chronic decompensated HF is a heterogeneous condition with a varying degree of involvement of the heart, kidneys, lungs, and liver. As a result, management of acute HF remains a challenge. Moreover, the patients enrolled in this study had significantly elevated NT-proBNP, suggesting that HF was advanced (increasing the chances of comorbidities such as central sleep apnea), making it challenging to derive incremental benefit. Hopefully, a post-hoc analysis of this important study will allow better design of future clinical trials of acute HF.

Clinical Topics: Anticoagulation Management, Heart Failure and Cardiomyopathies, Acute Heart Failure, Chronic Heart Failure, Heart Failure and Cardiac Biomarkers, Sleep Apnea

Keywords: Biological Markers, Heart Failure, Hospitalization, Heart Failure, Systolic, Natriuretic Peptides, Natriuretic Peptide, Brain, Outcome Assessment (Health Care), Peptide Fragments, Sleep Apnea Syndromes, Stroke Volume

< Back to Listings