Effect of Natriuretic Peptide–Guided Therapy on Hospitalization or Cardiovascular Mortality in High-Risk Patients With Heart Failure and Reduced Ejection Fraction

Abstract

IMPORTANCEThe natriuretic peptides 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. OBJECTIVE To determine whether an amino-terminal pro-B-type natriuretic peptide (NT-proBNP)-guided treatment strategy improves clinical outcomes vs usual care in high-risk patients with HF and reduced ejection fraction (HFrEF). DESIGN, SETTINGS, AND PARTICIPANTSThe Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure (GUIDE-IT) 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. This study planned to randomize 1100 patients with HFrEF (ejection fraction Յ40%), 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.INTERVENTIONS Patients were randomized to either an NT-proBNP-guided strategy or usual care. Patients randomized to the guided strategy (n = 446) had HF therapy titrated with the goal of achieving a target NT-proBNP of less than 1000 pg/mL. Patients randomized to usual care (n = 448) had HF care in accordance with published guidelines, with emphasis on titration of proven neurohormonal therapies for HF. Serial measurement of NT-proBNP testing was discouraged in the usual care group. MAIN OUTCOMES AND MEASURESThe primary end point was the composite of time-to-first HF hospitalization or cardiovascular mortality. Prespecified secondary end points included all-cause mortality, total hospitalizations for HF, days alive and not hospitalized for cardiovascular reasons, the individual components on the primary end point, and adverse events. RESULTSThe data and safety monitoring board recommended stopping the study for futility when 894 (median age, 63 years; 286 [32%] women) of the planned 1100 patients had been enrolled with follow-up for a median of 15 months. The primary end point occurred in 164 patients (37%) in the biomarker-guided group and 164 patients (37%) in the usual care group (adjusted hazard ratio [HR], 0.98; 95% CI, 0.79-1.22; P = .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 = .75). None of the secondary end points nor the decreases in the NT-proBNP levels achieved differed significantly between groups. CONCLUSIONS AND RELEVANCEIn high-risk patients with HFrEF, a strategy of NT-proBNPguided therapy was not more effective than a usual care strategy in improving outcomes.

Getting to Dry

“…Utility of a biomarker as a target for therapy requires not only clinical relevance, but also timely responsiveness to the therapy titration, and unique information beyond usual clinical assessments. Multiple trials have used natriuretic peptides as targets for adjustment of chronic outpatient therapy with neurohormonal antagonists [6][7][8][9][10] (Figure). When uptitration was aggressive in response to persistently high levels of natriuretic peptides, outcomes were better than without such uptitration.…”

Plasma cBIN1 Score (CS) Identifies HFrEF and Can Predict Cardiac Hospitalization in Stable Ambulatory Patients

“…For instance, it can be difficult to use natriuretic peptides to distinguish between those with severe HFrEF versus other volume overload states such as in chronic kidney disease. In a recent trial, use of NT-proBNP failed as a guide to medical management of HFrEF patients [16].…”

“…However, NT-proBNP assesses fluid status not muscle health and is less useful in the management of ambulatory patients with known HF [16]. Furthermore, renal dysfunction is associated with elevated concentrations of BNP markers [17] and BNP also has a negative correlation with body mass index (BMI) [18,19].…”

The year in cardiology 2017: heart failure

“…12 In the large and much anticipated Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure (GUIDE-IT) trial a strategy of aiming for an NT-proBNP <1000 ng/L vs. usual care did not reduce cardiovascular (CV) death or first or total HF hospitalizations, or even NT-proBNP levels. 13 In…”