1. In this multicenter, randomized controlled study, the use of NT-proBNP levels to guide medical interventions for heart failure with reduced ejection fraction (HF-rEF) was non-superior to care as usual for cardiovascular-related hospitalizations and deaths.
2. Secondary endpoints, such as all-cause mortality, adverse events rates, and target NT-proBNP concentrations were also not significantly different between groups.
Evidence Rating Level: 1 (Excellent)
Study Rundown: During heart failure with reduced ejection fractions (HF-rEF), NT-proBNP rises with disease progression and falls with treatment, making it a potential marker to assess efficacy of medical interventions. However, smaller individual patient trials have not successfully uncovered a benefit for NT-proBNP guided therapy. In this multicenter, randomized clinical trial, patients with HF-rEF were recruited to either a NT-proBNP guided therapy group or care as usual with a median follow-up time of 15 months during a three year period. After 81% of the planned patients were enrolled, the trial was discontinued by an independent, NHLBI-run data safety monitoring board after meeting planned inefficacy criteria. At this time, patients in both groups had similar rates of hospitalization or death due to cardiovascular events, the primary endpoint. In addition, while HF-rEF patients had significantly more clinic visits, patients showed similar rates for all-cause mortality, cardiovascular mortality, HF hospitalization, all-cause hospitalizations, decrease in NT-proBNP over time, proportion of patients reaching the target NT-proBNP levels, and adverse events.
While the study authors noted that recruited patients in both groups had more severe HF-rEF than in other trials, it seems likely that NT-proBNP guided therapy offers little benefit over care as usual.
In-Depth [randomized controlled trial]: A total of 894 patients with HF-rEF over 45 trial sites in the US and Canada were enrolled to this randomized controlled trial from January 2013 to July 2016. Patients had chronic HF-rEF with an ejection fraction <40%, an HF event within the last 12 months, and NT-proBNP levels over 2000 pg/mL in the last 30 days with no history of acute coronary syndrome or revascularization procedure within 30 days, cardiac resynchronization within 3 months, end-stage renal disease, or anticipated heart transplant or mechanical cardiac support within the next 12 months. In July of 2016, the independent, NHLBI-run safety and monitoring board discontinued the study after inefficacy criteria were reached (81% of planned patients enrolled). The NT-proBNP group was similar to the care as usual group in terms of hospitalization or death due to cardiovascular events (treatment difference = −2.2%;CI95 −9.1% to 4.6%). The adjusted hazard ratio (HR) for all-cause mortality was also similar between groups (0.86; CI95 0.62-1.20; p = 0.37). In addition, cardiovascular mortality, HF hospitalization, all-cause hospitalizations, decrease in NT-proBNP over time, proportion of patients reach the target NT-proBNP levels, and adverse events rates were all similar between groups (p > 0.05). As may be predicted, the rate of clinic visits was significantly greater for the NT-proBNP group (Wilcoxon p = 0.002) with more adjustments to HF therapy (Wilcoxon p < 0.001).
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