Differences in NT-proBNP Response and Prognosis in Men and Women With Heart Failure With Reduced Ejection Fraction

Abstract

Background NT-proBNP (N-terminal pro-B-type natriuretic peptide) is a prognostic biomarker in heart failure (HF) with reduced ejection fraction. However, it is unclear whether there is a sex difference in NT-proBNP response and whether the therapeutic goal of NT-proBNP ≤1000 pg/mL has equivalent prognostic value in men and women with HF with reduced ejection fraction. Methods and Results In a secondary analysis of the GUIDE-IT (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment) trial we analyzed trends in NT-proBNP and goal attainment by sex. Differences in clinical characteristics, HF treatment, and time to all-cause death or HF hospitalization were compared. Landmark analysis at 3 months determined the prognostic value of early NT-proBNP goal achievement in men and women. Of the 286 (32%) women and 608 (68%) men in the GUIDE-IT trial, women were more likely to have a nonischemic cause and shorter duration of HF. Guideline-directed medical therapy was less intense over time in women. The absolute NT-proBNP values were consistently lower in women; however, the change in NT-proBNP and clinical outcomes were similar. After adjustment, women achieving the NT-proBNP goal had an 82% reduction in death or HF hospitalization compared with a 59% reduction in men. Conclusions Men and women with HF with reduced ejection fraction had a similar NT-proBNP response despite less intensive HF treatment among women. However, compared with men, the early NT-proBNP goal of ≤1000 pg/mL had greater prognostic value in women. Future efforts should be aimed at intensifying guideline-directed medical therapy in women, which may result in greater NT-proBNP reductions and improved outcomes in women with HF with reduced ejection fraction. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01685840.

Keywords: N‐terminal pro‐B‐type natriuretic peptide; heart failure; women.

Conflict of interest statement

Drs O'Connor and Felker have received grant support from the National Institutes of Health. Drs Cooper, Leifer, and Desvigne‐Nickens are employees of the National Heart, Lung, and Blood Institute and were members of the GUIDE‐IT Steering Committee. Dr Januzzi is a trustee of the American College of Cardiology; has received grant support from Novartis Pharmaceuticals, Innolife, Applied Therapeutics, and Abbott Diagnostics, and consulting income from Abbott, Janssen, Novartis, Pfizer, Merck, and Roche Diagnostics; and participates in clinical end point committees/data safety monitoring boards for Abbott, AbbVie, Amgen, Bayer, CVRx, and Takeda. The remaining authors have no disclosures to report.

Figures

Figure 1. CONSORT diagram.

Study flow diagram of secondary analysis population and subgroup. GUIDE‐IT indicates Guiding Evidence Based Therapy Using Biomarker Intensified Treatment; and NT‐proBNP, N‐terminal pro‐B‐type natriuretic peptide.

Figure 2. Sex differences in target dosing of guideline‐directed medical therapy (GDMT) at 1 year.

Pie charts indicating the proportion of men and women achieving target doses of β‐blocker therapy (top row) and angiotensin‐converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) therapy (bottom row) at 1 year. Men were significantly more likely to be at or above target doses than women. *P=0.003; †P=0.08. NT‐proBNP indicates N‐terminal pro‐B‐type natriuretic peptide.

Figure 3. Reasons for not titrating medications by sex.

Bar graph indicating the reasons for not titrating medication dose in men and women. NT‐proBNP indicates N‐terminal pro‐B‐type natriuretic peptide.

Figure 4. Change in NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) in men and women with heart failure with reduced ejection fraction.

The trend in NT‐proBNP was similar between men and women. Dots are median NT‐proBNP (pg/mL); whiskers are interquartile range.

Figure 5. Clinical outcomes in men and women with heart failure (HF) with reduced ejection fraction.

The Kaplan‐Meier curves for the primary outcome of death or HF hospitalization (upper left) and secondary outcomes of death (upper right); HF hospitalization (lower left) and cardiovascular hospitalization (lower right). Clinical outcomes were similar in men and women.

Figure 6. Clinical outcomes in men and women by early NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) goal achievement.

Clinical outcomes were similar between men and women not achieving the early NT‐proBNP goal (blue and red dashed lines). However, separation of the solid curves suggests a trend towards fewer events among women achieving the early NT‐proBNP goal compared with men achieving the early NT‐proBNP goal.