No abstract

Introduction: Older age is independently associated with greater NT-proBNP levels. As such, the aim of this study was to establish the influence of age on serial NT-proBNP levels over time and the impact of age on response to natriuretic peptide-guided therapy (NPGT) versus usual care for heart failure with reduced ejection fraction (HFrEF). Hypothesis: Age will modify the effect of NPGT on serial NT-proBNP in patients with HFrEF. Methods: Using data from GUIDE-IT, the impact of age on the association of NPGT with serial NT-proBNP and long-term outcomes was assessed. Time-to-event analyses and generalized linear mixed modeling were used to evaluate the effect of age, by quartile, on long-term outcomes and serial NT-proBNP by randomized treatment (NPGT vs. usual care), respectively. Results: In this cohort (N=893), the median age was 63 [range 21-90, IQR 53-71] years and was 32% female and 36% black race. Age was modestly correlated with NT-proBNP (Spearman rho 0.34, p<0.001). At baseline, older age was associated with lower doses of ACEI/ARB (p-trend 0.019) and aldosterone antagonist use (p-trend<0.001), but not beta-blocker use (p=0.06). Older age was associated with a greater risk of all-cause death (log-rank, p<0.001) but not associated with a greater risk of combined CV death or HF hospitalization (log-rank, P=0.56). Although older age was associated with greater NT-proBNP levels over time (Q4 vs. Q1 beta 2.1 x pg/mL/days, p<0.001), it did not modify the association of NPGT on serial NT-proBNP ( Figure, Q4, Q3, and Q2 vs. Q1 by treatment arm, p-interaction>0.09 for all). Age also did not modify the impact of NPGT on either mortality or the composite, CV death or HF hospitalization (P-interaction>0.05 for both). Conclusions: Older age was associated with greater NT-proBNP levels. However, age did not modify the association of NPGT on clinical outcomes or serial NT-proBNP. These data do not support the hypothesis that age modifies the NT-proBNP response to HFrEF treatments.