Prognostic value of baseline plasma amino-terminal pro-brain natriuretic peptide and its interactions with irbesartan treatment effects in patients with heart failure and preserved ejection fraction: findings from the I-PRESERVE trial

Background— Plasma concentrations of natriuretic peptides (NPs) are associated with morbidity and mortality in patients with systolic heart failure (HF). However, the role of NP as a prognostic marker in patients with HF and preserved ejection fraction (HFpEF) has not been studied in a large cohort of well-characterized patients. Moreover, it is unclear whether treatments have a differential effect on morbidity and mortality across the spectrum of NP levels. Methods and Results— N-terminal pro-brain natriuretic peptide (NT-proBNP) was measured at baseline in 3480 patients in the I-PRESERVE (Irbesartan in Heart Failure with Preserved Ejection Fraction Trial). In a multivariable Cox regression model, NT-proBNP above the median of 339 pg/mL was independently associated with an increased risk of the primary end point of all-cause mortality and prespecified cardiovascular hospitalizations (adjusted hazard ratio [HR], 1.79; 95% CI, 1.56 to 2.10; P P P P =0.005), all-cause mortality ( P =0.05), and the HF composite outcome ( P P =0.003), all-cause mortality (HR, 0.75; 95% CI, 0.56 to 0.99; P =0.046), and HF composite outcome (HR, 0.57; 95% CI, 0.41 to 0.80; P =0.001) in patients with NT-proBNP below the median. Conclusions— The unexpected benefit of irbesartan in lower-risk patients with HFpEF in this post hoc analysis may indicate effects on early, but not later, high-risk stages of the disease. These findings question the strategy of using elevated plasma concentrations of NP as a patient selection criterion in HFpEF trials. More studies are needed to support or contest this practice. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00095238.