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

Anand, I. S. et al. (2011) 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. Circulation: Heart Failure, 4(5), pp. 569-577. (doi:10.1161/CIRCHEARTFAILURE.111.962654) (PMID:21715583)

Full text not currently available from Enlighten.

Abstract

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<0.001); all-cause mortality (adjusted HR, 2.04; 95% CI, 1.68 to 2.47; P<0.001); and a composite of HF events, including death due to worsening HF or sudden death or hospitalization due to worsening HF (adjusted HR, 1.77; 95% CI, 1.43 to 2.20; P<0.001). There were significant interactions between the effect of irbesartan and median split of baseline NT-proBNP for the primary outcome (P=0.005), all-cause mortality (P=0.05), and the HF composite outcome (P<0.001). Use of irbesartan was associated with improved outcomes in patients with NT-proBNP below, but not above, the median. After adjusting for 20 baseline covariates, irbesartan still had a beneficial effect on the primary outcome (HR, 0.74; 95% CI, 0.60 to 90; 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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Cleland, Professor John and McMurray, Professor John
Authors: Anand, I. S., Rector, T. S., Cleland, J. G., Kuskowski, M., McKelvie, R. S., Persson, H., McMurray, J. J., Zile, M. R., Komajda, M., Massie, B. M., and Carson, P. E.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Robertson Centre
Journal Name:Circulation: Heart Failure
Publisher:Lippincott Williams and Wilkins
ISSN:1941-3289
ISSN (Online):1941-3297
Published Online:29 June 2011

University Staff: Request a correction | Enlighten Editors: Update this record