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(Circulation. 2004;110:1780-1786.)
© 2004 American Heart Association, Inc.

Heart Failure

Prognostic Impact of Plasma N-Terminal Pro–Brain Natriuretic Peptide in Severe Chronic Congestive Heart Failure

A Substudy of the Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) Trial

Franz Hartmann, MD; Milton Packer, MD; Andrew J.S. Coats, MD; Michael B. Fowler, MD; Henry Krum, MB, BS, PhD; Paul Mohacsi, MD; Jean L. Rouleau, MD; Michal Tendera, MD; Alain Castaigne, MD; Stefan D. Anker, MD; Ildiko Amann-Zalan, MD, PhD; Silke Hoersch, PhD; Hugo A. Katus, MD

From Medizinische Klinik II, Universitaetsklinikum Schleswig-Holstein, Campus Luebeck, Luebeck (F.H.); Carvedilol Prospective Randomized Cumulative Survival Study Group (M.P., A.J.S.C., M.B.F., H.K., P.M., J.L.R., M.T., A.C.); Applied Cachexia Research, Department of Cardiology, Charite, Campus Virchow-Klinikum, Berlin (S.D.A.); Roche Diagnostics GmbH Mannheim (I.A.-Z.); Koehler GmbH, Freiburg (S.H.); and Innere Medizin III, Medizinische Universitätsklinik Heidelberg, Heidelberg (H.A.K.), Germany.

Correspondence to Dr F. Hartmann, Medizinische Klinik II, Universitaetsklinikum Schleswig-Holstein, Campus Luebeck, Ratzeburger Allee 160, D-23538 Luebeck, Germany. E-mail hartmann{at}medinf.mu-luebeck.de

Received June 26, 2002; de novo received October 25, 2003; revision received May 12, 2004; accepted May 21, 2004.

Background— The utility of N-terminal proBNP (NT-proBNP) to predict the occurrence of death and hospitalization was prospectively evaluated in the COPERNICUS study, which enrolled patients with an ejection fraction <25% and symptoms of chronic congestive heart failure at rest or on minimal exertion.

Methods and Results— Baseline plasma concentrations of NT-proBNP were measured in a subgroup of 814 men and 197 women with symptoms at rest or on minimal exertion who were enrolled in the COPERNICUS study and were randomized to placebo (n=506) or carvedilol (n=505). Values of NT-proBNP were markedly increased despite the requirement that patients be euvolemic before the start of treatment (mean±SD, 3235±4392 pg/mL; median, 1767 pg/mL). By univariate Cox regression analysis, NT-proBNP was found to be a powerful predictor of subsequent all-cause mortality (relative risk [RR], 2.7; 95% CI, 1.7 to 4.3; P=0.0001 for above versus below median) and all-cause mortality or hospitalization for heart failure (RR, 2.4; 95% CI, 1.8 to 3.4; P=0.0001 for above versus below median). The predictive value of NT-proBNP was similar when both placebo and carvedilol patients were analyzed separately. No significant interaction was found between NT-proBNP and treatment group (P=0.93 for above- versus below-median NT-proBNP).

Conclusions— NT-proBNP was consistently associated with increased risk for all-cause mortality and for all-cause mortality or hospitalization for heart failure in patients with severe congestive heart failure, even in those who were clinically euvolemic. This marker therefore may be a useful tool in risk stratification of patients with severe congestive heart failure.

Key Words: heart failure • natriuretic peptides • prognosis

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