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.
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.


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.
Hartmann
Franz
F
Medizinische Klinik II, Universitaetsklinikum Schleswig-Holstein, Campus Luebeck, Ratzeburger Allee 160, D-23538 Luebeck, Germany. hartmann@medinf.mu-luebeck.de
Packer
Milton
M
Coats
Andrew J S
AJ
Fowler
Michael B
MB
Krum
Henry
H
Mohacsi
Paul
P
Rouleau
Jean L
JL
Tendera
Michal
M
Castaigne
Alain
A
Anker
Stefan D
SD
Amann-Zalan
Ildiko
I
Hoersch
Silke
S
Katus
Hugo A
HA
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000368:Aged; D015415:Biomarkers; D001794:Blood Pressure; D002227:Carbazoles / Q000627:therapeutic use; D002317:Cardiovascular Agents / Q000627:therapeutic use; D000077261:Carvedilol; D003404:Creatinine / Q000097:blood; D004359:Drug Therapy, Combination; D005060:Europe / Q000453:epidemiology; D005260:Female; D006333:Heart Failure / Q000097:blood* / Q000209:etiology / Q000401:mortality; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D015993:Life Tables; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000150:complications; D020097:Natriuretic Peptide, Brain; D009419:Nerve Tissue Proteins / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D011237:Predictive Value of Tests; D011379:Prognosis; D011412:Propanolamines / Q000627:therapeutic use; D016016:Proportional Hazards Models; D011446:Prospective Studies; D013318:Stroke Volume; D016019:Survival Analysis
D000319:Adrenergic beta-Antagonists; D015415:Biomarkers; D002227:Carbazoles; D002317:Cardiovascular Agents; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D011412:Propanolamines; C109794:pro-brain natriuretic peptide (1-76); D000077261:Carvedilol; D020097:Natriuretic Peptide, Brain; D003404:Creatinine