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J Am Coll Cardiol, 2001; 37:1781-1787
© 2001 by the American College of Cardiology Foundation
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CLINICAL STUDY: HEART FAILURE

Plasma N-terminal pro-brain natriuretic peptide and adrenomedullin

Prognostic utility and prediction of benefit from carvedilol in chronic ischemic left ventricular dysfunction

A. Mark Richards, MD, PhDa, Robert Doughty, MD{dagger}, M. Gary Nicholls, MDa{dagger} {ddagger} §, Stephen MacMahon, PhD§, Norman Sharpe, MD{dagger}, Judy Murphy, RN{ddagger}, Eric A. Espiner, MDa, Christopher Frampton, PhDa, Timothy G. Yandle, PhDa for the Australia-New Zealand Heart Failure Group

a Department of Medicine, Christchurch Hospital, Christchurch, New Zealand
{dagger} Department of Medicine, Auckland, New Zealand
{ddagger} Clinical Trials Research Unit, University of Auckland, Auckland, New Zealand
§ Institute for International Health, Sydney, Australia

Manuscript received October 10, 2000; revised manuscript received February 15, 2001, accepted February 26, 2001.

Reprint requests and correspondence: Prof. A. Mark Richards, Department of Medicine, Christchurch Hospital, Riccarton Avenue, P.O. Box 4345, Christchurch 8001, New Zealand.
barbara.griffin{at}chmeds.ac.nz

OBJECTIVES

We sought to assess plasma concentrations of the amino (N)-terminal portion of pro-brain natriuretic peptide (N-BNP) and adrenomedullin for prediction of adverse outcomes and responses to treatment in 297 patients with ischemic left ventricular (LV) dysfunction who were randomly assigned to receive carvedilol or placebo.

BACKGROUND

Although neurohormonal status has known prognostic significance in heart failure, the predictive power of either N-BNP or adrenomedullin in chronic ischemic LV dysfunction has not been previously reported.

METHODS

Plasma N-BNP and adrenomedullin were measured in 297 patients with chronic ischemic (LV) dysfunction before randomization to carvedilol or placebo, added to established treatment with a converting enzyme inhibitor and loop diuretic (with or without digoxin). The patients’ clinical outcomes, including mortality and heart failure events, were recorded for 18 months.

RESULTS

Above-median N-BNP and adrenomedullin levels conferred increased risks (all p < 0.001) of mortality (risk ratios [95% confidence intervals]: 4.67 [2–10.9] and 3.92 [1.76–8.7], respectively) and hospital admission with heart failure (4.7 [2.2–10.3] and 2.4 [1.3–4.5], respectively). Both of these predicted death or heart failure independent of age, New York Heart Association functional class, LV ejection fraction, previous myocardial infarction or previous admission with heart failure. Carvedilol reduced the risk of death or heart failure in patients with above-median levels of N-BNP or adrenomedullin, or both, to rates not significantly different from those observed in patients with levels below the median value.

CONCLUSIONS

In patients with established ischemic LV dysfunction, plasma N-BNP and adrenomedullin are independent predictors of mortality and heart failure. Carvedilol reduced mortality and heart failure in patients with higher pre-treatment plasma N-BNP and adrenomedullin.

Abbreviations and Acronyms
  ACE = angiotensin-converting enzyme
  ANP = atrial natriuretic peptide
  BNP = brain natriuretic peptide
  CHF = congestive heart failure
  CI = confidence interval
  LV = left ventricular
  LVEF = left ventricular ejection fraction
  MI = myocardial infarction
  N-BNP = amino (N)-terminal pro-brain natriuretic peptide
  NYHA = New York Heart Association
  RR = risk ratio




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