Neurohumoral Prediction of Benefit From Carvedilol in Ischemic Left Ventricular Dysfunction

Ovid Technologies (Wolters Kluwer Health) - Tập 99 Số 6 - Trang 786-792 - 1999
Mark Richards1, Robert N. Doughty2, M. Gary Nicholls3, Stephen MacMahon4, Hamid Ikram5, Norman Sharpe6, Eric A. Espiner7, Chris Frampton8, Timothy G. Yandle9
1A. M. Richards From the Department of Medicine, Christchurch Cardioendocrine Group, Christchurch School of Medicine, Christchurch, New Zealand.
2R. Doughty From the Department of Medicine, Christchurch Cardioendocrine Group, Christchurch School of Medicine, Christchurch, New Zealand.
3M. G. Nicholls From the Department of Medicine, Christchurch Cardioendocrine Group, Christchurch School of Medicine, Christchurch, New Zealand.
4S. Macmahon From the Department of Medicine, Christchurch Cardioendocrine Group, Christchurch School of Medicine, Christchurch, New Zealand.
5H. Ikram From the Department of Medicine, Christchurch Cardioendocrine Group, Christchurch School of Medicine, Christchurch, New Zealand.
6N. Sharpe From the Department of Medicine, Christchurch Cardioendocrine Group, Christchurch School of Medicine, Christchurch, New Zealand.
7E. A. Espiner From the Department of Medicine, Christchurch Cardioendocrine Group, Christchurch School of Medicine, Christchurch, New Zealand.
8C. Frampton From the Department of Medicine, Christchurch Cardioendocrine Group, Christchurch School of Medicine, Christchurch, New Zealand.
9T. G. Yandle From the Department of Medicine, Christchurch Cardioendocrine Group, Christchurch School of Medicine, Christchurch, New Zealand.

Tóm tắt

Background —Plasma neurohormones were analyzed for prediction of adverse outcomes and response to treatment in 415 patients with ischemic left ventricular dysfunction randomly assigned to receive carvedilol or placebo. Methods and Results —Atrial natriuretic peptide, brain natriuretic peptide (BNP), or norepinephrine (NE) levels above the group median were associated with increased mortality rates and heart failure. On multivariate analysis, both BNP and NE interacted with treatment to predict death or heart failure independent of age, New York Heart Association class, and left ventricular ejection fraction. For placebo, supramedian levels of BNP were associated with 3-fold the mortality rate of inframedian levels (20/104; 19% vs 6/99; 6%; P <0.01). For carvedilol, mortality rate was comparable in these 2 subgroups (12/109; 11% vs 8/94; 9%; NS). Corresponding rates for heart failure were 29/104 (28%) versus 3/99 (3%; P <0.001) for placebo and 16/109 (15%) versus 7/94 (7%; NS) for carvedilol. High NE levels did not predict additional benefit from carvedilol, which significantly reduced heart failure admissions only in those with NE levels below the median (13.1% to 4.0%; P <0.01). In the 23% of the study population with supramedian BNP but inframedian levels of NE, carvedilol reduced hospital admission with heart failure by >90% ( P <0.001). Conclusions —Carvedilol reduced mortality rates and heart failure in those with higher pretreatment BNP levels but lesser activation of plasma NE. Neurohumoral profiling may guide introduction of β-blockade in heart failure.

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Buckley MG, Sagnella GA, MacGregor GA. Stability of atrial natriuretic peptide during storage at −20°C. J Hum Hypertens. 1996;10:431–432.In 415 patients with ischemic left ventricular dysfunction, carvedilol reduced mortality rates (19.2% to 11.0%; P<0.05) and heart failure (27.9% to 14.7%; P<0.01) in those with supramedian brain natriuretic peptide (BNP) levels. In patients with inframedian norepinephrine levels, carvedilol reduced heart failure from 13.1% to 4.0% (P<0.01). In the subgroup (23%) with supramedian BNP but inframedian norepinephrine, carvedilol reduced heart failure admissions by >90% (P<0.001). Pretreatment neurohumoral profiling with plasma BNP and norepinephrine may identify patients who will benefit from carvedilol.