Double-blind, placebo-controlled study of the effects of carvedilol in patients with moderate to severe heart failure

The PRECISE Trial

Milton Packer, Wilson S. Colucci, Jonathan D. Sackner-Bernstein, Chang Seng Liang, David A. Goldscher, Israel Freeman, Marrick L. Kukin, Vithal Kinhal, James E. Udelson, Marc Klapholz, Stephen S. Gottlieb, David Pearle, Robert J. Cody, John J. Gregory, Nikki E. Kantrowitz, Thierry H. LeJemtel, Sarah T. Young, Mary Ann Lukas, Neil H. Shusterman

Research output: Contribution to journalArticle

547 Citations (Scopus)

Abstract

Background: Carvedilol has improved the symptomatic status of patients with moderate to severe heart failure in single-center studies, but its clinical effects have not been evaluated in large, multicenter trials. Methods and Results: We enrolled 278 patients with moderate to severe heart failure (6-minute walk distance, 150 to 450 m) and a left ventricular ejection fraction ≤0.35 at 31 centers. After an open-label, run-in period, each patient was randomly assigned (double-blind) to either placebo (n=145) or carvedilol (n=133; target dose, 25 to 50 mg BID) for 6 months, while background therapy with digoxin, diuretics, and an ACE inhibitor remained constant. Compared with placebo, patients in the carvedilol group had a greater frequency of symptomatic improvement and lower risk of clinical deterioration, as evaluated by changes in the NYHA functional class (P=.014) or by a global assessment of progress judged either by the patient (P=.002) or by the physician (P<.001). In addition, treatment with carvedilol was associated with a significant increase in ejection fraction (P<.001) and a significant decrease in the combined risk of morbidity and mortality (P=.029). In contrast, carvedilol therapy had little effect on indirect measures of patient benefit, including changes in exercise tolerance or quality-of-life scores. The effects of the drug were similar in patients with ischemic heart disease or idiopathic dilated cardiomyopathy as the cause of heart failure. Conclusions: These findings indicate that, in addition to its favorable effects on survival, carvedilol produces important clinical benefits in patients with moderate to severe heart failure treated with digoxin, diuretics, and an ACE inhibitor.

Original languageEnglish (US)
Pages (from-to)2793-2799
Number of pages7
JournalCirculation
Volume94
Issue number11
StatePublished - 1996

Fingerprint

Heart Failure
Placebos
Digoxin
Angiotensin-Converting Enzyme Inhibitors
Diuretics
Exercise Tolerance
carvedilol
Dilated Cardiomyopathy
Stroke Volume
Multicenter Studies
Myocardial Ischemia
Therapeutics
Quality of Life
Morbidity
Physicians
Survival
Mortality
Pharmaceutical Preparations

Keywords

  • blockers, beta-adrenergic
  • carvedilol
  • heart failure

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Packer, M., Colucci, W. S., Sackner-Bernstein, J. D., Liang, C. S., Goldscher, D. A., Freeman, I., ... Shusterman, N. H. (1996). Double-blind, placebo-controlled study of the effects of carvedilol in patients with moderate to severe heart failure: The PRECISE Trial. Circulation, 94(11), 2793-2799.

Double-blind, placebo-controlled study of the effects of carvedilol in patients with moderate to severe heart failure : The PRECISE Trial. / Packer, Milton; Colucci, Wilson S.; Sackner-Bernstein, Jonathan D.; Liang, Chang Seng; Goldscher, David A.; Freeman, Israel; Kukin, Marrick L.; Kinhal, Vithal; Udelson, James E.; Klapholz, Marc; Gottlieb, Stephen S.; Pearle, David; Cody, Robert J.; Gregory, John J.; Kantrowitz, Nikki E.; LeJemtel, Thierry H.; Young, Sarah T.; Lukas, Mary Ann; Shusterman, Neil H.

In: Circulation, Vol. 94, No. 11, 1996, p. 2793-2799.

Research output: Contribution to journalArticle

Packer, M, Colucci, WS, Sackner-Bernstein, JD, Liang, CS, Goldscher, DA, Freeman, I, Kukin, ML, Kinhal, V, Udelson, JE, Klapholz, M, Gottlieb, SS, Pearle, D, Cody, RJ, Gregory, JJ, Kantrowitz, NE, LeJemtel, TH, Young, ST, Lukas, MA & Shusterman, NH 1996, 'Double-blind, placebo-controlled study of the effects of carvedilol in patients with moderate to severe heart failure: The PRECISE Trial', Circulation, vol. 94, no. 11, pp. 2793-2799.
Packer M, Colucci WS, Sackner-Bernstein JD, Liang CS, Goldscher DA, Freeman I et al. Double-blind, placebo-controlled study of the effects of carvedilol in patients with moderate to severe heart failure: The PRECISE Trial. Circulation. 1996;94(11):2793-2799.
Packer, Milton ; Colucci, Wilson S. ; Sackner-Bernstein, Jonathan D. ; Liang, Chang Seng ; Goldscher, David A. ; Freeman, Israel ; Kukin, Marrick L. ; Kinhal, Vithal ; Udelson, James E. ; Klapholz, Marc ; Gottlieb, Stephen S. ; Pearle, David ; Cody, Robert J. ; Gregory, John J. ; Kantrowitz, Nikki E. ; LeJemtel, Thierry H. ; Young, Sarah T. ; Lukas, Mary Ann ; Shusterman, Neil H. / Double-blind, placebo-controlled study of the effects of carvedilol in patients with moderate to severe heart failure : The PRECISE Trial. In: Circulation. 1996 ; Vol. 94, No. 11. pp. 2793-2799.
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abstract = "Background: Carvedilol has improved the symptomatic status of patients with moderate to severe heart failure in single-center studies, but its clinical effects have not been evaluated in large, multicenter trials. Methods and Results: We enrolled 278 patients with moderate to severe heart failure (6-minute walk distance, 150 to 450 m) and a left ventricular ejection fraction ≤0.35 at 31 centers. After an open-label, run-in period, each patient was randomly assigned (double-blind) to either placebo (n=145) or carvedilol (n=133; target dose, 25 to 50 mg BID) for 6 months, while background therapy with digoxin, diuretics, and an ACE inhibitor remained constant. Compared with placebo, patients in the carvedilol group had a greater frequency of symptomatic improvement and lower risk of clinical deterioration, as evaluated by changes in the NYHA functional class (P=.014) or by a global assessment of progress judged either by the patient (P=.002) or by the physician (P<.001). In addition, treatment with carvedilol was associated with a significant increase in ejection fraction (P<.001) and a significant decrease in the combined risk of morbidity and mortality (P=.029). In contrast, carvedilol therapy had little effect on indirect measures of patient benefit, including changes in exercise tolerance or quality-of-life scores. The effects of the drug were similar in patients with ischemic heart disease or idiopathic dilated cardiomyopathy as the cause of heart failure. Conclusions: These findings indicate that, in addition to its favorable effects on survival, carvedilol produces important clinical benefits in patients with moderate to severe heart failure treated with digoxin, diuretics, and an ACE inhibitor.",
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T1 - Double-blind, placebo-controlled study of the effects of carvedilol in patients with moderate to severe heart failure

T2 - The PRECISE Trial

AU - Packer, Milton

AU - Colucci, Wilson S.

AU - Sackner-Bernstein, Jonathan D.

AU - Liang, Chang Seng

AU - Goldscher, David A.

AU - Freeman, Israel

AU - Kukin, Marrick L.

AU - Kinhal, Vithal

AU - Udelson, James E.

AU - Klapholz, Marc

AU - Gottlieb, Stephen S.

AU - Pearle, David

AU - Cody, Robert J.

AU - Gregory, John J.

AU - Kantrowitz, Nikki E.

AU - LeJemtel, Thierry H.

AU - Young, Sarah T.

AU - Lukas, Mary Ann

AU - Shusterman, Neil H.

PY - 1996

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N2 - Background: Carvedilol has improved the symptomatic status of patients with moderate to severe heart failure in single-center studies, but its clinical effects have not been evaluated in large, multicenter trials. Methods and Results: We enrolled 278 patients with moderate to severe heart failure (6-minute walk distance, 150 to 450 m) and a left ventricular ejection fraction ≤0.35 at 31 centers. After an open-label, run-in period, each patient was randomly assigned (double-blind) to either placebo (n=145) or carvedilol (n=133; target dose, 25 to 50 mg BID) for 6 months, while background therapy with digoxin, diuretics, and an ACE inhibitor remained constant. Compared with placebo, patients in the carvedilol group had a greater frequency of symptomatic improvement and lower risk of clinical deterioration, as evaluated by changes in the NYHA functional class (P=.014) or by a global assessment of progress judged either by the patient (P=.002) or by the physician (P<.001). In addition, treatment with carvedilol was associated with a significant increase in ejection fraction (P<.001) and a significant decrease in the combined risk of morbidity and mortality (P=.029). In contrast, carvedilol therapy had little effect on indirect measures of patient benefit, including changes in exercise tolerance or quality-of-life scores. The effects of the drug were similar in patients with ischemic heart disease or idiopathic dilated cardiomyopathy as the cause of heart failure. Conclusions: These findings indicate that, in addition to its favorable effects on survival, carvedilol produces important clinical benefits in patients with moderate to severe heart failure treated with digoxin, diuretics, and an ACE inhibitor.

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