title: Double-blind, placebo-controlled study of the effects of carvedilol in patients with moderate to severe heart failure. The PRECISE Trial. Prospective Randomized Evaluation of Carvedilol on Symptoms and Exercise.
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.
  
  
  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 < or = 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.
authors.affiliation: College of Physicians and Surgeons, Columbia University, New York, NY, USA.
authors.forename: M
authors.initials: M
authors.lastname: Packer
authors.forename: W S
authors.initials: WS
authors.lastname: Colucci
authors.forename: J D
authors.initials: JD
authors.lastname: Sackner-Bernstein
authors.forename: C S
authors.initials: CS
authors.lastname: Liang
authors.forename: D A
authors.initials: DA
authors.lastname: Goldscher
authors.forename: I
authors.initials: I
authors.lastname: Freeman
authors.forename: M L
authors.initials: ML
authors.lastname: Kukin
authors.forename: V
authors.initials: V
authors.lastname: Kinhal
authors.forename: J E
authors.initials: JE
authors.lastname: Udelson
authors.forename: M
authors.initials: M
authors.lastname: Klapholz
authors.forename: S S
authors.initials: SS
authors.lastname: Gottlieb
authors.forename: D
authors.initials: D
authors.lastname: Pearle
authors.forename: R J
authors.initials: RJ
authors.lastname: Cody
authors.forename: J J
authors.initials: JJ
authors.lastname: Gregory
authors.forename: N E
authors.initials: NE
authors.lastname: Kantrowitz
authors.forename: T H
authors.initials: TH
authors.lastname: LeJemtel
authors.forename: S T
authors.initials: ST
authors.lastname: Young
authors.forename: M A
authors.initials: MA
authors.lastname: Lukas
authors.forename: N H
authors.initials: NH
authors.lastname: Shusterman
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D000368:Aged; D002227:Carbazoles / Q000009:adverse effects / Q000627:therapeutic use*; D002303:Cardiac Output, Low / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D000077261:Carvedilol; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009017:Morbidity; D010919:Placebos; D011412:Propanolamines / Q000009:adverse effects / Q000627:therapeutic use*; D012307:Risk Factors; D012720:Severity of Illness Index; D013318:Stroke Volume / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D010919:Placebos; D011412:Propanolamines; D000077261:Carvedilol