title: Carvedilol produces dose-related improvements in left ventricular function and survival in subjects with chronic heart failure. MOCHA Investigators.
abstract: BACKGROUND
  We conducted a multicenter, placebo-controlled trial designed to establish the efficacy and safety of carvedilol, a "third-generation" beta -blocking agent with vasodilator properties, in chronic heart failure.
  
  
  RESULTS
  Three hundred forty-five subjects with mild to moderate, stable chronic heart failure were randomized to receive treatment with placebo, 6.25 mg BID carvedilol (low-dose group), 12.5 mg BID carvedilol (medium-dose group), or 25 mg BID carvedilol (high-dose group). After a 2- to 4-week up-titration period, subjects remained on study medication for a period of 6 months. The primary efficacy parameter was submaximal exercise measured by two different techniques, the 6-minute corridor walk test and the 9-minute self-powered treadmill test. Carvedilol had no detectable effect on submaximal exercise as measured by either technique. However, carvedilol was associated with dose-related improvements in LV function (by 5, 6, and 8 ejection fraction [EF] units in the low-, medium-, and high-dose carvedilol groups, respectively, compared with 2 EF units with placebo, P < .001 for linear dose response) and survival (respective crude mortality rates of 6.0%, 6.7%, and 1.1% with increasing doses of carvedilol compared with 15.5% in the placebo group, P < .001). When the three carvedilol groups were combined, the all-cause actuarial mortality risk was lowered by 73% in carvedilol-treated subjects (P < .001). Carvedilol also lowered the hospitalization rate (by 58% to 64%, P = .01) and was generally well tolerated.
  
  
  CONCLUSIONS
  In subjects with mild to moderate heart failure from systolic dysfunction, carvedilol produced dose-related improvements in LV function and dose-related reductions in mortality and hospitalization rate.
authors.affiliation: Division of Cardiology, University of Colorado HSC, Denver 80262, USA. michael.bristow@uchsc.edu
authors.forename: M R
authors.initials: MR
authors.lastname: Bristow
authors.forename: E M
authors.initials: EM
authors.lastname: Gilbert
authors.forename: W T
authors.initials: WT
authors.lastname: Abraham
authors.forename: K F
authors.initials: KF
authors.lastname: Adams
authors.forename: M B
authors.initials: MB
authors.lastname: Fowler
authors.forename: R E
authors.initials: RE
authors.lastname: Hershberger
authors.forename: S H
authors.initials: SH
authors.lastname: Kubo
authors.forename: K A
authors.initials: KA
authors.lastname: Narahara
authors.forename: H
authors.initials: H
authors.lastname: Ingersoll
authors.forename: S
authors.initials: S
authors.lastname: Krueger
authors.forename: S
authors.initials: S
authors.lastname: Young
authors.forename: N
authors.initials: N
authors.lastname: Shusterman
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D002227:Carbazoles / Q000009:adverse effects / Q000627:therapeutic use*; D002303:Cardiac Output, Low / Q000188:drug therapy* / Q000401:mortality* / Q000503:physiopathology; D000077261:Carvedilol; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006760:Hospitalization; D006801:Humans; D008297:Male; D008875:Middle Aged; D011412:Propanolamines / Q000009:adverse effects / Q000627:therapeutic use*; D011788:Quality of Life; D016019:Survival Analysis; D016277:Ventricular Function, Left / Q000187:drug effects*
chemical_list: D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol