Low-dose carvedilol improves left ventricular function and reduces cardiovascular hospitalization in Japanese patients with chronic heart failure: the Multicenter Carvedilol Heart Failure Dose Assessment (MUCHA) trial.
BACKGROUND
The efficacy and optimum dose of beta-blockers have not been established in Japanese patients with chronic heart failure (CHF). The efficacy and safety of two doses of carvedilol, a beta-blocker with vasodilator and antioxidant actions, were investigated in Japanese patients with CHF.


METHODS
After screening and a carvedilol challenge phase, 174 patients with mild to moderate CHF were randomly assigned (double-blinded) to placebo, 2.5 mg of carvedilol twice daily, or 10 mg of carvedilol twice daily. After a 2- to 4-week uptitration phase, maintenance treatment was continued for 24 to 48 weeks. The primary end point was improvement of the global assessment of CHF by the attending physician. Secondary end points were death or hospitalization for cardiovascular disease, cardiovascular hospitalization, hospitalization for heart failure, change of left ventricular ejection fraction, and change in New York Heart Association class.


RESULTS
Carvedilol therapy achieved dose-dependent improvement of all end points (P for linear trend, range.002 to <.001). Both carvedilol groups showed marked risk reduction (71% to 91%) for cardiovascular and CHF hospitalization and for death or cardiovascular hospitalization (P range,.024 to <.001 for pairwise comparisons with placebo). No significant differences were observed for noncardiovascular hospitalization or adverse events.


CONCLUSIONS
In Japanese patients with mild or moderate CHF, carvedilol achieved dose-related improvement of CHF and left ventricular ejection fraction; cardiovascular hospitalization was markedly reduced. At 5 mg/d, carvedilol conferred an important patient benefit, less than at 20 mg/d.
Hori
Masatsugu
M
Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Japan. mhori@medone.med.osaka-u.ac.jp
Sasayama
Shigetake
S
Kitabatake
Akira
A
Toyo-oka
Teruhiko
T
Handa
Shunnosuke
S
Yokoyama
Mitsuhiro
M
Matsuzaki
Masunori
M
Takeshita
Akira
A
Origasa
Hideki
H
Matsui
Kennichi
K
Hosoda
Saichi
S
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D000368:Aged; D002227:Carbazoles / Q000494:pharmacology / Q000627:therapeutic use*; D000077261:Carvedilol; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006333:Heart Failure / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D008875:Middle Aged; D011412:Propanolamines / Q000494:pharmacology / Q000627:therapeutic use*; D013318:Stroke Volume / Q000187:drug effects; D016019:Survival Analysis; D014665:Vasodilator Agents / Q000494:pharmacology / Q000627:therapeutic use; D016277:Ventricular Function, Left / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D014665:Vasodilator Agents; D000077261:Carvedilol