title: [Long-term outcome and tolerability of carvedilol therapy in Japanese patients with chronic heart failure].
abstract: OBJECTIVE
  Randomized controlled clinical studies in western countries have shown that the beta-blockers improve the survival of patients with chronic heart failure and are highly tolerable. The tolerability of beta-blocker therapy and the long-term prognosis for patients with chronic heart failure receiving beta-blockers remain unclear in Japan. In the present study, carvedilol was employed for the treatment of mild to severe chronic heart failure and the long-term prognosis of the patients was monitored to evaluate the tolerability and chronic efficacy of beta-blocker therapy in Japanese patients.
  
  
  METHODS
  Three hundred and twenty-seven patients with chronic heart failure [Classes II to IV according to the New York Heart Association (NYHA) classification] were studied. Carvedilol was started at a dose of 1.25 to 5 mg/day and then increased to the final target dose of 20 mg/day, depending on its tolerability in each patient. The patients were monitored with respect to their NYHA classification, daily mean heart rate (evaluated by Holter electrocardiography), changes of the plasma brain natriuretic peptide level, and prognosis. They were followed up for a mean period of 4.4 +/- 1.8 years.
  
  
  RESULTS
  Carvedilol was not tolerated by 21 of the 327 patients (6.4%), and was discontinued during the follow-up period in 38 patients (11.6%). The mean maintenance dose for the remaining 268 patients (82.0%), in whom treatment could be continued over the long term, was 14.1 +/- 7.5 mg. The NYHA classification and plasma brain natriuretic peptide level were significantly improved, and the daily mean heart rate was also significantly reduced in the 268 patients. Significant improvement was also observed in patients with severe heart failure (classes III or IV of the NYHA classification). The five-year survival rate of patients continuously treated with carvedilol was 83%, and their outcome was significantly better than that of those who could not tolerate the drug (49%; p < 0.001) or those who discontinued treatment prematurely (68%; p < 0.001). The treated group also had a significantly lower cardiac death rate than the intolerant group or discontinued group.
  
  
  CONCLUSIONS
  Carvedilol was well tolerated by Japanese patients with chronic heart failure. Treatment with low-dose carvedilol may improve the symptoms and prognosis of patients with mild to severe chronic heart failure over the long term.
authors.affiliation: Department of Cardiology, Tokyo Women's Medical University, Tokyo.
authors.forename: Naomi
authors.initials: N
authors.lastname: Kawashiro
authors.forename: Naoki
authors.initials: N
authors.lastname: Matsuda
authors.forename: Yoko
authors.initials: Y
authors.lastname: Endo
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Uchida
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kasanuki
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D044466:Asian People; D002227:Carbazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D000077261:Carvedilol; D004361:Drug Tolerance; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000188:drug therapy* / Q000401:mortality; D006339:Heart Rate; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D011379:Prognosis; D011412:Propanolamines / Q000008:administration & dosage / Q000627:therapeutic use*; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D020097:Natriuretic Peptide, Brain