title: Tolerability and efficacy of carvedilol in patients with New York Heart Association class IV heart failure.
abstract: OBJECTIVE
  The purpose of this study was to assess the tolerability and efficacy of carvedilol in patients with New York Heart Association (NYHA) functional class IV symptoms.
  
  
  BACKGROUND
  Carvedilol, a nonselective beta-adrenergic blocking drug with alpha-adrenergic blocking and antioxidant properties, has been shown to improve left ventricular function and clinical outcome in patients with mild to moderate chronic heart failure.
  
  
  METHODS
  We retrospectively analyzed the outcomes of 230 patients with heart failure treated with carvedilol who were stratified according to baseline functional class: 63 patients were NYHA class IV and 167 were NYHA class I, II or III. Carvedilol was commenced at 3.125 mg b.i.d. and titrated to 25 mg b.i.d. as tolerated. Patients with class IV symptoms were older (p = 0.03), had lower left ventricular fractional shortening (p < 0.001), had lower six-min walk distance (p < 0.001) and were receiving more heart failure medications at baseline compared with less symptomatic patients.
  
  
  RESULTS
  Nonfatal adverse events while taking carvedilol occurred more frequently in class IV patients (43% vs. 24%, p < 0.0001), and more often resulted in permanent withdrawal of the drug (25% vs. 13%, p < 0.01). Thirty-seven (59%) patients who were NYHA class IV at baseline had improved by one or more functional class at 3 months, 8 (13%) were unchanged and 18 (29%) had deteriorated or died. Among the less symptomatic group, 62 (37%) patients had improved their NYHA status at 3 months, 73 (44%) were unchanged and 32 (19%) had deteriorated or died. The differences in symptomatic outcome at three months between the two groups were statistically significant (p = 0.001, chi-square analysis). Both groups demonstrated similar significant improvements in left ventricular dimensions and systolic function.
  
  
  CONCLUSIONS
  Patients with chronic NYHA class IV heart failure are more likely to develop adverse events during initiation and dose titration when compared with less symptomatic patients but are more likely to show symptomatic improvement in the long term. We conclude that carvedilol is a useful adjunctive therapy for patients with NYHA class IV heart failure; however, they require close observation during initiation and titration of the drug.
authors: Heart and Lung Transplant Unit, St. Vincent's Hospital, Sydney, Australia. pmacdonald@stvincents.com.au
authors: P S
authors: PS
authors: Macdonald
authors: A M
authors: AM
authors: Keogh
authors: C L
authors: CL
authors: Aboyoun
authors: M
authors: M
authors: Lund
authors: R
authors: R
authors: Amor
authors: D J
authors: DJ
authors: McCaffrey
mesh_terms: D000206:Actuarial Analysis; D000319:Adrenergic beta-Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems; D000368:Aged; D001315:Australia; D002227:Carbazoles / Q000009:adverse effects / Q000627:therapeutic use*; D000077261:Carvedilol; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005080:Exercise Test / Q000187:drug effects; D005260:Female; D006333:Heart Failure / Q000145:classification / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D011412:Propanolamines / Q000009:adverse effects / Q000627:therapeutic use*; D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol