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J Am Coll Cardiol, 1999; 33:924-931
© 1999 by the American College of Cardiology Foundation
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CLINICAL STUDIES

Tolerability and efficacy of carvedilol in patients with New York Heart Association class IV heart failure

Peter S. Macdonald, MBBS, PhD, FRACPa, Anne M. Keogh, MBBS, MD, FRACPa, Christina L. Aboyoun, BAa, Mayanna Lund, MBBS, FRACPa, Raul Amor, MBBS, FRACPa and Dermot J. McCaffrey, MB, MRCPa

a Heart and Lung Transplant Unit, St. Vincent’s Hospital, Sydney, Australia

Manuscript received May 6, 1998; revised manuscript received October 23, 1998, accepted December 15, 1998.

Reprint requests and correspondence: Associate Professor Peter Macdonald, Heart & Lung Transplant Unit, St. Vincent’s Hospital, Darlinghurst, NSW, 2010 Australia
pmacdonald{at}stvincents.com.au

OBJECTIVES

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.

Abbreviations and Acronyms
  ANOVA = analysis of variance
  ANZ = Australia and New Zealand
  LV = left ventricular
  LVEDD = left ventricular end-diastolic dimension
  LVESD = left ventricular end-systolic dimension
  NYHA = New York Heart Association




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