LETTERS TO THE EDITOR
Reply
Peter Macdonald, PhD, FRACPa
a Associate Professor of Medicine, Staff Cardiologist, Heart and Lung Transplant Unit, Victoria Street, Darlinghurst, NSW 2010 Australia
We thank Dr. Hoffman for his comments. As stated in our report (1), the actuarial survival rate for patients in New York Heart Association functional class IV heart failure at one year was 84% and the one-year mortality rate was 16%. Overall, 10 patients in functional class IV died within the first year after commencement of carvedilol. As shown in Figure 1 (page 926), the deaths occurred throughout the year, with no apparent clustering at the time of initiation or titration of carvedilol. Causes of death were judged to be progressive heart failure in five patients and sudden cardiac death in five patients. All five patients who died suddenly were taking carvedilol at the time of their death and had been treated for 6, 74, 96, 127 and 203 days, respectively. Deaths from progressive heart failure occurred at days 41, 46, 142, 153 and 259. Carvedilol was withdrawn before death in all five patients who subsequently died of progressive heart failure. The reason for withdrawal in all five patients was worsening heart failure, and the period between carvedilol withdrawal and death ranged from 23 to 228 days.
We recognize that not all patients in functional class IV heart failure referred to our institution were challenged with carvedilol; however, we believe our patients are comparable to those in class IV included in the other studies that we have cited. For instance, in the CONSENSUS Study (26) in which the 1-year mortality rate for enalapril was  40%, all patients had to be stable on medical therapy for 2 weeks before trial entry. Patients on intravenous inotropic therapy and mechanical support were excluded. Similarly, in the study of Lee and Packer (19), only patients with stable chronic functional class IV heart failure were included. The one-year mortality rate in this study for patients receiving angiotensin-converting enzyme inhibitors was 50%.
As stated in the Discussion of our report, we can only speculate on the impact of carvedilol on survival; however, we believe that a one-year mortality rate of only 16% compares favorably with historic reports such as those cited. The recently published Cardiac Insufficiency Bisoprolol Study (CIBIS-II) (2) provides the strongest evidence to date that the beneficial effects of beta-blockers in heart failure extend to patients who are in functional class IV at baseline. Seventeen percent of 2,647 patients entered into CIBIS-II were in functional class IV at baseline. Active treatment with bisoprolol reduced mortality by 34% as compared with placebo, with no significant difference between class III and class IV. Patients with severe functional class IV heart failure and recent instability were excluded from CIBIS-II, as in our study.
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References
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- Macdonald PS, Keogh AM, Aboyoun CL, Lund M, Amor R, McCaffrey DJ. Tolerability and efficacy of carvedilol in patients with New York Heart Association class IV heart failure. J Am Coll Cardiol. 1999;33:924–931[Abstract/Free Full Text]
- The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial. Lancet. 1999;353:9–13[CrossRef][Medline]
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