CORRESPONDENCE: LETTERS TO THE EDITOR
Reply
Karen Sliwa, MD, PhD, FESC* and
Mohammed Rafique Essop, MD, FACC, FRCP
* Cardiology and Medicine, Baragwanath Hospital, University of Witwatersrand, P.O. Bertsham, Johannesburg 2013, South Africa (Email: hahnle{at}netactive.co.za).
We appreciate the interest in our recently published study (1). Dr. Law raises several concerns, some of which we find puzzling. Baragwanath is the only hospital serving a population of some three million; with a bed capacity of 3,300, it is the largest hospital in the Southern Hemisphere and has a cardiac clinic that sees some 25,000 patients annually. In this context, it is not difficult to understand how 100 or more new patients with idiopathic dilated cardiomyopathy might be recruited each year. The majority of these patients receive workup and therapy as outpatients. For us, and surely for many other busy units, these patients represent "real clinical practice." Dr. Law questions the six-month delay in starting carvedilol in the "ACE-I first" group. We cannot understand his concern as this in essence was the design of the study to answer the issue at hand. Our study and the CIBIS-III trial have chosen monotherapy with an ACE inhibitor versus a beta-blocker for six months followed by combination of both agents to study the impact of the individual and subsequent combination effect of each drug on left ventricular (LV) function. There is no direct scientific evidence of the exact duration when an impact on remodeling of the left ventricle can be expected. However, it will be several months rather than a few weeks.
The question as to the mechanism of benefit is speculative but does not detract from the important finding that the beta-blocker-first strategy was superior. The notion that beta-blockade may be harmful when initiated in patients with advanced heart failure was clearly dispelled by the results of the COPERNICUS study (2), which showed carvedilol to be beneficial even in class IV heart failure.
We fully agree with the sentiments of Dr. MacFadyen et al. regarding the pharmacologic importance of the sequence in which drug therapy is initiated, especially in a condition such as heart failure, where multidrug therapy is the rule and where optimal doses may be severely handicapped by hypotension. Both ethnicity and the response to drug therapy are important issues, and it is notable that the majority of our patients were black Africans who have been shown to respond differently to ACE inhibitors in the setting of hypertension and possibly also in heart failure (3). That is why we believe it is important that further investigation in larger studies, using different ethnic groups and other etiologies of heart failure, such as ischemic cardiomyopathy, be undertaken, first, to confirm our results and, second, to determine their generalizability. The efforts of the CIBIS-III investigators (4) and their comments on our findings are appreciated and we eagerly await publication of their results.
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References
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- Sliwa K, Norton GR, Kone N, et al. Impact of initiating carvedilol before angiotension-converting enzyme inhibitor therapy on cardiac function in newly diagnosed heart failure J Am Coll Cardiol 2004;44:1825-1830.[Abstract/Free Full Text]
- Packer M, Coats A, Fowler M, et al. Effect of carvedilol on survival in severe chronic heart failure. COPERNICUS N Engl J Med 2001;344:1651-1658.[Abstract/Free Full Text]
- Exner DV, Dries DL, Domanski MJ, Cohn JN. Lesser response to angiotensin-converting enzyme inhibitor therapy in black compared with white patients with left ventricular dysfunction N Engl J Med 2001;344:1351-1357.[Abstract/Free Full Text]
- Willenheimer R, Erdmann E, Follath F, et al. CIBIS-III investigators Comparison of treatment initiation with bisoprolol versus enalapril in chronic heart failure patientsrationale and design of CIBIS-III. Eur J Heart Fail 2004;6:493-500.[CrossRef][ISI][Medline]
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