CORRESPONDENCE: LETTERS TO THE EDITOR
Impact of Carvedilol Before Angiotensin-Converting Enzyme Inhibitor Therapy on Cardiac Function
Yuk Law, MD*
* Oregon Health and Science University, Pediatrics, 707 SW Gaines Road, CDRC-P, Pediatric Cardiology, Portland, OR 97239 (Email: lawy{at}ohsu.edu).
The study by Sliwa et al. (1) is indeed an eye-opener for those who depend on expert opinions such as those from the American College of Cardiology/American Heart Association guidelines (1,2). However, despite a well-executed study, I am not sure the conclusions drawn by the editor and investigators are entirely on the mark. My main criticism is that this is a "how-to" treat and not a "what to" treat study, and as a result it cannot ignore practicality issues. In clinical practice, how often do we see 78 consecutive newly diagnosed patients with New York Heart Association (NYHA) functional classification II to IV go directly to oral anticongestive therapy without the need for parenteral vasodilator intervention initially? In these patients, is it really practical to switch directly from parenteral therapy to oral beta-blockade without the support of an afterload reducing agent? Even among specialists, a measurable dropout rate would be expected if every patient went straight to a beta-blocker. In fact, the concept of using an inodilator to facilitate the commencement of a beta-blocker in those patients who would otherwise not tolerate adrenaline withdrawal or inhibition is for this very reason.
Conversely, concerning the control arm, are there many practitioners who would wait six months before introducing a beta-blocker? Therefore, I am surprised the researchers did not elaborate on the treatment status of the subjects before they were randomized to the carvedilol arm, and whether they encountered difficulties during up-titration. Furthermore, as a significant number of subjects expired during the study (11 of 78, 14% after 12 months), how many required readmission for decompensation and what happened to their beta-blocker dosing regimen?
As for the results, improved biochemical profile, NYHA functional class, and echocardiographic function in the carvedilol-initiated group would indicate that carvedilol is a more "potent" reverse remodeling drug because the final dose of carvedilol was 25% higher in this treatment arm. This would be expected from previous large-scale beta-blocker trials. Any additional agent on top of what is already working may yield a smaller incremental effect as the investigators also demonstrated in the perindopril-initiated arm.
What this "humble" study confirms are that beta-blockers are important in patients with NYHA functional class II or above, that diligence and patience must be used to up-titrate to the highest dose tolerated, and that we should not withhold use of beta-blockade even if a patient feels better without it. The impact of the study is not which agent to initiate first, but that both must be used without delay.
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References
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- Sliwa K, Norton GR, Kone N, et al. Impact of initiating carvedilol before angiotensin-converting enzyme inhibitor therapy on cardiac function in newly diagnosed heart failure J Am Coll Cardiol 2004;44:1825-1830.[Abstract/Free Full Text]
- Leier CV. Dismantling mandates in the treatment of heart failure J Am Coll Cardiol 2004;44:1831-1883.[Free Full Text]
Related Article
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- Karen Sliwa and Mohammed Rafique Essop
J. Am. Coll. Cardiol. 2005 46: 183.
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