CORRESPONDENCE: LETTER TO THE EDITOR
Reply
Clyde W. Yancy, MD, FACC, FAHA, FACP*
* UT Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9047 (Email: clyde.yancy{at}utsouthwestern.edu).
The letter from Dr. Aguiar-Souto and colleagues has been reviewed and their comments are very much appreciated. The American College of Cardiology/American Heart Association (ACC/AHA) 2005 guidelines for chronic heart failure ascribed a class IIa, level of evidence A, recommendation to the adjunctive use of isosorbide dinitrate/hydralazine to standard therapy in patients with persistent symptoms of heart failure without a race designation. The section of the guidelines addressing special populations likewise ascribed a class IIa, level of evidence A, recommendation to the use of combined vasodilator therapy in addition to standard therapy in blacks with functional class III or IV heart failure (1).
The rationale for this classification is based on the preponderance of data demonstrating the benefit of combined vasodilator therapy in symptomatic heart failure. The Vasodilator Heart Failure Trials (V-HeFT I and V-HeFT II) demonstrated a mild survival advantage for this regimen in V-HeFT I and improvement in the important surrogate end points of exercise capacity and left ventricular function in V-HeFT II. A subsequent retrospective analysis of both trials demonstrated that the majority of the benefit was seen in black patients, but the effect was not absent in the non-black cohort (2). The significant results now demonstrated in the African American Heart Failure Trial (A-HeFT) confirm the advantage of this regimen (3). A strongly held opinion of the guideline writing committee is that there are insufficient data to assert that race alone is the operative variable that determines responsiveness to this regimen. Thus, two clinical trials, V-HeFT I and A-HeFT, demonstrate benefit in patients with symptomatic heart failure, and a third trial, V-HeFT II, is consistent with a favorable effect of vasodilator therapy in symptomatic heart failure.
A class IIa recommendation states that a given treatment or intervention "is reasonable" and that the risk-benefit ratio is decidedly favorable. Level A evidence for a class IIa recommendation requires multiple positive data sources, but also allows for a recommendation in favor of therapy despite incongruent data from smaller datasets and retrospective analyses. Given multiple trials demonstrating the benefit of combined vasodilator therapy in diverse populations, the class recommendation appears reasonable for both the general population and for blacks with symptomatic heart failure, and the level of evidence is indeed consistent with the several confirmatory trials.
The class IIb recommendation for the addition of an angiotensin receptor antagonist to already effective therapy is reasonable based primarily on a morbidity-only advantage seen in the CHARM-Added trial (4). The data regarding the use of nebivolol had not been published during the deliberations of the guideline writing committee; thus, they were not available to be incorporated into the 2005 statement.
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References
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- Hunt SA, Abraham WT, Chin MH, et al. ACC/AHA 2005 guideline update for the diagnosis and management of chronic heart failure in the adult. Available at: http://www.acc.org/clinical/guidelines/failure/index.pdf. Accessed February 2006..
- Carson P, Ziesche S, Johnson G, Cohn JN, Vasodilator-Heart Failure Trial Study Group Racial differences in response to therapy for heart failureanalysis of the vasodilator-heart failure trials. J Card Fail 1999;5:178-187.[CrossRef][Medline]
- Taylor AL, Ziesche S, Yancy C, et al. African-American Heart Failure Trial investigators Combination of isosorbide dinitrate and hydralazine in blacks with heart failure N Engl J Med 2004;351:2049-2057.[Abstract/Free Full Text]
- McMurray JJ, Östergren J, Swedberg K, et al. CHARM investigators and committees Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function taking angiotensin-converting-enzyme inhibitorsthe CHARM-Added trial. Lancet 2003;362:767-771.[CrossRef][ISI][Medline]
Related articles in JACC:
- Diagnosis and Management of Chronic Heart Failure
- Pablo Aguiar-Souto, Pablo Garcia-Pavia, Lorenzo Silva-Melchor, and Francisco J. Ortigosa
JACC 2006 48: 223.
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