doi: 10.1161/01.CIR.0000124885.70372.41
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(Circulation. 2004;109:e182.)
© 2004 American Heart Association, Inc.
Correspondence |
Aldosterone Levels After Angiotensin Receptor Blocker Treatment
University and University Hospital Maastricht, P. Debyelaan 25, PO Box 5800, 6202, AZ Maastricht, The Netherlands, RFOL{at}cardio.azm.nl
To the Editor:
Cohn and colleagues1 reported a sustained decrease of plasma aldosterone concentration after treatment with valsartan in the Valsartan Heart Failure trial. After 24 months, aldosterone levels were still decreased by 17.4% compared with baseline. The authors concluded that after 2 years, there was no evidence of aldosterone escape. However, Figure 1 in their article demonstrates a clear and continuous increase in aldosterone levels between 4 and 24 months, which appears statistically significant.
This increase parallels the placebo group, suggesting a similar progression of heart failure. Currently, there are no published data that demonstrate the effects of an aldosterone antagonist on top of an angiotensin receptor blocker in patients with congestive heart failure. If aldosterone levels indeed increase between 4 and 24 months, this suggests that there is some degree of aldosterone escape, which underlines that an aldosterone antagonist might convey additional benefit on top of angiotensin receptor blocker treatment.
References
1. Cohn JN, Anand IS, Latini R, et al. Sustained reduction of aldosterone in response to the angiotensin receptor blocker valsartan in patients with chronic heart failure: results from the valsartan heart failure trial. Circulation. 2003; 108: 1306–1309.
Response
Cardiovascular Division, Department of Medicine, University of Minnesota Medical School, Minneapolis, Minn, cohnx001{at}umn.edu
VA Medical Center, Minneapolis, Minn
Istituto "Mario Negri", Milan, Italy
Novartis Pharmaceuticals Corporation, East Hanover, NJ
One must be cautious in analyzing the apparent sequential changes in hormone levels in the two treatment groups in the Valsartan Heart Failure Trial (Val-HeFT) because the analysis at each time point is compared with the baseline for that patient group, and the number of patients declines over time according to time of follow-up and dropouts. Sequential changes could be explored only in an analysis of "completers"—that is, patients who had measurements at each time point—and that would, of course, exclude patients who died. Such an analysis of the 1334 completers reveals that the suppression of aldosterone levels in the valsartan group compared with the placebo group is constant throughout follow-up, thus confirming that there is no "escape." On the other hand, there is a significant increase in aldosterone levels in both groups from 12 to 24 months. Therefore, a progressive increase over time, previously observed with B-type natriuretic peptide in Val-HeFT and with plasma norepinephrine in Val-HeFT and in previous trials, is consistent with the natural history of progressive heart failure.
As explained in our report,1 the aldosterone data provide no obvious rationale for the use of aldosterone inhibitors in patients treated with valsartan. Nonetheless, the data do not exclude a benefit from blocking the residual circulating or tissue levels of aldosterone, an action through an alternative occupant of the receptor, or a long-term benefit by inhibiting the effect of the progressive increase in aldosterone levels over time.
Footnotes
Dr Cohn has received grant support, honoraria, and consulting fees from Novartis Pharmaceuticals Corp, Inc, or Novartis Pharma AG, the study sponsor. Drs Anand and Latini have received grant support and honoraria from Novartis, and Drs Glazer and Chiang are employees of Novartis.
References
1. Cohn JN, Anand IS, Latini R, et al. Sustained reduction of aldosterone in response to the angiotensin receptor blocker valsartan in patients with chronic heart failure: results from the valsartan heart failure trial. Circulation. 2003; 108: 1306–1309.
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