The effect of spironolactone on morbidity and mortality in patients with severe heart failure
This study of spironolactone in patients with severe congestive heart failure revealed a significant reduction (by about 30% relative risk) in death and hospitalizations among treated patients. These patients were receiving reasonable therapy with diuretics, ACE inhibitors and digitalis, and, although only 10% were on beta-blockers, the benefit was, if anything, greater in this subgroup. The results of the study should be applicable to a fairly large segment of patients with severe CHF, since the exclusion criteria should not rule out the majority of patients in clinical practice.
The authors do not state whether or not baseline aldosterone levels were obtained in these patients. If they were, it would be interesting to see whether the benefit of spironolactone was concentrated in patients with higher aldosterone levels. If so, the drug could be targetted to those who would benefit the most.
I was initially surprised to see a major pharmaceutical company like Searle sponsoring a trial of such an old drug, but Searle is also developing a newer aldosterone receptor blocker, eplerenone, which may cause less gynecomastia. Whether or not this newer drug will be as effective in CHF remains to be seen.
September 7, 1999
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September 12, 1999
We read with interest the publication of the results of the RALES study as this adds to the knowledge on the pharmacological treatment of severe heartfailure (1). Earlier this year two trials on treatment with selective beta-blockers were published (2,3). Bisoprolol (CIBIS- II study) and metoprolol (MERIT-HF trial) respectively showed a significant effect on mortality compared to placebo when added to conventional treatment. The impact of the results of these trials is considerable and will basically change our treatment of (systolic) heart failure.
We want to make two points. Firstly, none of these trials has been properly reported according to the CONSORT guidelines for reports of randomised controlled trials (4). How many patients were initially involved and from where did they come? The omission of information on eligible patients is hard to understand, as the external validity depends on the representativity of included patients. Secondly, it would be clarifying if all major trials also reported the NNTs (with 95 % confidence intervals).
Hans Liedholm, MD PhD, Agneta Björck Linné, B Pharm
1. Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, Palensky J, Wittes J, for the Randomized Aldactone Evaluation Study Investigators. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N Engl J Med 1999;341: 709-17.
2. CIBIS-II Investigators. The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial. Lancet 1999;353:9-13.
3. MERIT-HF Study Group. Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL randomised intervention trial in congestive heart failure (MERIT-HF). Lancet 1999;353:2001-7.
Date: September 22, 1999
In the latest issue of Circulation (Circ 1999;100:1311) the SOLVD investigators published a restrospective analysis addressing the relationship between use of diuretics and arrhythmic deaths. The relative risks of deaths according to the class of diuretic used is shown below. The influence of non-potassium sparing diuretics was independent of group assignment, i.e., enalapril or placebo.
Therefore, it is possible that part of the mortality reduction observed in the RALES study could be attributed to the potassium-sparing action of spironolactone.
I also have some doubts whether we might extrapolate the RALES results to a larger population under beta-blocker use, since only 10% were effectively taking such drugs. Nowadays, the use of beta-blockers in heart failure is consistently increasing and it remains to be proved whether spironolactone adds incremental benefit beyond that of a combination of ACEI and beta-blocker to standard digitalis and diuretic therapy.
Sergio Kaiser, MD
Date: November 11, 1999
In RALES the number of patients in atrial fibrillation is not stated. Even
January 24, 2000From: Javier Ena (firstname.lastname@example.org)
Received: November 30, 1999
I read with great interest your article and I was surprised by the large proportion of patients that dropped out from study (24% in the placebo group and 26% in the spironolactone group). Could you detail in numbers the reasons for the drop-outs. In addition, there is some less degree of cardiac failure in patients taking spironolactone (27% in class IV in the spironolactone group; 31% in class IV in the placebo group). Were the differences in mortality and hospitalization maintained after controlling for NYHA class?. Thanks for your answer.
J. Ena MD (Alicante. Spain)
January 24, 2000
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