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Letter to the Editor
Editor, – I read with interest the new drug review of eplerenone (Aust Prescr 2005;28:130-1). This review contains a number of statements that require clarification.
First, it is stated that gynaecomastia and breast pain still occur with eplerenone (as has been a major adverse effect of spironolactone). This is a somewhat disingenuous interpretation of the data as in fact no study has shown an excess of these events with eplerenone compared to placebo. As with any adverse effect, there is a spontaneous background event rate that is not further added to by eplerenone therapy.
Next, it is implied that because spironolactone reduces relative risk of death by 30% in patients with severe heart failure it is a more effective drug than eplerenone, that 'only' reduced risk of death by 15% in post-myocardial infarction (MI) heart failure patients. Again, making comparisons regarding the impact of therapies across trials is poor science and tells us nothing about the relative merits of individual drugs because of the differing disease states and background treatments in the differing trials.
Finally, and most importantly, it is stated that spironolactone is well known and inexpensive and 'thus unlikely to be superseded until more data about eplerenone are available'. This statement clearly implies that the two drugs can be used interchangeably for the same clinical indication. Just as eplerenone should not be given to patients with severe heart failure (because it has not as yet been tested in such a patient population) the same is true of spironolactone in post-MI heart failure. The suggestion that these drugs are interchangeable challenges fundamental principles of evidence-based prescribing and should be utterly rejected.
Professor and Director
NHMRC Centre of Clinical Research Excellence in Therapeutics
Professor Krum has been a consultant to Pfizer, manufacturer of eplerenone.
Gynaecomastia may take several months to develop. While the frequency has not increased during studies of heart failure, it has been higher than with placebo in studies of hypertension. According to data reviewed by the US Food and Drug Administration 1% of men taking eplerenone for hypertension developed breast symptoms.1
While the selectivity of eplerenone may explain why it has less effect on sex hormones than spironolactone, it is not clear if this results in greater efficacy. If the efficacy depends on aldosterone antagonism then spironolactone should also be effective. Spironolactone is known to be effective in heart failure, but, as Professor Krum highlights, the supporting evidence does not come specifically from patients who start treatment 3-14 days after an acute myocardial infarction. This has resulted in the cost-effectiveness of eplerenone being compared to placebo rather than spironolactone.2
As 50 patients need to be treated with eplerenone for a year to prevent one death, there is a need to find out if spironolactone could be more cost-effective. We would encourage a comparative trial of eplerenone and spironolactone, although there may be no incentive for the manufacturers to carry out this comparison.
- US Food and Drug Administration. Clinical review: eplerenone. http://www.fda.gov/cder/foi/nda/2002/21-437_Inspra_Medr_P5.pdf[cited 2006 Mar 8]
- Pharmaceutical Benefits Advisory Committee. Public summary document: eplerenone. http://www.health.gov.au/internet/wcms/publishing.nsf/Content/pbac-psd-eplerenone [cited 2006 Mar 8]