Letter Regarding Article by Weintraub et al, “Cost-Effectiveness of Eplerenone Compared With Placebo in Patients With Myocardial Infarction Complicated by Left Ventricular Dysfunction and Heart Failure”
To the Editor:
An economic analysis of a treatment contributes greatly to decisions about its use in individuals and large populations. However, the analysis performed on the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival (EPHESUS) trial1 would be more relevant if eplerenone had been compared with spironolactone rather than to placebo. We agree with the the statement of Weintraub et al that “there is no direct comparison of eplerenone to spironolactone, making a comparison of the two aldosterone blockers speculative.” Still, even at the time of the beginning of this trial, spironolactone had been demonstrated to be an inexpensive, clinically effective aldosterone antagonist in the setting of heart failure. The EPHESUS investigators previously argued that because spironolactone has an unknown effect in the setting of acute myocardial infarction, there was no ethical imperative to have used an active control–equivalence design.2 Although that is true, there was and is a distinct public health imperative for such a design. It is critically important to know rather than speculate about whether 2 medications with similar effects but quite disparate costs and side-effect profiles have equivalent mortality and morbidity outcomes. Unfortunately, there is no requirement or incentive for manufacturers to make such comparisons, and public research funds are not sufficient to systematically clarify such uncertainties. In this case, the lack of a spironolactone arm in EPHESUS has left clinicians with the ethical ambiguity—if not dilemma—about whether they are needlessly wasting healthcare resources by using eplerenone rather than spironolactone in EPHESUS-type patients.
Weintraub WS, Zhang Z, Mahoney EM, Kolm P, Spertus JA, Caro J, Ishak J, Goldberg R, Tooley J, Willke R, Pitt B. Cost-effectiveness of eplerenone compared with placebo in patients with myocardial infarction complicated by left ventricular dysfunction and heart failure. Circulation. 2005; 111: 1106–1113.