Reply : Mineralocorticoid Receptor Antagonism in Acute Myocardial Infarction : Who Benefits ?

The letter by Drs. Weir and Petrie points to the hypothetic benefit of mineralocorticoid receptor blockade (MRA) in preventing left ventricular remodeling and reducing mortality in patients with myocardial infarction (MI) but preserved left ventricular function. Although the ALBATROSS (Aldosterone Lethal Effects Blockade in Acute Myocardial Infarction Treated With or Without Reperfusion to Improve Outcome and Survival at Six Months Follow-up) study failed to demonstrate a benefit of MRA in the global MI population, it reported a possible reduction of mortality only in the ST-segment elevation MI subgroup (1,229 of 1,603 patients). The potential mechanisms of such an effect on mortality in ST-segment elevation MI may be a prevention of the arterial occlusion-related adverse remodeling and/or potentially lethal arrhythmia, as suggested by the authors.

The effect of MRA on adverse remodeling has been supported by preclinical and limited clinical data showing aldosterone’s deleterious effects both on vascular and myocardial levels and the attenuation of remodeling and collagen turnover by MRAs. Such effects may, however, take a long time to be revealed, especially among patients at low risk of remodeling, as recruited in the REMINDER (A Double-Blind, Randomized, Placebo-Controlled Trial Evaluating the Safety and Efficacy of Early Treatment With Eplerenone in Patients With Acute Myocardial Infarction) study and ALBATROSS trials. Hence, a longer follow-up of these patients may be of interest and is being considered for ALBATROSS.

The absence of an MRA effect on rates of ventricular arrhythmia in the EPHESUS (Eplerenone Post-AMI Heart Failure Efficacy and Survival Study), REMINDER, and ALBATROSS studies may not be interpreted as proof of the absence of any effect on lethal arrhythmia. Considering the controversial prognostic impact of arrhythmia occurring early after MI and the absence of an MRA effect on arrhythmia detected during the in-hospital period, we cannot exclude, however, a later effect supported by the trend toward a decrease in rates of sudden cardiac death in EPHESUS and ALBATROSS.

Remodeling is a substrate of arrhythmia and its prevention leads to a reduction of both left ventricular dysfunction and life-threatening arrhythmia. Hence, the issue of serial assessment of remodeling is of great importance. Unfortunately, ALBATROSS was an academic research project with limited financial support, and the initially considered imaging substudy could not be funded.

To answer the other 2 questions raised by the authors concerning the STEMI patients included in ALBATROSS, a specific and detailed analysis of this subgroup is being held and will be shortly submitted for publication.