• Comparison of lab blood markers of LV remodelling over 6 months, comparing treatment group to placebo group
• Comparison of neurohormonal levels over 6 months, comparing treatment group to placebo group
• Comparison of cardiac electrical stability (heart rate variability, QT dispersion) over 6 months, comparing treatment group to placebo group
• Analysis of DNA at baseline between and within the eplerenone group and the control group – to see if mutations in the gene that encodes aldosterone synthase - CYP112B - predict remodelling and response to aldosterone blockade

• Comparison of lab blood markers of LV remodelling over 6 months, comparing treatment group to placebo group
• Comparison of neurohormonal levels over 6 months, comparing treatment group to placebo group
• Comparison of cardiac electrical stability (heart rate variability, QT dispersion) over 6 months, comparing treatment group to placebo group.
• Analysis of DNA at baseline between and within the eplerenone group and the control group – to see if mutations in the gene that encodes aldosterone synthase - CYP112B - predict remodelling and response to aldosterone blockade

The purpose of this study is to ascertain whether treatment with the drug eplerenone, taken early after a heart attack, prevents or reduces some of the adverse changes that may otherwise naturally occur within the heart muscle, that lead ultimately to weakening of the heart muscle and premature death.

Despite advances in detection and treatment of coronary artery disease, and numerous campaigns to promote healthier lifestyles, ischaemic heart disease (IHD) remains very common worldwide but particularly in the West of Scotland. Following a heart attack, the main pumping chamber - the left ventricle (LV) - will be significantly damaged in around 40% of patients to the extent that it fails to pump as effectively as before. Despite current medical treatment, this failing LV slowly but continuously deteriorates with time (this is known as LV remodelling), which can lead to "heart failure".

Eplerenone, a hormone blocker (aldosterone antagonist), has been shown to reduce death rates and improve symptoms in patients with acute heart attacks - or myocardial infarctions (MI)- who additionally have impaired LV function and heart failure (or diabetes). The researchers assume that eplerenone may exert some of these beneficial effects by preventing or reducing this LV remodelling process.

Cardiac MRI provides very accurate assessment of LV function, such that small numbers of patients only are required to detect differences in LV function over time when comparing one group against another. The researchers are therefore comparing sequential cardiac MRI appearances and measurements in patients with acute MI and LV impairment at baseline (within 2 weeks of the acute MI), 3 months and 6 months. After the first MRI scan, patients are assigned to eplerenone or placebo in addition to usual secondary preventive therapy (double-blinded), which continues for 6 months, after which each patient's involvement in the trial is finished.

As eplerenone has been shown to benefit those with acute MI plus LV impairment and heart failure (or diabetes), such patients cannot ethically be put into a trial in which they may potentially be placed in a placebo group. For this reason, a slightly different cohort of patients are being used - acute MI with LV impairment but without clinical heart failure or diabetes.

• Pitt B, Remme W, Zannad F, Neaton J, Martinez F, Roniker B, Bittman R, Hurley S, Kleiman J, Gatlin M; Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study Investigators. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. 2003 Apr 3;348(14):1309-21. Epub 2003 Mar 31. Erratum in: N Engl J Med. 2003 May 29;348(22):2271.
• Weir RA, Mark PB, Petrie CJ, Clements S, Steedman T, Ford I, Ng LL, Squire IB, Wagner GS, McMurray JJ, Dargie HJ. Left ventricular remodeling after acute myocardial infarction: does eplerenone have an effect? Am Heart J. 2009 Jun;157(6):1088-96.
• Iraqi W, Rossignol P, Angioi M, Fay R, Nuée J, Ketelslegers JM, Vincent J, Pitt B, Zannad F. Extracellular cardiac matrix biomarkers in patients with acute myocardial infarction complicated by left ventricular dysfunction and heart failure: insights from the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) study. Circulation. 2009 May 12;119(18):2471-9. Epub 2009 Apr 27.
• Weir RA, Chong KS, Dalzell JR, Petrie CJ, Murphy CA, Steedman T, Mark PB, McDonagh TA, Dargie HJ, McMurray JJ. Plasma apelin concentration is depressed following acute myocardial infarction in man. Eur J Heart Fail. 2009 Jun;11(6):551-8. Epub 2009 Apr 6.
• Weir RA, Martin TN, Petrie CJ, Murphy A, Clements S, Steedman T, Wagner GS, McMurray JJ, Dargie HJ. Cardiac and extracardiac abnormalities detected by cardiac magnetic resonance in a post-myocardial infarction cohort. Cardiology. 2009;113(1):1-8. Epub 2008 Oct 10.

Inclusion Criteria:

1. Age 18 or above
2. Acute myocardial infarction within last 1-14 days (defined by typical electrocardiogram [ECG] changes and/or elevated cardiac enzymes to at least twice the upper limit of normal)
3. Left ventricular systolic dysfunction (LVSD) based on echocardiographic wall motion score index (WMSI) and left ventricular ejection fraction (LVEF) < 40%
4. Ability to give written informed consent

Exclusion Criteria:

1. Clinical or radiological heart failure
2. Established diabetes mellitus
3. Current use of potassium (K)-sparing diuretics, clarithromycin, nefazodone, itraconazole, ketoconazole, ritonavir, nelfinavir, tacrolimus, cyclosporin.
4. Serum creatinine > 220 µmol/l
5. Serum potassium > 5.0 mmol/l
6. Pregnancy
7. Addison’s disease
8. MRI-incompatible (ferrous) sulphate prosthesis
9. Claustrophobia (unable to tolerate MR environment)
10. Concurrent use of phenytoin, carbamazepine, rifampicin or St. John’s Wort (reduce efficacy of eplerenone).