Myocardial Infarction
Optimising Drug Therapy

• Check List for Drug Therapy

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• Clopidogrel
• Clopidogrel alone only slightly better than aspirin alone
• Clopidogrel with aspirin better than aspirin alone after an acute coronary event
• Clopidogel with aspirin probably is better than aspirin alone in stable coronary disease

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• Warfarin
• Warfarin- instead of (or as well as) aspirin for secondary prevention

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• Beta-blockers
• After MI
• After large MI
• In heart failure

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• ACE-inhibitors
• After MI
• After large MI
• Use maximal dosages in heart failure
• For most patients after MI

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• Aldosterone antagonists
• Spirinolactone in heart failure

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• Lipid modifying therapy after MI

Spirinolactone in those with heart failure

The RALES study enrolled a total of 1663 patients with heart failure. Patients with serum creatinine levels less than 0.21mmol/l were enrolled. There was high use of ace-inhibitor therapy but beta-blocker use was low.

Patients were randomised to placebo or spirinolactone- patients were prescribed 25mg/d but the dose could be increased to 50mg/d if there was worsening heart failure or some other evidence of progression.

The study showed a much lower mortality in patients treated with spirinolactone, 35% vs 46%, a 30% reduction in mortality in this very high risk group of patients (with an average ejection fraction of 25%). Given this large benefit, spirinolactone was rapidly accepted for routine use by many cardiologists on the basis of the results of this single trial.

Subsequently, the EPHESUS study was published, in this study a selective aldosterone blocker was used. This study enrolled patients with heart failure after myocardial infarction. After a mean follow-up of 16 months, it confirmed a significant mortality reduction from aldosterone blockade (15% reduction of relative risk, absolute risk reduced from 16.7% to 14.4%), including a 21% reduction in sudden death from cardiovascular causes. About 40% of deaths from cardiovascular causes were classifed as being "sudden".

The mortality rate in the control group was lower than in the control group of the RALES study. In EPHESUS, the mortality reduction was not as great as in the RALES study- possibly because the participants had a higher ejection fraction and there was greater use of beta-blockers compared to the RALES study.

As is often seen after acute events, in the EPHESUS study there was an initial period of increased risk of cardiovascular death which then decreased to lower levels.

References:

• The effect of Spirinolactone on morbidity and mortality in patients with severe heart failure. N Eng J Med 1999;341:709-17
• Eplerenone, a Selective Aldosterone Blocker, in Patients with Left Ventricular Dysfunction after Myocardial Infarction. N Eng J Med 2003;348:1309-1321