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

Ace-inhibitors in those with atherosclerotic disease

HOPE and EUROPA, and now PEACE

Analysis of the early ace-inhibitor trials such as SAVE has suggested that ace-inhibitors reduced the risk of myocardial infarction. The benefits of routine use of ace-inhibitors in patients that do not have significant impairment of LV systolic function has been assessed further.

The HOPE study prospectively assessed this possible benefit. The HOPE study included over 9000 patients older than 55 years who had evidence of vascular disease or had diabetes with at least one other cardiovascular risk factor, and who were not known to have impaired left ventricular function.

Participants were randomly assigned to receive ramipril 10 mg daily or placebo for a mean of 5 years, although the study was stopped a few months earlier because of the benefits of ramipril therapy.

The combined outcome of MI, stroke, or death from cardiovascular causes occurred significantly less often with ramipril than placebo after a mean follow-up of five years (14.0 vs. 17.8%, relative risk 0.78, p less than 0.001).

In other words, about 45 patients would need to be treated for five years to prevent one event, as defined in this study. The benefits probably continue to accumulate and the number to treat will be less over a longer period.

Subsequently, the EUROPA trial concluded. It has enrolled patients with coronary disease. This trial showed that the ace-inhibitor perindopril also reduced cardiovascular death, MI or cardiac arrest after a mean 4.2 years follow up

There continues to be some debate about the mechanism of benefit- some argue that the benefits may be entirely due to the lowering of blood pressure with use of ace-inhibitors rather than any specific properties of these agents.

In November, 2004, the PEACE trial results were presented at the AHA meeting and the study findings published in the New England Journal of Medicine. This study's findings will need to be carefully considered. The study did not find any benefit from the routine use of trandalopril in patients with coronary artery disease who did not have an established indication for use of these agents. The authors compare their findings with the HOPE ane EUROPA trials. The PEACE trial participants were at lower risk with lower event rates than the other trials. One possible implication of these findings is that non-diabetic patients with coronary disease and with good left ventricular systolic funtion and whose modifiable risk factors are well controlled may not obtain much benefit from routine use of ace-inhibitor therapy.

Prior to the publication of the PEACE trial many were advocating the routine use of ace-inhibitors in patients with atherosclerotic disease or those with diabetes with other risk factors. At the least ace-inhibitors should be used in preference to all anti-hypertensive agents other than beta-blockers in this group of patients. The PEACE trial results seem to indicate that there may be a subgroup of patients that may not obtain much benefit from routine use of ace-inhibitor therapy.

Hitesh Patel, Cardiologist
27th November, 2004

• Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med 2000;342:145–53
  
• Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA study). Lancet 2003;362:782–88
• PEACE Trial investigators. Angiotensin-converting-enzyme inhibition in stable coronary artery disease. N Engl J Med; published online before print November 7, 2004.