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

Clopidogrel for Secondary Prevention
Only slightly better than Aspirin

The CAPRIE trial compared the use of low dose aspirin with clopidogrel in a large number of patients with symptomatic peripheral vascular disease or those with recent stroke or recent myocardial infarction. Over 19,000 patients were randomised, with a mean follow-up of almost two years.

The primary endpoint of the trial was ischaemic stroke, myocardial infarction and vascular death. Intention to treat analysis revealed patients treated with clopidogrel had an annual event rate of 5.32% compared with 5.83% with aspirin. This small difference was statistically significant in this large trail.

Adverse side-effects including risk of gastrointestinal bleeding and neutropenia were similar in the two groups.

Further analysis of this study were reported in the prestigous journal Circulation in 2001. I have not reviewed this paper but the abstract reports that patients with previous CABG surgery obtain substantially greater benefits from use of clopidogrel- the relative risk reduction of major events (including rehospitalisation) was over 30%. The inclusion criteria of the CAPRI trial are noteworthy- it is possible that "stable" patients may obtain less additional benefit over low dose aspirin, compared with patients that have had a recent acute event.

The CURE trial showed that use of clopidogrel with aspirin provided greater benefits compared to use of aspirin alone after acute coronary syndromes.

In conjunction with other evidence that has accumulated in favour of clopidogrel most cardiologists believe that there is little doubt about the effectiveness of this drug as monotherapy in patients who can not take low dose aspirin. The CURE trial evidence also suggests that there are significant benefits from the combined use of low dose aspirin and clopidogrel after acute coronary syndromes.

• A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee. Lancet 1996;348:1329-1339
• Superiority of clopidogrel versus aspirin in patients with prior cardiac surgery, Circulation 2001;103:363-368