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 with aspirin

Not for all with stable coronary disease or multiple risk factors

Higher risk subgroups may benefit

The CHARISMA trial (N Engl J Med 2006;354:1706-17) was a large study that enrolled those with known atherosclerotic disease or those with multiple atherosclerotic risk factors. It compared the use of low dose aspirin with or without clopidogrel.

There was no statistically significant reduction of the primary endpoint after a median follow-up of 28 months. The primary endpoint event rate in those with multiple risk factors was essentially the same as in those with known atherosclerotid disease.

A subgroup analysis subsequently reported significant benefit in the group with prior myocardial infarction or stroke of symptomatic peripheral vascular disease (J Am Coll Cardiol 2007; 49: 1982-1988). In this subgroup, only 66 patients needed to be treated to prevent one primary event (death, myocardial infarction, stroke)- the event rate in the aspirin alone group was 8.8% and the rate in the dual therapy group was 7.3%

The ACTIVE-A trial of patients with atrial fibrillation compared low dose aspirin vs aspirin with clopidogrel in patients not eligible for anticoaguation with warfarin- the primary endpoint of the trial was to assess for reduction of stroke. However, interestingly, the trial also found a reduction in risk of myocardial infarction in these patients when treated with dual therapy compared to aspirin alone.

Conclusions:

• The overall findings of the CHARISMA did not find evidence for benefit of dual antiplatelet therapy in those with stable atherolsclerotic disease or in those with multiple risk factors.
• Hypothesis generating sub-groups analysis of the CHARISMA trial suggests that those with manifest atherosclerotic disease may benefit from dual antiplatelet therapy.