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

Lipid Modifying Therapy for Secondary Prevention

Numerous randomised clinical trials have now proved the value of lipid-modifying therapy for secondary prevention.

• Even patients with “normal” cholesterol levels obtain significant benefit from statin therapy. If simvastatin is used then most patients should be treated with at least 40mg daily of this drug
• The large statin trials showed reduction in fatal cardiovascular events, in myocardial infarction, in new onset angina and need for revascularisation
• Trials now show that patients continue to get additional benefit with lowering of total cholesterol levels below previous target levels.
• The United States of America’s guidelines (ATP III guidelines) suggest lowering LDL-cholesterol below 2.5mmol/ (LDL cholesterol should only be calculated from fasting lipid profiles). However, the latest update (July, 2004) suggests an even lower target for secondary prevention. This update also suggested that lowering LDL cholesterol below 2.5mmol/l was an option for primary prevention in those at moderately increased risk. Whether publication of the TNT trial in March, 2005 will lead to a change in target LDL cholesterol for all patients remains to be seen.
• The NZ Guidelines recommend lowering LDL cholesterol below 2.5mmol/l for secondary prevention but the target for those with venous coronary bypass grafts is LDL less than 2.0mmol/l.
• There will be debate about cost-effectiveness of more intensive therapy, but it seems reasonable, at the least, to lower LDL cholesterol levels below 1.8 mmol/l in high risk groups which might include:
  • those more likely to have or known to have more advanced and diffuse coronary disease,
  • diabetics, and
  • some ethnic groups (such as South Asians) that are known to develop heart disease decades earlier than Caucasians.
  • Prospective trial data are awaited but consideration should also be given to more intensive LDL cholesterol lowering in those with high CRP levels despite statin therapy and lifestyle measures.
• The initial goal (except in those with severe triglyceridaemia) should be to lower the LDL cholesterol level. Once this goal has been reached, attention can then be focused on non-HDL cholesterol (ATP III guidelines). Statins and other agents also raise HDL cholesterol levels and lower triglyceride levels. Resins do not affect triglyceride levels. It is not certain how much benefit is obtained by raising HDL cholesterol levels when LDL cholesterol levels are lowered intensively.
• Fibrates such as gemfibrozil seem to have the same benefits as statins such as simvastatin, when used in patients with the typical “metabolic syndrome” lipid profile- of average total cholesterol levels, raised triglyceride levels and low HDL cholesterol levels. However, it seems likely that high dose atorvastatin (80 mg daily) will be superior to fibrate therapy alone.

The following agents can be used:

• Statins
High dose atorvastatin has been shown in the TNT and PROVE-IT studies to be effective and safe. The A to Z trial raised concerns about increased risk of rhambdomyolysis with doses of simvastatin greater than 40mg daily.

In some studies high dose atorvastatin has lowered HDL cholesterol or raised HDLC levels on slightly, thus in patients with low HDL cholesterol we may wish to consider using simvastatin with ezetimibe; provided we remember that to date outcome data from large randomised trials are only available for high dose atorvastatin.
• Fibrates
Fibrates are well tolerated and give the same benefits as statins in those with dyslipidaemia typical of the "metabolic syndrome". These agents are also used in combination with statins if there is persistent hypertriglyceridaemia or low HDLC levels. Gemfibrozil increases the risk of statin myopathy, fenofibrate may not have the same risk because it does not interfere with statin catabolism.
• Resins
These agents are not used often because of poor tolerability and interference with absorption of other drugs.
• Nicotinic acid
Can be used to raise HDLC and lower LDLC levels. There is a need to use low doses and progressively increase the dose to avoid problems with hot flushes. Aspirin can be taken prior to a dose of nicotinic acid to prevent hot flushes. The drug can also cause liver enzymes abnormalities, and raise glucose and uric acid levels.
• Cholesterol absorption inhibitors, such as ezetimibe
These agents have been shown to lower LDLC levels further when used in combination with statins.

Hitesh Patel, Cardiologist
28th March, 2005
Modified 12th June, 2005