Viewpoint: Use of cholesterol-lowering agents

Dr Iqbal Malik discusses the use of lipid-lowering agents in preventing cardiovascular disease.

There has been much debate over the use of lipid-lowering agents in preventing morbidity and mortality from cardiovascular disease (CVD).

Although the clinical effectiveness data are published and can be discussed, the absence of good quality cost-effectiveness data means that the focus of the debate started at the wrong point.

Evidence for lipid lowering
In 1994, the landmark 4S study showed mortality reduction was possible in patients who had previously suffered MI and had average UK cholesterol levels (total cholesterol 6.5mmol/l, LDL 5.0mmol/l) by treating with simvastatin 20-40mg.

Since then a number of trials have confirmed this finding in both high risk (secondary prevention) and lower risk (primary prevention) patients.

Treatment level
The next question is then what target to treat down to. The Joint British Societies (JBS2) guidelines suggest that there is clinical evidence of benefit to reducing lipids below total cholesterol <4mmol/l, and LDL cholesterol <2mmol/l. DoH guidelines, however, have re-iterated that total cholesterol <5mmol/l and LDL <3mmol/l are the targets to be sought.

Substantial benefit in lower risk populations by moving from the '5 and 3' target to the '4 and 2' is limited by the shallow slope of the red curve in the figure below.

On average a 1mmol/l reduction in LDL produces a 23 per cent reduction in risk, and a target of '5 and 3' would seem reasonable.

However, this is not the same for higher risk populations. Although there are now data to directly support lipid lowering after a stroke, it is the acute coronary syndrome (ACS) patient who is at highest risk.

In summary, over a two to five year period, aggressive lipid lowering in ACS patients results in 16 per cent risk reduction in death/MI rates.

Lowering to levels of LDL below 2mmol/l appears justified, and it is surprising that the DoH advocate '5 and 3' post-MI.

The evidence base lies with statins and not other classes of drugs. Statins are safer than aspirin and there appears to be no problem with giving aspirin to all patients with a greater than 15 per cent 10-year risk of CVD.

Risk-based prescribing
An approach of using simvastatin 20-40mg for lower risk patients and more potent statins for high-risk patients would seem a good compromise.

Specifying high dosage statin, and no target for high risk patients, may be more feasible than adding more drugs to achieve '4 and 2'.

Just because it is difficult to reach the tough target, it does not mean that we should not try. Asking the patients about compliance is key.

Although a lower cholesterol is better, some statin is certainly better than none.

Dr Malik is consultant cardiologist at St Mary's Hospital NHS Trust and honorary senior lecturer at Imperial College, London

Key points

  • JBS2 and DoH guidelines differ.
  • Acute coronary syndrome patients gain most with statins.
  • Statins appear to have different effects.
  • Lower targets should be introduced for secondary prevention.
  • Simvastatin should be used first line.


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