Lessons from recent end point trials of lipid-lowering drugs indicate that patients
at very high risk for coronary artery disease (CAD) benefit from treatment that lowers
low-density lipoprotein (LDL) cholesterol plasma levels to ≤1.81 mmol/L (≤70 mg/dL),
that patients with ≥2 risk factors benefit from treatment that lowers plasma LDL cholesterol
to <2.59 mmol/L (<100 mg/dL), and that a significant reduction in CAD event rates
is most often associated with a minimum plasma LDL cholesterol reduction of 30%. Recently,
the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation,
and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) recommendations
were amended to incorporate these lessons. To reach these more aggressive goals and
plasma LDL cholesterol reductions, more aggressive therapies will be required. The
best way to implement more aggressive therapy is to start with one of the more potent
statins, especially atorvastatin or rosuvastatin, or higher doses of other statins.
This approach alone is likely to achieve treatment goals in 50% to 80% of patients.
For patients needing additional plasma LDL cholesterol lowering, combination therapies
will be required. Adding colesevelam, ezetimibe, or niacin to a stable statin regimen
will generally provide an additional 10% to 15% lowering of plasma LDL cholesterol.
These more potent statins, even when used in higher doses, appear to be safe. The
incidence of myopathy and rhabdomyolysis, as documented in long-term clinical trials,
is <0.1% and <0.01%, respectively, except for simvastatin, which has a higher incidence
of these problems. Less information is available about the safety of lowering levels
of plasma LDL cholesterol to ≤1.81 mmol/L (≤70 mg/dL), but an analysis of a recent
2-year-long clinical trial, in which patients had on-treatment plasma LDL cholesterol
levels as low as 0.67 mmol/L (26 mg/dL), reported no signals of untoward effects in
patients with progressively lower levels.
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Published online: June 24, 2005
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© 2005 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
