Pharmacologic options for aggressive low-density lipoprotein cholesterol lowering: benefits versus risks

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 < or = 1.81 mmol/L (< or = 70 mg/dL), that patients with > or = 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 < or = 1.81 mmol/L (< or = 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.