How Low Should We Go on LDL?

source: http://www.medscape.com/viewarticle/551989?src=mp

These days, even most laypersons know that low-density lipoprotein (LDL) cholesterol is the "bad" cholesterol and that the class of drugs known as statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) is a proven treatment for patients with elevated levels of serum LDL cholesterol. For the physician, this guideline-mandated, evidence-based treatment strategy is supported by the results of numerous large, randomized, placebo-controlled clinical trials,[1-6] which have demonstrated highly significant reductions in the risk of death or cardiovascular events in populations with (secondary prevention) or without (primary prevention) a history of coronary artery disease (CAD).

The 2003 National Cholesterol Education Program guidelines recommended that patients with established CAD or diabetes (sometimes called a "CAD equivalent") should be treated to reach a target LDL cholesterol level < 100 mg/dL.In demonstrating their protection against future events, these first placebo-controlled statin trials employed standard doses to reduce LDL cholesterol levels by 25% to 35%. In other words, large reductions in LDL cholesterol can be achieved, and the guidelines set a target level -- do we have a final answer on how to treat our CAD (and diabetic) patients?

While statins have been proven over the last decade to be among the safest and most efficacious drugs in the physician's armamentarium, these historic results have still left some remaining questions:

* What LDL level should be the threshold for initiating statin treatment?

* What kind of reductions, with what kind of benefit, have subsequent trials with more potent ("second generation") statins and/or higher doses of the first-generation statins demonstrated?

* How low can/should LDL cholesterol be lowered? Is there a "J" curve, below which the risk outweighs the benefits with the more intensive statin dosing?