Drug Therapy to Lower Cholesterol

Cholesterol lowering can be achieved in many ways. The first choice is always lifestyle modification with diet and exercise. A regular exercise program will raise the protective cholesterol (HDL) and lower the harmful cholesterol (LDL) while decreasing the fats (triglycerides) in the blood. In patients that don't meet the goal cholesterol level of HDL above 35 mg/dl or LDL less than 130 mg/dl, medical therapy is the next step. For patients that have suffered a vascular event such as stroke, heart attack or revascularization procedure (stent or bypass surgery) treatment with medications is indicated regardless of the cholesterol level. The goal LDL level for high-risk patients (previous heart attack, history of diabetes or history of peripheral arterial disease) mandated below 100 mg/dl but most physicians ascribe to data that suggests a goal LDL less than 80 mg/dl is probably better.
Statins are considered the cornerstone of medical therapy to lower cholesterol. The statins commonly used are rosuvastatin (Crestor), atorvastatin (Lipitor), simvastatin (Zocor), pravastatin (Pravachol) and lovastatin (Mevacor). Crestor is considered the most potent statin and has been shown to be effective in the reduction of vascular events and reduction in mortality patients with normal cholesterol levels (JUPITER, "New England Journal of Medicine," Nov. 20, 2008). All the other statins have been shown to be effective in the secondary prevention of heart attack, stroke and reduction in cardiovascular mortality in patients with heart attack.
The statins work by inhibiting the HMG-coA-reductase enzyme. This enzyme catalyzes the chemical reaction in the liver that forms lipids in the blood. The effect of statins in reducing cholesterol is clear but their other actions of statins such an anti-inflammatory effect and even a weak anti-arrhythmic effect can be beneficial in patients with vascular disease. Side effects of statins include elevation of liver enzymes and muscle weakness (which is rare but can be serious)
Other key agents used to reduce cholesterol include bile acid sequestrants (cholestyramine), fibrates (fenofibrate, gemfibrozil), niacin and ezetimibe (Zetia). These other agents are all effective in specific subsets of patients and have evidence for their use but are second line to statins in patients with a history of heart attack.
Bile acid sequestrants trap cholesterol in the gastrointestinal tract and secrete out of the body. Side effects include abdominal bloating, cramps and diarrhea. Fibrates work via multiple pathways such as increased clearance of cholesterol and triglycerides. Fibrates generally have low side effects but some patients will have gastrointestinal complaints. Niacin is very effective at raising the HDL and lowering the HDL, but is often limited by its side effects of flushing. Ezetimibe works by decreasing absorption of cholesterol in the gastrointestinal tract. It has a very low side effect profile, but has been much maligned lately in the combination medication Vytorin (a combination of ezetimibe and simvastain). The two drugs together are very effective in reducing cholesterol, but there is still no conclusive data that it is effective in preventing vascular events in high- or low-risk patients. Studies are underway that will provide an answer.
In patients that require medications to lower cholesterol, it is often better to consider that these medications are not just to lower the cholesterol but are actually a "heart pill." These medications should be viewed not as treatments for cholesterol but as treatments for heart disease and as a way to prevent another vascular event or death from vascular causes.