Studies have shown that lowering low-density lipoprotein (LDL) cholesterol levels helps to prevent coronary artery disease (CAD). The 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, commonly known as statins, are the agents most effective in lowering LDL cholesterol. Patients at the highest risk for CAD morbidity and mortality are the major beneficiaries of LDL cholesterol reduction. Treatment guidelines, such as those recommended by the National Cholesterol Education Program (NCEP), recommend tight control of high-risk patients using statin therapy. Stein reviewed the current methods of managing dyslipidemia, most notably to reduce LDL cholesterol, in high-risk patients.
The latest NCEP guidelines are noted in the accompanying table. Recommendations from the American Diabetes Association set an optimal LDL cholesterol treatment goal for adults with diabetes at less than 100 mg per dL (2.60 mmol per L). Of the statins currently available, lovastatin is the only one manufactured as a generic product. These agents reduce LDL cholesterol levels by about 55 percent at the highest dosages. Atorvastatin is the most potent LDL cholesterol-lowering statin drug, followed by pravastatin and fluvastatin, and then lovastatin and simvastatin. Administration of higher dosages of these agents is limited by increases in liver or muscle toxicity. The most common side effects are myalgias and myocytis. Rhabdomyolysis is rare. Because there appears to be a correlation between initial statin dosage and efficacy, and maintenance of the LDL cholesterol goal after one year, the initial dosage should be one that is most likely to be efficacious; titration upward, when indicated, should occur rapidly until the LDL cholesterol goal is achieved.
Bile acid sequestrants act in the gut by preventing the enterohepatic recycling of bile acids and depleting cholesterol stores in the liver, and they are less effective than statins in lowering LDL cholesterol levels. Dosing is limited by gastrointestinal side effects of gas, bloating, and constipation. LDL cholesterol reduction is rarely greater than 15 to 25 percent, but bile acid sequestrants are useful in combination with statins to achieve greater LDL cholesterol reductions.
Niacin can reduce LDL cholesterol levels by 10 to 20 percent at dosages of 1,500 to 4,500 mg per day. It is also the most effective agent for increasing high-density lipoprotein (HDL) cholesterol levels. The initial adverse effects (flushing and skin irritation in the neck and face) can be overcome by reassurance, rapid dosage escalation, and taking the medication with food and low-dose aspirin. In rare cases, higher dosages may cause hepatitis, gout, or hyperglycemia. The new sustained-release formulation of niacin, which is taken once-daily at bedtime, reduces bothersome initial adverse effects. Niacin can be used in combination with statins, and a fixed-dose combination of lovastatin and long-acting niacin has recently been approved by the U.S. Food and Drug Administration (FDA). Plant stanols can decrease LDL cholesterol levels by about 10 percent in patients with modestly elevated levels. These compounds, which are included in stanol-containing margarines, are well tolerated and useful taken in combination with statins.
Combination therapy with a statin is common and can assist patients in reaching their LDL cholesterol goal. The first agent to consider using in combination with a statin is a bile acid sequestrant because of the decreased risk of increased statin side effects. The combination of a statin with niacin can yield a decrease in LDL cholesterol and triglyceride levels as well as an increase in HDL cholesterol levels. New statins with a greater ability to decrease LDL cholesterol levels and increase HDL cholesterol levels are in development, as are newer bile acid sequestrants. Cholesterol absorption inhibitors are also being developed but are not yet available.
The authors conclude that patients at high risk for CAD should be treated aggressively for dyslipidemia. Treatment combinations can be useful to achieve target levels.