Single-drug therapy is often not sufficient to lower total and low-density lipoprotein (LDL) cholesterol levels in patients with familial hypercholesterolemia to desirable or target levels. Therefore, combination drug therapy is often necessary.The most potent therapy to achieve this goal is a combination of a 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitor, which reduces cholesterol synthesis, and a bile acid sequestrant, which indirectly depletes the intrahepatic cholesterol pool. LDL cholesterol reductions reportedly vary between 52 and 54% in short-term trials. Combining a bile acid sequestrant with nicotinic acid reduces LDL cholesterol 34-55% and with a fibrate, 12-42%. The triple-drug regimen of bile acid sequestrant, an HMG CoA reductase inhibitor, and nicotinic acid is even more effective, achieving reductions of 59-67%. All these regimens elevate high-density lipoprotein cholesterol levels concomitantly by 2-37%.