Combination Drug Therapy with HMG CoA Reductase Inhibitors and Bile Acid Sequestrants for Hypercholesterolemia

Abstract

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%.

Forecasting Patient Outcomes in the Management of Hyperlipidemia

“…When combination therapy is required for lipid lowering, the LDL reduction with drug therapy is additive within normal dosing ranges. 21,35,36,[45][46][47][48][49][50][51]63,73,78,88,91,[94][95][96][97][98] For example, 20 mg of fluvastatin provides an approximate 20% LDL reduction as monotherapy. 36,[45][46][47][48][49][50][51][52][53][54][55] Niacin, 3 g, provides an approximate 21% LDL reduction as monotherapy.…”

Lipid-Lowering Drugs Acting at the Level of the Gastrointestinal Tract

“…Generally, low-dose combinations lead to greater or similar LDL-C reductions compared with high dose statin monotherapy and are safe and well tolerated [30,32,[99][100][101][102][103][104][105][106][107][108][109][110][111][112][113]. Lovastatin 20 mg/d plus colestipol 10 g/d produced greater reductions in LDL-C than lovastatin 40 mg/d monotherapy [114].…”

HMG-CoA Reductase Inhibitor Use in the Aged

“…Addition of a bile acid sequestrating resin has been shown to be the safest and most effective combination, reducing LDL cholesterol by up to 60% (Erkelens 1990;Leren et al 1988). Further reductions in LDL cholesterol of 6 to 25% beyond those achieved with monotherapy have been reported with combined lovastatin-gemfibrozil therapy (East et al 1988;Glueck et al 1990;Illingworth & Bacon 1989), and of 20% with combined simvastatin-bezafibrate therapy (Lintott et al 1991a).…”