The Pharmaceutical Journal
Vol 270 No 7250 p711
24 May 2003

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Combine drugs for high cholesterol

Treatment with both atorvastatin (Lipitor) and ezetimibe (Ezetrol) is significantly better in reducing cholesterol levels than either alone, researchers say.

A study of 628 patients compared ezetimibe (10mg a day), atorvastatin (10, 20, 40 or 80mg a day) and a combination of both (at all doses of atorvastatin).

Co-administration resulted in significantly greater reductions in low density lipoprotein (LDL) cholesterol; a 55 per cent reduction across the pooled groups compared with a 42 per cent reduction for the pooled atorvastatin groups and an 18 per cent reduction in the ezetimibe group.

Combination therapy with the lowest dose of atorvastatin (10mg) achieved similar results to those achieved with the maximum dose of atorvastatin alone (80mg). In these two groups, LDL cholesterol was reduced by 50 and 51 per cent, respectively, and triglycerides by 31 per cent in both groups. A significantly greater increase in high density lipoprotein (HDL) cholesterol was observed in the combination group (9 per cent compared with 3 per cent).

Co-administration of ezetimibe and atorvastatin was well tolerated. The safety profile was similar to that for atorvastatin alone.

The researchers say that the majority of patients do not achieve the recommended LDL cholesterol levels on statins. "Because each doubling of a statin dose provides only 5–6 per cent additional LDL cholesterol reduction, the need for multiple dosage adjustments may limit the routine use of optimum statin doses in clinical practice," they say. "In clinical practice, ezetimibe co-administered with a statin may enable more patients to achieve recommended target LDL cholesterol levels by offering greater LDL cholesterol lowering with fewer dose titrations as well as a well-tolerated alternative for patients in whom maximal dose statin monotherapy in inadequate."

They explain that the benefits appear to come from the different mechanisms of action of these agents. Statins inhibit cholesterol synthesis and ezetimibe inhibits cholesterol absorption across the intestinal wall (Circulation 2003:107:2409).

Ezetimibe has also been shown to be effective when co-administered with simvastatin (PJ, 12 April, p506). It was launched last month (PJ, 26 April, p563).