NEW YORK (Reuters Health) – The combination of the cholesterol uptake inhibitor ezetimibe and a statin is more effective than a statin alone for reducing LDL cholesterol in people on low-carbohydrate diets, randomized trial data show.

Low-carbohydrate diets improve triglycerides and HDL-cholesterol, but not LDL-cholesterol — likely because people eat more protein, dietary cholesterol and fat on this type of diet. Therefore, statins alone are unlikely to lower LDL to optimal levels, clinicians note in the American Heart Journal for May. The addition of a cholesterol absorption inhibitor “represents a logical approach for optimizing LDL-cholesterol lowering in this setting,” they say.

To investigate, Dr. Julio A. Chirinos from the Philadelphia VA Medical Center and colleagues studied 65 adults who were overweight or obese and had moderately elevated LDL (130-190 mg/dL).

During a 4-week diet run-in, subjects were instructed to restrict carbohydrate intake to less than 30 g/day. The 58 subjects who could do this went on to the next phase: the researchers randomly assigned them to simvastatin (20 mg/day) alone or in combination with the cholesterol absorption blocker ezetimibe (10 mg/day) for 8 weeks.

Four of 30 simvastatin-only subjects and 3 of 28 combination therapy subjects dropped out early because they couldn’t tolerate the diet.

After 8 weeks, the mean reduction in LDL was significantly greater with ezetimibe plus simvastatin than with simvastatin alone (60 versus 32 mg/dL). This corresponded to a 37.4% reduction with combination therapy compared with a 20.9% reduction with monotherapy.

The mean reduction in total cholesterol was also greater with combination therapy than with monotherapy (63 vs 35 mg/dL). When expressed as a percentage change, the reductions in total cholesterol were 27.2% and 16.2%, respectively. Changes in non-HDL cholesterol were also significantly greater with combination therapy. Neither group experienced a significant change in HDL cholesterol or triglyceride levels between randomization and the end of the study.

The entire cohort had an overall significant 15.8% reduction in triglyceride level between baseline and the study’s end, with no difference between the groups. Most of this change occurred early in the trial (before randomization), the investigators note.

Study subjects saw an average 3.1% reduction in body weight throughout the trial, with no significant between-group difference in the magnitude of weight change.

Dr. Chirinos and colleagues conclude, “Among patients who follow a low-carbohydrate diet in whom aggressive LDL-cholesterol lowering is required, combined cholesterol synthesis and absorption inhibition appears to be an effective strategy.”

The study was sponsored by Merck/Schering-Plough Pharmaceuticals, maker of ezetimibe (Zetia).

Reference:

Am Heart J 2010;159:918e1-918e6.