Efficacy of cholesterol uptake inhibition added to statin therapy among subjects following a low-carbohydrate diet: a randomized controlled trial.
BACKGROUND
Low-carbohydrate diets are frequently used as part of weight-loss programs. These are typically associated with increased fat intake. Therefore, cholesterol absorption inhibition is a logical therapeutic strategy to lower low-density lipoprotein cholesterol (LDL-C) in subjects following a low-carbohydrate diet. However, the efficacy of cholesterol absorption inhibition added to statin therapy has not been studied in this common clinical setting.


METHODS
We performed a randomized controlled trial to compare the effects of ezetimibe on LDL-C when added to simvastatin among subjects following a low-carbohydrate diet. We enrolled 65 subjects who were overweight or obese (body mass index 25-45 kg/m(2)) and had a moderately elevated LDL-C (130-190 mg/dL). During a 4-week diet run-in, subjects were instructed to restrict carbohydrate intake to <30 g/day. Subjects demonstrating adequate adherence to a low-carbohydrate diet (n = 58) were randomized to simvastatin (20 mg) or simvastatin (20 mg) plus ezetimibe (10 mg) for 8 weeks.


RESULTS
Body weight decreased by 3.1% (95% CI 2.1%-4.0%, P < .0001), but the magnitude of weight change did not differ between the groups (P = .92). The LDL-C decreased by 32 mg/dL (95% CI 21-42 mg/dL) in the simvastatin arm and 60 mg/dL (95% CI 45-75 mg/dL) in the combined simvastatin-ezetimibe arm (P = .002). This corresponded to a 20.9% reduction (95% CI 14.5%-27.4%) in LDL-C on simvastatin alone, compared with a 37.4% reduction (95% CI 29.3%-45.6%) on simvastatin-ezetimibe (P = .002). A significant 15.8% reduction in triglycerides was observed among enrolled subjects, which did not differ between the groups.


CONCLUSIONS
Among subjects following a low-carbohydrate diet, combined statin and cholesterol absorption inhibitor therapy is more effective than statin monotherapy for LDL-C lowering.
Chirinos
Julio A
JA
Department of Medicine, University of Pennsylvania and Philadelphia Veterans Affairs Medical Center, USA. julio.chirinos@uphs.upenn.edu
Williams
Monica M
MM
Bregman
David B
DB
Ashfaq
Hera
H
Khayyam
Umar
U
Iqbal
Nayyar
N
D000368:Aged; D000924:Anticholesteremic Agents / Q000008:administration & dosage*; D001384:Azetidines / Q000008:administration & dosage*; D001835:Body Weight; D050528:Diet, Carbohydrate-Restricted; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D000069438:Ezetimibe; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D019821:Simvastatin / Q000008:administration & dosage*; D014280:Triglycerides / Q000097:blood
D000924:Anticholesteremic Agents; D001384:Azetidines; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014280:Triglycerides; D019821:Simvastatin; D000069438:Ezetimibe