Background: Dysbetalipoproteinemia is an uncommon genetic disorder characterized by accumulation of plasma remnant lipoproteins, severe mixed dyslipidemia, elevated apolipoprotein E levels, accelerated atherosclerosis, and premature cardiovascular disease.
Objective: To evaluate the efficacy and safety of rosuvastatin in patients with dysbetalipoproteinemia.
Methods: Following a 6-week washout, 32 patients with dysbetalipoproteinemia received rosuvastatin 10 mg, rosuvastatin 20 mg, and pravastatin 40 mg, each for 6 weeks in a randomized, double-blind, three-way crossover design. Patients subsequently entered an 18-week open-label phase in which the rosuvastatin dosage could be increased from 20 mg to a maximum of 40 mg at 6 weekly intervals to reach National Cholesterol Education Program goals for non-high-density lipoprotein cholesterol (non-HDL-C) and optimal triglyceride (TG). Fibrates (except gemfibrozil) could be added if patients were not at goal on rosuvastatin 40 mg. The primary efficacy variable was percent change from baseline in non-HDL-C during the double-blind phase. The prespecified efficacy criterion was for the 95% confidence interval (CI) of non-HDL-C to lie entirely below -25% for any rosuvastatin dose.
Results: Following drug washout, median total cholesterol was 8.86 mmol/L, non-HDL-C 7.61 mmol/L, and TG 5.69 mmol/L. After 6-week treatment, median change in non-HDL-C was -48.2% (95% CI -56.7% to -45.6%) for rosuvastatin 10 mg, -56.4% (95% CI -61.4% to -48.5%) for rosuvastatin 20 mg, and -35.1% (95% CI -41.6% to -29.6%) for pravastatin 40 mg. Rosuvastatin increased HDL-C and apolipoprotein A-I and substantially reduced total, very low-, intermediate-, and low-density lipoprotein cholesterol and TG, and corresponding apolipoproteins. Efficacy was maintained in the open-label phase, with reduction in non-HDL-C of -61.5%, -62.8% and -65.8% at weeks 24, 30 and 36, respectively. All treatments were well tolerated.
Conclusion: Rosuvastatin 10 and 20 mg favorably modify the dyslipidemia of patients with dysbetalipoproteinemia.