Further reduction of low-density lipoprotein cholesterol and C-reactive protein with the addition of ezetimibe to maximum-dose rosuvastatin in patients with severe hypercholesterolemia

Background: Patients with severe hypercholesterolemia, including familial hypercholesterolemia, are considered at high risk for coronary artery disease and often prove difficult to treat to current low-density lipoprotein cholesterol (LDL-C) guidelines. Methods: In this open-label, 12-week substudy within a larger trial, ezetimibe 10 mg was added to stable therapy with rosuvastatin 40 mg (± bile acid sequestrant/niacin) in 107 patients with severe hypercholesterolemia who had not achieved LDL-C goal of <100 mg/dL. Results: Prior to the start of rosuvastatin treatment, on diet alone, mean LDL-C levels were 291 ± 59 mg/dL and decreased to 141 ± 30 mg/dL on rosuvastatin 40 mg daily at the substudy baseline prior to ezetimibe. After 12 weeks, the addition of ezetimibe produced an additional 15% ±9% reduction in LDL-C (P < 0.001) compared to pre-rosuvastatin levels and a mean LDL-C of 103 ± 27 mg/dL, resulting in 59% of patients reaching their LDL-C goals. The combination reduced LDL-C by 65% ± 9% from diet alone. Combination with ezetimibe also produced significant additional percent reductions in non-high-density lipoprotein (14%), apolipoprotein B (10%), and triglycerides (6%). Median C-reactive protein was reduced 54% (P < 0.001) by the combination compared with diet alone, a further incremental reduction of 13% (P < 0.001) with the addition of ezetimibe. The combination was well tolerated, with no patients developing myopathy or clinically significant elevations of creatine kinase or transaminases. Conclusions: The combination of rosuvastatin 40 mg and ezetimibe 10 mg offers the most effective LDL-C-lowering therapy yet reported, and is helpful in achieving lipid goals and reducing C-reactive protein levels in high-risk patients with severe hypercholesterolemia, including familial hypercholesterolemia.