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

BackgroundPatients 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.MethodsIn 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.ResultsPrior 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.ConclusionsThe 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.