Efficacy and safety of rosuvastatin 40 mg versus atorvastatin 80 mg in high-risk patients with hypercholesterolemia: results of the POLARIS study.

POLARIS investigated the efficacy and safety of rosuvastatin 40 mg and atorvastatin 80 mg in high-risk patients with hypercholesterolemia. Patients (n=871) were randomized to rosuvastatin 40 mg/day or atorvastatin 80 mg/day for 26 weeks. The primary endpoint was percentage change in LDL-C levels at 8 weeks. Secondary assessments included safety and tolerability, NCEP ATP III LDL-C goal achievement, change in other lipids and lipoproteins at 8 and 26 weeks, and health economics. Mean LDL-C levels were reduced significantly more with rosuvastatin 40 mg than with atorvastatin 80 mg at 8 weeks (-56% versus -52%, p<0.001). The proportion of patients achieving the NCEP ATP III LDL-C goal at 8 weeks was significantly higher in the rosuvastatin 40 mg group (80% versus 72%, p<0.01). Significant differences in the change from baseline in high-density lipoprotein cholesterol (HDL-C) (+9.6% versus +4.4%) and apolipoprotein (Apo)A-I levels (+4.2 versus -0.5) were observed between rosuvastatin and atorvastatin (all p<0.05). Both treatments were well tolerated. Based on a US analysis, rosuvastatin used fewer resources and delivered greater efficacy. Intensive lipid-lowering therapy with rosuvastatin 40 mg/day provided greater LDL-C-lowering efficacy than atorvastatin 80 mg/day, enabling more patients to achieve LDL-C goals. Rosuvastatin may therefore improve LDL-C goal achievement in high-risk patients with hypercholesterolemia.

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.