TY - JOUR T1 - Achieving lipoprotein goals in patients at high risk with severe hypercholesterolemia: efficacy and safety of ezetimibe co-administered with atorvastatin. AU - Stein,Evan, AU - Stender,Steen, AU - Mata,Pedro, AU - Sager,Philip, AU - Ponsonnet,Damien, AU - Melani,Lorenzo, AU - Lipka,Leslie, AU - Suresh,Ramachandran, AU - Maccubbin,Darbie, AU - Veltri,Enrico, AU - ,, PY - 2004/9/25/pubmed PY - 2004/12/17/medline PY - 2004/9/25/entrez SP - 447 EP - 55 JF - American heart journal JO - Am Heart J VL - 148 IS - 3 N2 - BACKGROUND: Despite the efficacy of statins in lowering low-density lipoprotein cholesterol (LDL-C) levels, many patients who are at high risk for heart disease with hypercholesterolemia require additional LDL-C level reduction. The cholesterol absorption inhibitor, ezetimibe, has been shown to provide significant incremental reductions in LDL-C levels when co-administered with statins. This study was performed to compare the efficacy and safety of ezetimibe (10 mg) plus response-based atorvastatin titration versus response-based atorvastatin titration alone in the attainment of LDL-C goals in subjects who are at high risk for coronary heart disease (CHD) and are not at their LDL-C goal on the starting dose of atorvastatin. METHODS: This was a 14-week, multicenter, randomized, double-blind, active-controlled study conducted in 113 clinical research centers in 21 countries. Participants were adults with heterozygous familial hypercholesterolemia (HeFH), CHD, or multiple (> or =2) cardiovascular risk factors, and a LDL-C level > or =130 mg/dL after a 6- to 10-week dietary stabilization and atorvastatin (10 mg/day) open-label run-in period. Eligible subjects continued to receive atorvastatin (10 mg) and were randomized to receive blinded treatment with ezetimibe (10 mg/day; n = 305) or an additional 10 mg/day of atorvastatin (n = 316). The atorvastatin dose in both groups was doubled after 4 weeks, 9 weeks, or both when the LDL-C level was not at its goal (< or =100 mg/dL), so that patients receiving combined therapy could reach 40 mg/day and patients receiving atorvastatin alone could reach 80 mg/day. The primary end point was the proportion of subjects achieving their LDL-C level goal at week 14. A secondary end point was the change in LDL-C level and other lipid parameters at 4 weeks after ezetimibe co-administration with 10 mg/day of atorvastatin versus 20 mg/day of atorvastatin monotherapy. RESULTS: The proportion of subjects reaching their target LDL-C level goal of < or =100 mg/dL was significantly higher in the co-administration group than in the atorvastatin monotherapy group (22% vs 7%; P <.01). At 4 weeks, levels of LDL-C, triglycerides, and non-high-density lipoprotein cholesterol were reduced significantly more by combination therapy than by doubling the dose of atorvastatin (LDL-C -22.8% versus -8.6%; P <.01). The combination regimen had a safety and tolerability profile similar to that of atorvastatin alone. CONCLUSIONS: The addition of ezetimibe to the starting dose of 10 mg/day of atorvastatin followed by response-based atorvastatin dose titration to a maximum of 40 mg/day provides a more effective means for reducing LDL-C levels in patients at high risk for CHD than continued doubling of atorvastatin as high as 80 mg/day alone. SN - 1097-6744 UR - https://www.unboundmedicine.com/medline/citation/15389231/Achieving_lipoprotein_goals_in_patients_at_high_risk_with_severe_hypercholesterolemia:_efficacy_and_safety_of_ezetimibe_co_administered_with_atorvastatin_ DB - PRIME DP - Unbound Medicine ER -