A 52-week, multicenter, randomized, parallel-group, double-blind, double-dummy study to assess the efficacy of atorvastatin and simvastatin in reaching low-density lipoprotein cholesterol and triglyceride targets:: The treat-to-target (3T) study

Background: Guidelines for the prevention of coronary heart disease call for low-density lipoprotein cholesterol (LDL-C) reduction as the primary target of treatment and reduction of triglycerides (TG) as an additional target. Objective: The purpose of this study was to investigate the ability of atorvastatin and simvastatin to reduce LDL-C and TG concentrations and to meet 3 target lipid levels: LDL-C less than or equal to2.6 mmol/L; TG less than or equal to1.5 mmol/L; and both LDL-C less than or equal to2.6 mmol/L and TG less than or equal to1.5 mmol/L. Methods: The Treat-to-Target (3T) Study was a 52-week, multicenter, randomized, parallel-group study. Using the double-blind, double-dummy technique, adult patients aged 35 to 75 years with cardiovascular disease and dyslipidemia, defined as LDL-C concentration less than or equal to4.0 mmol/L (greater than or equal to155 mg/dL), were randomised in a 1:1 ratio to receive once-daily oral treatment with 20 mg atorvastatin or 20 mg simvastatin. Fasting (12-hour) blood samples for the estimation of lipid levels and clinical laboratory values were collected after 4, 8, 12, 26, and 52 weeks. The dose was doubled after 12 weeks if the target National Cholesterol Education Program level of LDL-C (less than or equal to2.6 mmol/L [100 mg/dL]) was not reached at 8 weeks. Results: The intent-to-treat analysis included 552 patients (418 men, 134 women) randomized to receive atorvastatin and 535 (404 men, 131 women) randomized to receive simvastatin. The number of patients enrolled in the study allowed the evaluation of the drugs' effects on TG. Patient demographic characteristics were similar for the 2 treatment groups, and there were no differences in baseline lipid values. Compared with simvastatin, atorvastatin produced significantly greater reductions in LDL-C (8 weeks: -46% vs -40%, P < 0.001; 52 weeks: -49% vs -44%, P < 0.001) and in TG (8 weeks: -23% vs -14%, P < 0.001; 52 weeks: -24% vs -16%, P < 0.001). Compared with simvastatin-treated patients, a significantly greater number of atorvastatin-treated patients reached the LDL-C target after 8 weeks (45% vs 24%; P < 0.001). Fewer atorvastatin patients needed to have their dose doubled; nevertheless more atorvastatin patients reached the LDL-C target after 52 weeks (61% vs 41%; P < 0.001). Both statins were well tolerated. Muscular symptoms occurred in 12 patients (2.2%) in the atorvastatin group and in 13 patients (2.4%) in the simvastatin group. Conclusions: Atorvastatin 20 or 40 mg/d for up to 1 year of treatment was significantly more effective than simvastatin 20 or 40 mg/d in reducing LDL-C and TG levels and at achieving recommended lipid targets in this selected patient population with cardiovascular disease and dyslipidemia. Both statins were well tolerated. Copyright (C) 2003 Excerpta Medica, Inc.