• Timo E Strandberg, John Feely, Emil L Sigurdsson, and DISCOVERY study group.
• Department of Medicine, University of Helsinki, PO Box 340 FIN-00029 HUS, Helsinki, Finland. timo.strandberg@hus.fi
• Clin Ther. 2004 Nov 1;26(11):1821-33.

BackgroundGuidelines for the prevention of coronary heart disease (CHD) advocate reductions in low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) levels as the primary goals. However, approximately 50% to 60% of patients fail to reach recommended cholesterol goals.ObjectivesThe primary objective of this Direct Statin Comparison of LDL-C Values: An Evaluation of Rosuvastatin Therapy Compared with Atorvastatin (DISCOVERY) trial was to compare the efficacy of the 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors rosuvastatin calcium and atorvastatin calcium in achieving the 1998 Second Joint Task Force (JTF) of European and Other Societies on Coronary Prevention target for LDL-C. Secondary objectives included comparing the efficacy of rosuvastatin and atorvastatin in achieving the 1998 JTF-recommended goal for TC and modifying other lipid levels, and to compare the tolerability of the 2 statins.MethodsThis 12-week, randomized, open-label, 2-arm, parallel-group trial was conducted at 210 centers in Finland, Iceland, and Ireland. Patients aged > or =18 years with a high risk for CHD and primary hypercholesterolemia (LDL-C >3.5 mmol/L [>135 mg/dL]) were randomized (2:1) to receive rosuvastatin 10 mg or atorvastatin 10 mg PO OD for 12 weeks. Before randomization, statin-naive patients underwent 6 weeks of dietary counseling, whereas patients receiving treatment with a starting dose of another lipid-lowering therapy but with an LDL-C level >3.1 mmol/L (>120 mg/dL) were switched to study drug immediately after they were determined eligible for the study Patients were assessed for fasting lipid levels at weeks 0 and 12, and the proportions of patients attaining 1998 and 2003 JTF lipid goals (1998: LDL-C, <3.0 mmol/L [<116 mg/dL]; TC, <5.0 mmol/L [<193 mg/dL]; 2003: LDL-C, <2.5 mmol/L [<97 mg/dL]; TC, <4.5 mmol/L [<174 mg/dL]) were calculated. Tolerability was monitored for the 12-week study and for an additional 36-week optional extension period.ResultsOne thousand twenty-four patients were randomized to treatment (568 men, 456 women; mean age, 60.7 years). Patient demographic characteristics were similar between the 2 treatment groups. The efficacy analysis consisted of 911 patients (504 men, 407 women; mean age, 60.7 years; mean body weight, 82.4 kg); 627 received rosuvastatin and 284 received atorvastatin. Compared with atorvastatin, rosuvastatin was associated with significantly greater reductions in LDL-C and TC (both, P < 0.05), and with a significantly greater increase in high-density lipoprotein cholesterol level (P < (105). A greater proportion of patients in the rosuvastatin group compared with the atorvastatin group reached the 1998 goals for LDL-C (83.4% vs 683%; P < 0.001) and TC (76.4% vs 59.5%; P < 0.001). Also, compared with the atorvastatin group, greater proportions of patients in the rosuvastatin group achieved the 2003 JTF goals for LDL-C and TC (both, P < 0.001). Both agents were well tolerated: serious drug-related events were observed in < or =3.0% of patients in each group, and no clinically significant differences were found between the 2 treatment groups.ConclusionsIn this study of selected patients at high risk for CHD and with primary hypercholesterolemia, rosuvastatin 10 mg/d for 12 weeks was associated with significantly greater reductions in LDL-C and TC levels compared with atorvastatin 10 mg/d. Furthermore, significantly more patients receiving rosuvastatin achieved the 1998 and 2003 JTF-recommended lipid targets compared with those receiving atorvastatin. Both agents were well tolerated.

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