Comparison of atorvastatin alone versus simvastatin +/- cholestyramine in the management of severe primary hypercholesterolaemia (the six cities study)

Abstract

Background: Atorvastatin is a new member of the class of drugs which inhibit the enzyme Hydroxy-Methylglutaryl Co-A reductase, the rate limiting step in cholesterol biosynthesis.

Aim: To compare the effects of atorvastatin alone versus simvastatin +/- low dose resin (i.e. versus standard care) on low density lipoprotein (LDL) cholesterol in severe primary hypercholesterolaemia.

Methods: An open, multi-centre, randomised study in patients previously stabilised on a cholesterol-lowering diet and simvastatin 40 mg daily, having LDL cholesterol > or = 5.0 mmol/L and triglycerides < 4.0 mmol/L. After five weeks washout, 92 were randomised to receive atorvastatin 10 mg and 44 to receive simvastatin 10 mg. The dose was doubled every six weeks if LDL cholesterol remained > or = 3.5 mmol/L. In accordance with manufacturers' recommendations, maximum dosage was atorvastatin 80 mg daily or simvastatin 40 mg daily (+cholestyramine 4 g daily in 84% of cases). Treatment was continued over 30 weeks. Lipids, lipoproteins, haematological and biochemical safety parameters were measured at regular intervals. Adverse events were monitored.

Results: Baseline LDL cholesterol was approximately 9 +/- 2 mmol/L (SD). After 30 weeks treatment serum cholesterol reduction was 42 +/- 10% on atorvastatin versus 32 +/- 13% on simvastatin +/- resin (p < 0.001), LDL cholesterol reduction 49 +/- 12% versus 38 +/- 14% (p < 0.001), and triglyceride reduction 33 +/- 20% versus 25 +/- 22% (p < 0.02). High density lipoprotein cholesterol increased by 7-10% on both treatments. The proportion of subjects achieving goal LDL cholesterol < 3.5 mmol/L was two to three times greater in those on atorvastatin compared with those on simvastatin +/- resin at each titration point. Six patients on simvastatin and one on atorvastatin were withdrawn. The drugs were generally well tolerated and the pattern of adverse events was similar with either treatment.

Conclusions: Atorvastatin up to 80 mg daily appears to be an effective new treatment for the management of primary hypercholesterolaemia. It shows greater efficacy than simvastatin up to 40 mg daily +/- resin and has a similar safety profile.