Comparison of pitavastatin with simvastatin in primary hypercholesterolaemia or combined dyslipidaemia

Abstract

Objectives:

The primary objective of this study was to demonstrate equivalence of pitavastatin compared with simvastatin in the reduction of low-density lipoprotein cholesterol (LDL-C) levels in patients with primary hypercholesterolaemia or combined dyslipidaemia. Secondary objectives included achievement of National Cholesterol Education Program Adult Treatment Panel (NECP) and European Atherosclerosis Society (EAS) LDL-C goals, comparison of other lipid parameters, and assessment of safety and tolerability of the two statins.

Research design and methods:

A prospective, randomised, active-controlled double-blind, double-dummy, 12-week therapy trial was conducted in 857 patients with either primary hypercholesterolaemia or combined dyslipidaemia. The trial was designed to demonstrate the equivalence (non-inferiority of presumed equipotent doses) of pitavastatin compared with simvastatin. Patients were randomised to one of four groups: pitavastatin 2 mg/day, pitavastatin 4 mg/day, simvastatin 20 mg/day or simvastatin 40 mg/day. The main study limitation was restriction of the study population to those eligible for administration of simvastatin.

Trial registration:

This clinical trial has been registered at www.clinicaltrials.gov NCT# NCT00309777.

Results:

Pitavastatin 2 mg showed significantly better reductions of LDL-C (p = 0.014), non-high-density lipoprotein cholesterol (non-HDL-C) (p = 0.021) and total cholesterol (TC) (p = 0.041) compared with simvastatin 20 mg and led to more patients achieving the EAS LDL-C treatment target. Reduction of LDL-C in the pitavastatin 2 mg group was 39% compared with 35% in the simvastatin 20 mg group. Pitavastatin 4 mg showed similar effects on all lipid parameters to simvastatin 40 mg. The reductions in LDL-C were 44% and 43%, respectively. The safety profiles of pitavastatin and simvastatin were similar at the two dose levels. Pitavastatin was considered superior to simvastatin in terms of percent reduction of LDL-C in the lower dose group comparison and proved to be equivalent to simvastatin in percent reduction of LDL-C in the higher-dose group.

Conclusion:

As compared with simvastatin, an established first-line lipid-lowering agent, pitavastatin is an efficacious treatment choice in patients with primary hypercholesterolaemia or combined dyslipidaemia.

Keywords::

• Dyslipidaemia
• Hypercholesterolaemia
• Pitavastatin
• Simvastatin
• Statins

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Erratum

Transparency

Declaration of funding

The trial was sponsored by Kowa Research Europe Ltd who contracted PharmaNet to provide support for the study, including statistical analysis. All authors were involved in at least one of the following: conception, design, acquisition, analysis, statistical analysis, interpretation of data, drafting the manuscript and/or revising the manuscript for important intellectual content. All authors approved the final version to be published.

Declaration of financial / other relationships

L.O. has disclosed that he has received research grant funding from Merck, Pfizer, Schering-Plough, Roche and Boehringer; that he is a consultant/advisor to Kowa; and that he has received speakers’ bureaux fees from AstraZeneca and Kowa. D.B. and N.H are employees of Kowa Research Europe Ltd. V.A. is an employee of PharmaNet Ltd

Acknowledgments

Statistical analysis was provided by the Biostatistics Department at PharmaNet. The authors thank Susan Aldridge (Aldridge Associates Ltd) for help in preparation of this manuscript, and all participating researchers, clinicians, healthcare professionals, personnel and patients who helped to complete the trial.