Comparative efficacy of pitavastatin and simvastatin in high-risk patients: a randomized controlled trial.

Introduction: Despite the proven efficacy of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) in lowering total and low-density lipoprotein cholesterol (LDL-C), many patients do not reach recommended lipid targets. This study compared pitavastatin, a new and highly effective statin, and simvastatin in patients at high risk of coronary heart disease (CHD). The primary objective was to demonstrate noninferiority of pitavastatin to simvastatin.

Methods: The study was a phase 3, randomized, double-blind, double-dummy, parallel-group, active-controlled study conducted at 37 centers in five European countries. Following a dietary run-in period of 6-8 weeks, patients with primary hypercholesterolemia or combined dyslipidemia and at least two CHD risk factors were randomized 2:1 to receive pitavastatin 4 mg or simvastatin 40 mg once daily for 12 weeks. The primary efficacy variable was the change in LDL-C from baseline.

Results: In total, 355 patients were randomized, 236 to pitavastatin and 119 to simvastatin; 330 patients (223 and 107, respectively) completed the study. In the pitavastatin group, mean (± SD) reduction in LDL-C concentrations from baseline was -44.0 ± 12.8% compared with -43.8 ± 14.4% in the simvastatin group. The adjusted mean treatment difference (simvastatin--pitavastatin) was 0.31% (95% confidence interval -2.47, 3.09; P = 0.829), which was within the predefined noninferiority range. More than 80% of patients in each group reached recommended LDL-C targets. Pitavastatin provided a greater increase in high-density lipoprotein cholesterol (HDL-C; 6.8% vs. 4.5%; P = 0.083) and a significantly greater decrease in triglycerides (-19.8% vs. -14.8%; P = 0.044) than simvastatin. Both treatments were well tolerated.

Conclusion: Pitavastatin 4 mg is as effective as simvastatin 40 mg in lowering LDL-C in dyslipidemic patients at high risk of CHD, with additional effects on HDL-C and triglycerides. Therefore, pitavastatin may be appropriate for the management of dyslipidemic patients at high cardiovascular risk.