A 52-Week, Randomized, Open-Label, Parallel-Group Comparison of the Tolerability and Effects of Pitavastatin and Atorvastatin on High-Density Lipoprotein Cholesterol Levels and Glucose Metabolism in Japanese Patients with Elevated Levels of Low-Density Lipoprotein Cholesterol and Glucose Intolerance

Abstract

Background: Statin therapy has been found to produce substantial reductions in low-density lipoprotein cholesterol (LDL-C) levels, resulting in a reduced risk for cardiovascular events. Recently, research interest has focused on modification of high-density lipoprotein cholesterol (HDL-C) levels for the potential prevention of cardiovascular events. The effects of pitavastatin and atorvastatin on HDL-C have not been directly compared. Objectives: This study compared the effects of pitavastatin and atorvastatin on HDL-C and other lipids and glucose metabolism in Japanese patients with elevated LDL-C levels and glucose intolerance. The tolerability of the 2 treatments was also compared. Methods: This was a multicenter, open-label, parallelgroup trial. Patients with LDL-C levels ≥ 140 mg/dL and glucose intolerance (defined according to Japanese criteria for borderline diabetes and World Health Organization criteria for impaired fasting glucose and impaired glucose tolerance) were randomly assigned to receive either pitavastatin 2 mg/d or atorvastatin 10 mg/d for 52 weeks. Levels of serum lipids and lipoproteins and measures of glucose metabolism (fasting insulin, fasting glucose, glycosylated hemoglobin, and homeostasis model assessment for insulin resistance) were obtained at baseline and at 8, 26, and 52 weeks of treatment. The effect of study drug on glucose metabolism was evaluated as a tolerability outcome. Tolerability was further assessed based on adverse events, either spontaneously reported or elicited by questioning; physical examination findings; and clinical laboratory test results. Study physicians rated the relationship of adverse events to study medication as unrelated, suspected, or probable. Results: Two hundred seven patients were enrolled in the study, and efficacy was evaluated in 173 patients (88 pitavastatin, 85 atorvastatin). Thirty-four patients were excluded for reasons including failure to start medication or lack of ≥ 6 months of follow-up. Women accounted for 62% (108/173) of the evaluable population, which had a mean age of 63.3 years and a mean weight of 63.0 kg; 89% (154/173) had diabetes mellitus. The percent change in HDL-C levels was significantly greater in the pitavastatin group compared with the atorvastatin group (8.2 vs 2.9, respectively; P = 0.031), as was the percent change in apolipoprotein (Apo) A-I (5.1 vs 0.6; P = 0.019). The percent change in LDL-C levels was significantly lower with atorvastatin compared with pitavastatin (−40.1 vs −33.0, respectively; P = 0.002), as were the percent changes in non-HDL-C (−37.4 vs −31.1; P = 0.004), Apo B (−35.1 vs −28.2; P < 0.001), and Apo E (−28.1 vs −17.8; P < 0.001). The significant results for these parameters were unchanged when all 189 subjects who received ≥ 1 dose of study medication were included in the analysis, using last-value-carried-forward methodology. There were no significant differences between treatments with respect to the measures of glucose metabolism. Both statins appeared to be well tolerated. Adverse events occurred in 9% (9/96) of the pitavastatin group and 14% (13/93) of the atorvastatin group ( P = NS). Two patients in the pitavastatin group and none in the atorvastatin group had an alanine aminotransferase value >3 times the upper limit of normal ( P = NS). Conclusions: In these patients with elevated LDL-C levels and glucose intolerance, 52 weeks of treatment with pitavastatin 2 mg/d was associated with significantly greater increases in HDL-C and Apo A-I levels than atorvastatin 10 mg/d. Both treatments were well tolerated.