Pitavastatin and Atorvastatin double-blind randomized comPArative study among hiGh-risk patients, including thOse with Type 2 diabetes mellitus, in Taiwan (PAPAGO-T Study)

Abstract

Background: Evidence about the efficacy and safety of statin treatment in high-risk patients with hypercholesterolemia is available for some populations, but not for ethnic Chinese. To test the hypothesis that treatment with pitavastatin (2 mg/day) is not inferior to treatment with atorvastatin (10 mg/day) for reducing low-density lipoprotein cholesterol (LDL-C), a 12-week multicenter collaborative randomized parallel-group comparative study of high-risk ethnic Chinese patients with hypercholesterolemia was conducted in Taiwan. In addition, the effects on other lipid parameters, inflammatory markers, insulin-resistance-associated biomarkers and safety were evaluated.

Methods and results: Between July 2011 and April 2012, 251 patients were screened, 225 (mean age: 58.7 ± 8.6; women 38.2% [86/225]) were randomized and treated with pitavastatin (n = 112) or atorvastatin (n = 113) for 12 weeks. Baseline characteristics in both groups were similar, but after 12 weeks of treatment, LDL-C levels were significantly lower: pitavastatin group = -35.0 ± 14.1% and atorvastatin group = -38.4 ± 12.8% (both: p < 0.001). For the subgroup with diabetes mellitus (DM) (n = 125), LDL-C levels (-37.1 ± 12.9% vs. -38.0 ± 13.1%, p = 0.62) were similarly lowered after either pitavastatin (n = 63) or atorvastatin (n = 62) treatment. Triglycerides, non-high density lipoprotein cholesterol, and apoprotein B were similarly and significantly lower in both treatment groups. In non-lipid profiles, HOMA-IR and insulin levels were higher to a similar degree in both statin groups. Hemoglobin A1C was significantly (p = 0.001) higher in the atorvastatin group but not in the pitavastatin group. Both statins were well tolerated, and both groups had a similar low incidence of treatment-emergent adverse events.

Conclusion: Both pitavastatin (2 mg/day) and atorvastatin (10 mg/day) were well tolerated, lowered LDL-C, and improved the lipid profile to a comparable degree in high-risk Taiwanese patients with hypercholesterolemia.

Trial registration: ClinicalTrials.gov NCT01386853 http://clinicaltrials.gov/ct2/show/NCT01386853?term=NCT01386853&rank=1.

Figure 1. Enrollment and consort of study participants treated with pitavastatin or atorvastatin.

Figure 2. Changes in lipid profiles before and after 12 weeks of treatment with pitavastatin (PTV) (2 mg) or atorvastatin (ATV) (10 mg).

There is no significant difference in the percentage change of low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), triglyceride (TG), non-HDL-C, apolipoprotein A1 (Apo A1), or apolipoprotein B (Apo B) levels from baseline, between the PTV and ATV groups. Both statins similarly but significantly reduced LDL-C levels after 12 weeks of treatment. PTV and ATV significantly reduced TG, non-HDL-C, and Apo B; the percentage changes were not significantly different.

Figure 3. Subgroup analysis comparing the percentage of participants with final LDL-C level < 100 mg/dL after 12 weeks of either pitavastatin (2 mg) or atorvastatin (10 mg) treatment.

Continuous variables are means ± SD. ADMA = asymmetric dimethylarginine; ALT = alanine aminotransferase; Apo A1 = apolipoprotein A1; Apo B = apolipoprotein B; AST = aspartate transaminase; BMI = body mass index; BUN = blood urea nitrogen; CPK = creatine phosphokinase; CRP = C-reactive protein; DM = Diabetes mellitus; Gamma GT = gamma-glutamyl transpeptidase; HDL-C = high-density lipoprotein cholesterol; HOMA-IR = homeostatic model assessment-insulin resistance; LDH = lactate dehydrogenase; LDL-C = low-density lipoprotein cholesterol; TG = triglyceride.