Key result
Pitavastatin 2 mg daily significantly increased circulating CD34+KDR+ endothelial progenitor cells (from 0.021% to 0.054%, p<0.05) and plasma VEGF levels in high-risk patients, whereas atorvastatin 10 mg did not.
Why the study?
Does pitavastatin improve circulating endothelial progenitor cells and vascular endothelial growth factor compared to atorvastatin in high-risk patients with hypercholesterolemia?
RCT (n=26)
Double-blind
1:1
No
Does pitavastatin improve circulating endothelial progenitor cells and vascular endothelial growth factor compared to atorvastatin in high-risk patients with hypercholesterolemia?
Absolute Event Rate: 0.054% vs 0.043%
p-value: p=<0.05
Pitavastatin, but not atorvastatin, increases circulating endothelial progenitor cells and VEGF levels in high-risk patients, suggesting differential pleiotropic vascular effects among statins.
Pitavastatin may confer unique endothelial benefits versus atorvastatin in high-risk hypercholesterolemia; extends evidence for differential statin pleiotropy on vascular repair.
BACKGROUND: Circulating endothelial progenitor cells (EPCs) reflect endothelial repair capacity and may be a significant marker for the clinical outcomes of cardiovascular disease. While some high-dose statin treatments may improve endothelial function, it is not known whether different statins may have similar effects on EPCs.This study aimed to investigate the potential class effects of different statin treatment including pitavastatin and atorvastatin on circulating EPCs in clinical setting. METHODS: A pilot prospective, double-blind, randomized study was conducted to evaluate the ordinary dose of pitavastatin (2 mg daily) or atorvastatin (10 mg daily) treatment for 12 weeks on circulating EPCs in patients with cardiovascular risk such as hypercholesterolemia and type 2 diabetes mellitus (T2DM). Additional in vitro study was conducted to clarify the direct effects of both statins on EPCs from the patients. RESULTS: A total of 26 patients (19 with T2DM) completed the study. While the lipid-lowering effects were similar in both treatments, the counts of circulating CD34+KDR+EPCs were significantly increased (from 0.021 ± 0.015 to 0.054 ± 0.044% of gated mononuclear cells, P < 0.05) only by pitavastatin treatment. Besides, plasma asymmetric dimethylarginine level was reduced (from 0.68 ± 0.10 to 0.53 ± 0.12 μmol/L, P < 0.05) by atorvastatin, and plasma vascular endothelial growth factor (VEGF) level was increased (from 74.33 ± 32.26 to 98.65 ± 46.64 pg/mL, P < 0.05) by pitavastatin. In the in vitro study, while both statins increased endothelial nitric oxide synthase (eNOS) expression, only pitavastatin increased the phosphorylation of eNOS in EPCs. Pitavastatin but not atorvastatin ameliorated the adhesion ability of early EPCs and the migration and tube formation capacities of late EPCs. CONCLUSIONS: While both statins similarly reduced plasma lipids, only pitavastatin increased plasma VEGF level and circulating EPCs in high-risk patients, which is probably related to the differential pleiotropic effects of different statins. TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov, NCT01386853.
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Lin et al. (2014) conducted an RCT in Hypercholesterolemia and high cardiovascular risk (predominantly Type 2 Diabetes Mellitus) (n=26). Pitavastatin vs. Atorvastatin 10 mg daily was evaluated on Circulating CD34+KDR+ endothelial progenitor cells (EPCs) as a percentage of gated mononuclear cells (p=<0.05). Pitavastatin 2 mg daily significantly increased circulating CD34+KDR+ endothelial progenitor cells (from 0.021% to 0.054%, p<0.05) and plasma VEGF levels in high-risk patients, whereas atorvastatin 10 mg did not.
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