Original Article

The effects of additional ezetimibe treatment to baseline rosuvastatin on circulating PCSK9 among patients with stable angina

Jian Zhang, Mingzhi Long, Yichao Yu


Background: Blood lipid management is one of the effective strategies for coronary heart disease, and statins are the first-line lipid-lowering drugs. Low density lipoprotein cholesterol (LDL-C) drop brings about cardioprotective effects. Proprotein convertase subtilisin kexin type 9 (PCSK9) is known to increase LDL-C, thus hazarding LDL-C reduction-induced benefits. To date, how PCSK9 responds to various lipid-lowering strategies has not been fully clarified.
Methods: This study involves patients with stable angina and aims to explore and clarify the short-term impacts of rosuvastatin and ezetimibe, alone or in combination, on circulating PCSK9. A total of 68 patients with stable angina were enrolled and 60 eligible patients were randomly assigned into 3 groups (20 subjects in each). Patients in different groups were treated for a period of 14 days with rosuvastatin 10 mg/d, ezetimibe 10 mg/d, and rosuvastatin 10 mg/d plus ezetimibe 10 mg/d, respectively. Concentrations of blood LDL-C and PCSK9 levels were measured at baseline and at the 14th day after treatment.
Results: Both rosuvastatin and ezetimibe could reduce the LDL-C levels, and rosuvastatin displayed a stronger cholesterol-lowering effect than ezetimibe. Moreover, when combined, they yielded even greater efficacy in lowering LDL-C, as compared with either rosuvastatin or ezetimibe mono-treatment (P<0.05). Rosuvastatin therapy (alone or combined with ezetimibe) caused significant rise in circulating PCSK9. Nevertheless, no significant growth of PCSK9 levels (P=0.558) was observed during ezetimibe treatment. At the 14th day, no difference in PCKS9 levels was observed between the rosuvastatin group and the combination-therapy group (P=0.906).
Conclusions: Rosuvastatin plus ezetimibe therapy is more effective in reducing LDL-C levels as compared with either rosuvastatin or ezetimibe mono-medication. Meanwhile, such combination strategy does not further increase the levels of circulating PCSK9 compared to rosuvastatin mono-intervention, thus maintaining maximal clinical benefits from lipid-lowering.

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