Rapid effects of different lipid-lowering drugs on PCSK9 in humans

Background: PCSK9 plays a pivotal role in the metabolism and therefore levels of LDL receptors. Previous studies have reported that statins increased PCSK9 levels in humans. Aims: We prospectively investigated the rapid effects of ezetimibe, Xuezhikang and pitavastatin on PCSK9 levels in humans. Methods: Fifty-four patients with dyslipidema were given ezetimibe 10 mg daily (n = 15), Xuezhikang 0.6 g twice daily (n = 15), ezetimibe 10 mg daily plus Xuezhikang 0.6 g twice daily (n = 15) or pitavastatin 2 mg daily (n = 9) for 3 days. Blood samples were obtained before treatment with lipid-lowering drugs commenced (day 0) and at days 1 and 3 after the treatment, and PCSK9 levels were determined by ELISA. Results: Ezetimibe increased PCSK9 levels by 29% at day 1 and 39% at day 3 (p = 0.006 and 0.048, respectively, compared with day 0); Xuezhikang increased PCSK9 levels by 32% at day 1 and 55% at day 3 (p = 0.016 and 0.010, respectively, compared with day 0); ezetimibe plus Xuezhikang increased PCSK9 levels by 36% at day 1 (p = 0.033 compared with day 0) and 41% (p = 0.074 compared with day 0) at day 3; pitavastatin increased PCSK9 levels by 41% at day 1 and 27% at day 3 (p = 0.002 and 0.037, respectively, compared with day 0). Conclusion: Ezetimibe, Xuezhikang and pitavastatin exhibited rapid effects on PCSK9 levels; however, a combination of ezetimibe and Xuezhikang did not result in a greater increase in PCSK9, compared with monotherapy with either agent.