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

Abstract

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 lipidlowering 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 14 th 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 14 th 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.

The efficacy and safety of sodium tanshinone ⅡA sulfonate injection in the treatment of unstable angina pectoris: A systematic review and meta-analysis

“…The Cochrane manual was used to assess the bias of the included literature. A total of 37 [ 9 – 45 ] articles were included, where 2 studies [ 17 , 27 ] used a random number table method, 1 study [ 28 ] used a computer-generated program randomization method, 1 study [ 25 ] mentioned random grouping according to the order of patient visits, 3 studies [ 13 , 36 , 39 ] mentioned random grouping according to the order of admission, and the remaining 30 studies all mentioned random grouping but failed to give specific description to the randomization methods. Besides, 7 studies [ 13 , 17 , 25 , 27 , 28 , 36 , 39 ] identified allocation considerations as high risk, 2 studies [ 10 , 45 ] mentioned the use of single blinding, and the specific assessment information of bias risk included in various studies was shown in Fig 2 .…”

“…9studies [ 19 , 20 , 24 , 25 , 28 , 34 , 41 – 43 ] reported CRP with high heterogeneity ( P< 0.00001, I 2 = 89%), and the random effects model was used for meta-analysis. The results showed that the difference was statistically significant(SMD = -1.39, 95%CI [-1.91, -0.86], P< 0.00001), indicating that the treatment group received better efficacy than the control group in improving the CRP Fig 9 .…”

Changes in circulating pro-protein convertase subtilisin/kexin type 9 levels – experimental and clinical approaches with lipid-lowering agents

“…The largest LDL-C reduction was associated with the largest rise in plasma PCSK9 concentrations, an effect consistent across genders. 69 In a series of 27 hypercholesterolaemic subjects, administration of rosuvastatin for three months resulted in a positive correlation between PCSK9 plasma levels and LDL-C reduction, with a 27% rise of PCSK9 with a dose increase from 5 to 40 mg. 70 In homozygous familial hypercholesterolaemic (HoFH) patients, LDL-C levels were reduced by 16.5% and in heterozygous familial hypercholesterolaemic (HeFH) patients levels were reduced by 48.5%. Conversely, PCSK9 levels increased by 17% in HoFH patients and by 27% in HeFH patients.…”

“…In a clinical trial with 60 patients with stable angina, 14-day therapy with rosuvastatin (10 mg) led to a 19% rise in circulating PCSK9 levels (together with a 60% reduction of LDL-C). 69 In a sub-analysis of the Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) study, one-year treatment with rosuvastatin (20 mg) increased PCSK9 by 35% in women and 28% in men vs a similar fall of LDL-C in the two genders (–55% for women and –53% for men). The largest LDL-C reduction was associated with the largest rise in plasma PCSK9 concentrations, an effect consistent across genders.…”

“…71 Finally, the statin-driven stimulatory effect on PCSK9 levels remained consistent when rosuvastatin was administered in combination with ezetimibe. 69…”