Background: Statin alone or nonstatins as add-ons have been introduced to intensive low-density lipoprotein cholesterol (LDL-C) lowering therapy in patients at high cardiovascular disease (CVD) risk. The purpose of this study was to evaluate the effectiveness and safety of different statin-based regimens for patients at high risk.

Methods: Three hundred patients at high CVD risk were randomly assigned to the statin group (Rosuvastatin 20mg/d), statin_EZ group (Rosuvastatin 10mg/d + ezetimibe 10mg/d),  statin_pcsk group (Rosuvastatin 10mg/d + alirocumab 75mg/2weeks) or combine3 group (Rosuvastatin 10mg/d + ezetimibe 10mg/d + alirocumab 75mg/2weeks). The primary outcome measure was cholesterol levels (LDL-C, total cholesterol (TC) triglycerides (TGs), and high-density lipoprotein cholesterol (HDL-C)) after 24 weeks of follow-up. The secondary outcome measures were safety markers and the proportion of patients who achieved the < 70 mg/dL (1.8 mmol/L) LDL-C target. A logistic regression model was performed to explore the factors affecting lipid target achievement.

Results: The TC and LDL-C levels after treatment were significantly different among the four groups (p < 0.05). The levels in both the combine3 group and the statin_pcsk9 group were significantly lower than those in the statin group and the statin_EZ group (p < 0.05), but there was no significant difference between the combine3 group and the statin_pcsk9 group. The incidence of adverse events in the four groups was low. Body mass index (BMI) and hypertensive status were related to target achievement.

Conclusion: The combination of a statin and a PCSK9 inhibitor was safe and more effective for the treatment of high-risk CVD patients, while the addition of ezetimibe was unable to significantly lower lipid levels any further. The rate of achieving the target was higher in patients with hypertension and a low BMI.

Laboratory tests, including tests for lipid levels (LDL-C, total cholesterol (TC) triglycerides (TGs), and high-density lipoprotein cholesterol (HDL-C)), liver and renal function tests, and creatine kinase (CK) tests, were conducted prior to the treatment and at the 12^th week and 24^th week. Information on sex, age, smoking history, hypertension, diabetes history, body mass index (BMI) and other related medical history was collected. The patients were followed up for 24 weeks.