AIM:To observe the efficacy and safety of combined lipid-lowering strategies in the initial stage of treatment in "very high-risk ASCVD" patients in cardiology outpatient clinics in a real-world prospective cohort study. METHODS: Patients with "very high-risk ASCVD" from January to June 2021 were consecutively enrolled and divided into three groups according to the actual lipid-lowering treatment strategies: Atorvastatin group; Atorvastatin combine with ezetimibe group; Atorvastatin combine with evolocumab group. The primary observation endpoints were the changes in LDL-C, Lp(a), and non-HDL-C after one month of treatment, and the secondary endpoints were the changes in TC, TG, HDL-C, Hs-CRP, and safety indicators. RESULTS: The efficacy of the combined lipid-lowering strategy in the initial stage of treatment was significantly better than that of the Atorvastatin group: LDL-C, Log ［Lp(a)］, non-HDL-C, TC significantly decreased (all P<0.05). Compared with the Atorvastatin combine with Ezetimibe group, LDL-C and Log ［Lp(a)］ decreased significantly in the Atorvastatin combine with Evolocumab group (P<0.05), and TC and TG had decreased insignificantly (P>0.05). When "LDL-C <1.4mmol/L or <1.8 mmol/L" is used as the standard for lipid-lowering compliance, the LDL-C compliance rates of the two groups of combined lipid-lowering treatments are higher than those of the atorvastatin single-drug group. The differences were all statistically significant (all P<0.05); the LDL-C compliance rate of the atorvastatin combined with evolocumab group was higher than that of the atorvastatin combined with ezetimibe group, and the differences were statistically significant (All P<0.05). When the reduction rate of "LDL dropped by more than 50%" alone or in combination were used as the standard, no one in the three groups could reach the standard.The liver aminotransferase levels had no significant changes among the 3 groups after treatment (all P>0.05). Myocardial enzyme isoenzyme (CK-MB) decreased among the 3 groups insignificantly (P>0.05). Compared with the Atorvastatin group, the blood sugar (BS) of the two combined lipid-lowering groups decreased significantly (P<0.05); The BS of the Atorvastatin + ezetimibe group significantly decreased than that of Atorvastatin combine with Evolocumab group (P<0.05). CONCLUSION: The lipid-lowering effect and LDL-C compliance rate of patients with "very high-risk ASCVD" in the cardiology outpatient department after 1 month of combined lipid-lowering treatment were better than those of the atorvastatin monotherapy group.When LDL-C <1.4 mmol/L or <1.8 mmol/L is the lipid-lowering target, the LDL-C compliance rate after 1 month of treatment in the atorvastatin combined with evolocumab group is higher than that of the combined atorvastatin and zetamibu group. When the "LDL drop by more than 50%" is used as the standard for lipid lowering, it is difficult to reach the standard within 1 month. Outpatient "very high-risk ASCVD" patients were treated with initial combined lipid-lowering therapy for 1 month without adverse reactions. The initial combined lipid-lowering strategy can be used for patients with "very high-risk ASCVD" in cardiology outpatient clinics who need to achieve LDL-C values early. Atorvastatin combined with evolocumab strategy can be recommended for those patients who require LDL-C<1.4 mmol/L or <1.8 mmol/L within one month.