Based on carotid artery RI values measured at baseline, all patients were divided into three subgroups: 0.95, 0.95-1.05, and 1.05. In patients with RI 0.95, RI in the Tongxinluo capsule group increased relative to baseline only at 24 months (p = 0.001, p representing interaction = 0.008) ≤ RI ≤ 1.05, and there was no difference in changes in RI over time between the two groups (p = 0.125, p for interaction = 0.210) 1.05, RI was reduced at 12 and 24 months in both groups compared to baseline values, and the mean change in Tongxinluo capsule LS from baseline to 24 months was greater than in the placebo group (p 0.001, p representing interaction 0.001) (Table 2).

Biochemical measurement

Mean LS changes in LDL-C, TC and TG from baseline to 24 months increased in the placebo group and decreased in the Tongxinluo capsule group, with significant differences between the two groups (p = 0.029, p 0.001 and p = opposite changes in serum HDL-C levels between the Tongxinluo capsule and placebo groups, with statistically significant differences between the groups (P = 0.003). However, the interaction P-values of serum LDL-C, TC, and TG levels were all 0.05, indicating that there was no evidence of differences in blood lipids over time between the two groups. In addition, the mean LS change in serum hs-CRP levels from baseline to 24 months did not differ significantly between the two groups (P = 0.127).

Drug-related adverse events

There was no difference in reported adverse reactions between the Tongxinluo capsule and placebo groups. Adverse events considered to be treatment-related occurred in 55/604 patients (9.1%) and 45/605 patients (7.4%) in the Tongxinluo capsule and placebo groups, respectively (P = 0.29), with upper abdominal discomfort and headache being the most common complaints. Compliance analysis based on capsule counts showed that patients in the Tongxinluo capsule and placebo groups were 98.2% and 99.8% compliant with taking the study drug, respectively. 2.2% (13/604) and 3.8% (23/605) of patients in the Tongxinluo capsule and placebo groups were discontinued due to adverse events (see supplemental Appendix IX: Table S2).