Effect of early initiation of evolocumab on lipid profiles changes in patients with ACS Undergoing PCI (C-STAR)

Background/Aims Achieving rapid reductions in low-density lipoprotein cholesterol (LDL-C) levels in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) remains challenging. This study investigated the efficacy and safety of early triple combination therapy with evolocumab, a moderate-dose statin and ezetimibe in statin-naïve ACS patients. Method C-STAR (Effect of Early Initiation of Evolocumab on Lipid Profiles Changes in Patients with ACS Undergoing PCI) was an investigator-initiated, single-centre, prospective, randomised trial conducted in South Korea. Patients with ACS and no history of statin use who underwent PCI between December 2022 and January 2025 were enrolled. Patients were randomised to receive an early single-dose injection of evolocumab (140 mg) with statin/ezetimibe or no evolocumab. Both groups received rosuvastatin 5 mg and ezetimibe 10 mg. The primary efficacy endpoint was the difference in LDL-C level at 2 weeks between the two groups and the safety endpoint was cognitive function at 2 weeks using the short version of the Everyday Cognition (ECog) tool with a 23-item questionnaire (scores ranged from 1 to 5, with lower scores representing better function). Results The study included 103 patients (mean age 61.4 ± 11.1 years; 50.5% STEMI), randomised into two groups (52 in the evolocumab group, and 51 in the non-evolocumab group). In the evolocumab group, the median interval between PCI and single-dose injection of evolocumab 140 mg was 1.5 (interquartile range: 0.8-4.6) hours. There was no significant difference in baseline LDL-C level between the two groups (144.1 ± 36.4 in the evolocumab group vs. 140.7 ± 31.7 in the non-evolocumab group). However, LDL-C levels at the 2 weeks were significantly lower in the evolocumab group than in the non-evolocumab group (30.6 ± 15.6 mg/dL vs. 63.7 ± 16.7 mg/dL, p < 0.001). The percentage change in the LDL-C at 2 weeks from baseline was -77.5% ± 12.6% in the evolocumab group and -53.3% ± 12.9% in the non-evolocumab group, with a mean between-group difference of -24.4% (95% CI: -29.6% to -19.4%; p < 0.001) (Fig 1A). The rate of achieving an LDL-C level of <55 mg/dL and LDL >50% reduction at 2 weeks was higher in the evolocumab group than in the non-evolocumab group (84.6% vs. 26.9%, p < 0.001) (Fig1B). For the safety endpoint, there was no significant difference in the ECog cognitive function questionnaire score at 2 weeks (23.96 ± 3.54 points in the evolocumab group vs. 24.65 ± 5.67 points in the non-evolocumab group). Conclusions Early initiation of evolocumab in combination with a moderate-dose statin and ezetimibe demonstrated superior LDL-C reduction and higher target attainment rates without cognitive impairment.