Abstract Background/Introduction Inclisiran, a small-interfering RNA that reduces hepatic PCSK9 synthesis, provides sustained low-density lipoprotein cholesterol (LDL-C) lowering in clinical trials. Real-world data in high-risk patients receiving intensive lipid-lowering therapy remain limited. Purpose To evaluate the effectiveness and LDL-C goal attainment of inclisiran in routine clinical practice among patients with established atherosclerotic cardiovascular disease treated with maximally tolerated lipid-lowering therapy. Methods A retrospective observational analysis was conducted including patients who initiated inclisiran between 2024 and 2025. Eligible patients had received at least two doses and had available LDL-C measurements both before and after treatment initiation. Lipid profiles were assessed at three time points: prior to starting inclisiran, at 1 month, and at 6 months. Clinical characteristics, concomitant lipid-lowering therapy, changes in lipid parameters and attainment of guideline-recommended LDL-C targets were evaluated. Results Thirteen patients were included (mean age 64 years; 7.7% women). Most received high-intensity statins (92.3%) and ezetimibe (84.6%), while bempedoic acid and icosapent ethyl were used in 30.8% and 15.4%, respectively. No patient had prior exposure to PCSK9 inhibitors. Baseline mean LDL-C was 131 mg/dL. At 1 month, LDL-C decreased to 47 mg/dL (65.9% reduction). At 6 months, LDL-C levels remained clearly below baseline, with a mean value of 63 mg/dL. Total cholesterol decreased by 40.3%, triglycerides by 31.2%, and high-density lipoprotein cholesterol increased by 18.5%. Lipoprotein(a) showed an 87.5% reduction. At last follow-up, 92.3% of patients achieved guideline-recommended LDL-C targets, including 53.8% with ≤40 mg/dL and 38.5% between 40 and 55 mg/dL. Only one adverse event was reported: mild injection-site erythema in a single patient. Conclusions In routine clinical practice, inclisiran produced a rapid and sustained improvement in lipid parameters in high-risk patients already receiving intensive lipid-lowering therapy. The high rate of LDL-C goal attainment supports its usefulness as an effective therapeutic option in the management of persistent hypercholesterolaemia.For image description, please refer to the figure legend and surrounding text. For image description, please refer to the figure legend and surrounding text.
Ochoa et al. (Mon,) studied this question.