{
  "abstract": "Introduction Inclisiran is a novel small interfering RNA (siRNA)-based therapy designed to inhibit the expression of the PCSK9 (Proprotein Convertase Subtilisin/Kexin type 9) gene. By doing so, it enhances the recycling and membrane expression of LDL receptors in hepatocytes, leading to a reduction in LDL cholesterol (LDL-c) levels. Despite its promising mechanism, there is limited real-world data on its safety and effectiveness in achieving LDL-c reduction targets.Objective This study aimed to assess the efficacy of Inclisiran in lowering LDL cholesterol levels and to evaluate its safety profile over a one-year period in patients with hyperlipidaemia.Methodology A total of 77 patients (mean age 66.5 ± 10.2 years, 72.7% male, 27.3% female, 30 Asians, 47 Caucasians) were enrolled and followed from September 2023 to September 2024. Baseline characteristics included medical histories of hypertension, diabetes, chronic kidney disease (CKD), smoking status, and prior acute coronary syndrome (ACS). Lipid profiles were assessed three months after a single dose of Inclisiran to evaluate changes in LDL-c levels. The study compared LDL-c reductions across various treatment regimens, including Inclisiran monotherapy and combinations with low-dose statins, high-dose statins, ezetimibe, or other lipid-lowering drugs. Statistical analyses, including paired t-tests, ANOVA, and independent sample t-tests, were performed using IBM SPSS Statistics version 25 to determine significant differences.Results Of the 77 patients, 71 completed the study, with one death and five lost to follow-up. Inclisiran treatment resulted in a significant mean LDL-c reduction of 53.8% (from 3.4 ± 0.8 mmol/L to 1.57 ± 0.77 mmol/L, p < 0.05). Total cholesterol levels also decreased significantly (from 5.39 ± 1.10 mmol/L to 3.64 ± 1.05 mmol/L, p < 0.05), while changes in HDL cholesterol and triglycerides were mild and not statistically significant.Ethnic differences were observed, with Asians achieving a greater mean LDL-c reduction (61.58%) compared to Caucasians (50.41%, p < 0.05). Subgroup analysis revealed significant variations in LDL-c reduction based on treatment regimens. The greatest reduction was seen in patients receiving Inclisiran combined with statins and ezetimibe (69.03%), followed by Inclisiran with high-dose statins (64.40%) and low-dose statins (52.20%). In contrast, Inclisiran monotherapy achieved a 41.12% reduction, and combinations with other lipid-lowering drugs resulted in a 46.04% reduction. These differences were statistically significant (p < 0.05), highlighting the superior efficacy of combination therapies. %. This difference was statistically significant (p < 0.05), which highlights the superior efficacy of combination therapies involving Inclisiran (figure 1).Abstract 7-008 Figure 1Patients on baseline statin therapy showed a greater mean LDL-c reduction (61.4%) compared to those not on statins (43.77%, p < 0.05). Three patients experienced an increase in LDL-c post-treatment, potentially due to drug resistance. The safety profile of Inclisiran was favourable, with only three patients reporting mild local injection site irritation.Conclusion Inclisiran significantly reduces LDL cholesterol levels, with the greatest efficacy observed when used in combination with statins and ezetimibe. Efficacy varied by ethnicity and was enhanced in patients already on statin therapy. The drug demonstrated a favourable safety profile with minimal adverse effects. These findings emphasize the importance of optimizing lipid-lowering regimens to achieve superior LDL-c reductions in clinical practice.",
  "authors": [
    {
      "affiliations": [
        "University Hospitals Birmingham"
      ],
      "name": "Ayham Al-Shatanawi"
    },
    {
      "affiliations": [
        "Rawalpindi Medical University, Rawalpindi Pakistan"
      ],
      "name": "Uzma Aftab"
    },
    {
      "affiliations": [
        "Barcelo Foundation-University, Argentina,"
      ],
      "name": "Sara Costa"
    },
    {
      "affiliations": [
        "University of science and technology, Jordan"
      ],
      "name": "Ayah Bani Mostafa Jordan"
    },
    {
      "affiliations": [
        "University Hospitals Birmingham"
      ],
      "name": "Anwar Hussain"
    },
    {
      "affiliations": [
        "University Hospitals Birmingham"
      ],
      "name": "Nazish Khan"
    },
    {
      "affiliations": [
        "University Hospitals Birmingham"
      ],
      "name": "Mark Thomas"
    },
    {
      "affiliations": [
        "University Hospitals Birmingham"
      ],
      "name": "Sohail Khan"
    }
  ],
  "title": "7-008 A one-year observational study of inclisiran in a secondary prevention clinic for patients with high atherosclerotic cardiovascular disease risk",
  "uid": "744c8a35-ef42-5d2d-90b3-bc328f3e37e0"
}