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Background Inclisiran is a first-in-class small interfering RNA therapy that targets hepatic PCSK9 synthesis, resulting in sustained reductions in low-density lipoprotein cholesterol (LDL-c). While randomised trials have demonstrated its efficacy, evidence from real-world clinical practice particularly across diverse ethnic groups and varying background lipid-lowering regimens, remains limited. This study assessed the real-world effectiveness and safety of inclisiran in patients with established ischaemic heart disease (IHD).Methods A dedicated inclisiran clinic for secondary prevention was established at Queen Elizabeth Hospital in September 2023. This 2-year observational study included 105 patients with established ischaemic heart disease (IHD), of whom 101 completed follow-ups (one lost to follow-up). The mean age was 66.56 ± 10.9 years, and 72.4% were male. Ethnic distribution comprised 38.1% Asian and 61.9% Caucasian patients. Baseline statin therapy was present in 57.1% of patients. Clinical presentations included stable angina (75.2%), non-ST-elevation myocardial infarction (13.3%), ST-elevation myocardial infarction (8.6%), and unstable angina (2.9%). Changes in lipid parameters following inclisiran therapy were analysed using paired t-tests, analysis of variance (ANOVA), and independent t-tests, as appropriate.Results Mean LDL-c reduced significantly from 3.48 ± 0.91 mmol/L to 1.63 ± 0.82 mmol/L, representing a 51.34% reduction (p < 0.05). 57 patients (56.43%) achieved a 50% reduction in LDL-c , and 44 patients (43.56%) attained LDL-c <1.4 mmol/L. Combination therapy of inclisiran with high-dose statins or statin plus ezetimibe produced the greatest LDL-c reductions (63.96% and 63.14%, respectively) followed by 49.47% in low dose statin, 49.82% in other lipid lowering drugs and 42.46% LDL-c reduction in inclisiran alone group (p < 0.05 across groups). Baseline statin use was associated with greater LDL-c reduction than no statin therapy (59.97% vs 45.29%, p<0.001). LDL-c reduction was greater in Asians compared with Caucasians (60.11% vs 50.18%, p= 0.021), with no significant sex-based or age-related differences. Mean total cholesterol decreased from 5.5 ± 1.1 mmol/L to 3.5 ± 1.09 mmol/L (33.5% reduction, p < 0.05), with greater reductions observed in statin users and Asian patients (p<0.05). Eight patients experienced MACE (STEMI (4), NSTEMI (3) and (1) patient had stroke). Three patients developed mild injection-site skin rash.Conclusions Inclisiran produced substantial and clinically meaningful reductions in LDL-c and total cholesterol in a real-world IHD population. Lipid-lowering efficacy was enhanced by background statin therapy and differed significantly by ethnicity. Inclisiran was generally well tolerated, supporting its role in contemporary lipid management.