Interventional Cardiologist CK Hui Heart Centre / Edmonton Cardiology Consultants Royal Alexandra Hospital & CK Hui Heart Centre Edmonton, Alberta, Canada
Background: Lowering LDL cholesterol reduces cardiovascular events. However, numerous high-risk patients do not achieve guideline informed targets over time. Inclisiran is a novel small interfering RNA molecule that significantly lowers LDL-C by inhibiting the hepatic expression of PCSK-9. The purpose of this study is to describe the potent and sustainable LDL-C lowering effect of inclisiran.
METHODS AND RESULTS: In a clinic partnership, the Royal Alexandra Hospital Foundation, Edmonton Cardiology Consultants, and Novartis Pharmaceuticals initiated a multidisciplinary team to operate a Risk Reduction Clinic. It is run through a large metropolitan cardiology office focusing on secondary prevention and high-risk primary prevention patients. Patients are referred by their Cardiologists. All modifiable risk factors are addressed. Relevant demographic, clinical and outcome characteristics for all consecutive patients are prospectively captured in a purpose-built database.
From January 10, 2023, to April 25, 2025, 1012 patients were assessed in this Clinic, of whom 539 (53.3%) patients did not meet their LDL-C target. After adjustment of lifestyle and other pharmacotherapy, 172 patients met the requirements to initiate inclisiran; of those 150 were treated for secondary prevention and 22 patients for heterozygous familial hyperlipidemia. The mean age of patients started on inclisiran was 62 (10.5) years. 32% of patients were female. 59% of patients were on high dose statin and 41% were on low dose statin. 62% of patients were on ezetimibe. Mean LDL-C prior to inclisiran initiation was 2.90 mmol/L. 157 patients had a repeat lipid profile after their first inclisiran dose. For those, mean LDL-C was 1.26 mmol/L (SD 0.82), representing a 56.6% reduction. This allowed 81% of patients to get to their LDL-C target. The LDL-C lowering effect was preserved up to 21 months (graph1). At the 15 month mark, 56 patients still met the LDL-C target, out of 82 (68%). Non-HDL-C was reduced in a similar fashion, other lipid parameters were not affected by inclisiran (table1). Side effects reported were limited to local injection site reactions including redness, tenderness, and a burning sensation post injection. Out of the 172 patient, 10 discontinued inclisiran for various reasons.
Conclusion: Over a 21-month period inclisiran has proven to be a well-tolerated injectable medication requiring only two injection a year allowing 81% of patients to achieve their respective LDL-C target after one injection and 68% after three injections, with only 6% of patient’s discontinuing treatment.
