(P057) SAFETY AND EFFICACY OF INCLISIRAN IN BOTH PRIMARY AND SECONDARY PREVENTION IN A CONTEMPORARY CANADIAN POPULATION

Background: Lowering LDL cholesterol reduces recurrent cardiovascular events. However, numerous high-risk patients do not achieve guideline secondary prevention targets. Inclisiran is a novel small interfering RNA molecule that lowers LDL by inhibiting the hepatic expression of PCSK-9. This study was designed to describe the initial clinical experience with this novel agent in a contemporary Canadian population of high vascular risk patients.

METHODS AND RESULTS: In a private-public partnership, the Royal Alexandra Hospital Foundation, Edmonton Cardiology Consultants, and Novartis Pharmaceuticals initiated a multidisciplinary team to operate a Risk Reduction Clinic (RRC). It is operated through a large private metropolitan cardiology office focusing on secondary prevention and high-risk primary prevention patients. 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 22, 2024, 623 patients were assessed in the RRC, of whom 307 (49.3%) patients did not meet their LDL target. After adjustment of lifestyle and other pharmacotherapy, 126 patients met the requirements to initiate Inclisiran; of those 110 were treated for secondary prevention and 16 patients for heterozygous familial hyperlipidemia. The mean age of patients started on inclisiran was 62 (12.5) years and 35% of patients were female. There were 61% of patients on high-dose statin, 39% were on low-dose statin, and 63% of patients were on ezetimibe. Mean LDL prior to inclisiran initiation was 2.84 mmol/L (1.00). 95 patients had a repeat lipid profile after their first inclisiran dose. For those mean LDL was 1.29 mmol/L (SD 0.86), representing a 54.6% reduction. This allowed 79% of patients to get to their LDL target. The LDL lowering effect was preserved up to 9 months (Figure 1). Non-HDL was reduced similarly, and other lipid parameters were not affected by inclisiran (Table 1). Side effects reported were limited to local injection site reactions including redness, bruising, and tenderness. Four patients discontinued inclisiran; two patients no longer qualified because they were unable to take statins, one deceased, and one exited the patient support program.

Conclusion: Including inclisiran within an RRC demonstrates promising results in achieving LDL targets among high-risk patients, including those with familial hypercholesterolemia. Our study allowed 79% of patients to achieve their LDL target. This real-world study highlights the efficacy and tolerability of inclisiran in combination with lifestyle adjustments and other pharmacotherapy. Future research should explore long-term effects and potential integration of inclisiran into broader cardiovascular management protocols.