Experience with the New Generation of Lipid-lowering siRNA-based PCSK9 Inhibitor (Inclisiran) in Patients Undergoing LMCA Intervention

Background: Coronary artery diseases are one of the leading risk factors for global death.Reducing the levels of low-density lipoprotein (LDL) cholesterol to the normal value is crucial for its treatment.Although medications such as statins and ezetimibe remain the primary therapeutic options in such cases, more effective treatment choices are warranted for high-risk patients, particularly those with a history of cardiovascular events.The new-generation lipid-lowering siRNA drug PCSK9 inhibitor may offer an advantage in controlling LDL levels in such a patient group, especially when used in combination with other hypolipidemic drugs. Aim:To investigate the effect of PCSK9i in patients with prior left main coronary artery intervention. Study Design: Retrospective cohort study.Methods: This study was conducted in Azerbaijan during 2022-2023 with 279 patients who underwent left main coronary artery (LMCA; angioplasty and bypass) intervention.All patients were initiated on statin-based antilipidemic therapy after the intervention.Over one year, the statin dose was titrated to the maximum levels, and ezetimibe was added to the treatment when needed.At the end of the year, patients who had not yet reached the target LDL levels inclisiran were added to the treatment for those who accepted it.Under inclisiran therapy, the patients were monitored for the next 12 months.After the first dose of inclisiran, the second and third doses were administered at the 3 rd and 9 th months, respectively, and LDL levels were measured at the 6 th and 12 th months.During the treatment period, LDL levels, liver enzymes, and other potential side effects were monitored. Results:In patients who received inclisiran therapy (15), the average LDL level directly before inclisiran treatment was 134.9 mg/dL, and six months after treatment with inclisiran, this value dropped to 64.6 mg/dL.In other words, 6 months after starting inclisiran therapy, an average reduction of 52% in LDL levels was observed compared with the previous value.In patients who continued inclisiran treatment, the LDL level at the 12 th month decreased to even lower values (an average of 43.1 mg/dL) compared with the previous measurement.Additionally, only a few patients reported side effects, which were temporary and not clinically significant. Conclusion:Inclisiran significantly reduces LDL levels in patients with LMCA intervention and helps optimize the treatment strategies for achieving target LDL values.However, the high cost and the lack of patient awareness were the key barriers to its widespread use.Reforms in the healthcare system and expanded treatment coverage are expected to improve the effectiveness of Inclisiran and help prevent future cardiovascular diseases.