Efficacy and safety of inclisiran, evolocumab and alirocumab in patients with high, very high and extreme cardiovascular risk

Aim. To compare efficacy and safety of inclisiran, evolocumab and alirocumab in patients with high, very high and extreme cardiovascular risk (according to data from the Federal Research Center for Cardiology and Microbiology, Novosibirsk).
Material and methods. This prospective two-year observational comparative included 53 patients (43 men and 10 women) with an average age of 61,2±4,7 years. They were treated with alirocumab at a dose of 75 mg (n=9) and 150 mg (n=25), evolocumab 140 mg (n=10), and inclisiran (n=9). Two patients were diagnosed with definite familial hypercholesterolemia according to DLCN criteria, while five patients had a myocardial infarction. Lipid profile, transaminase, creatinine, and glucose levels were assessed after 3, 6, 12, and 24 months. The primary efficacy endpoint was achievement of target low-density lipoprotein (LDL) values. The secondary efficacy endpoint was recurrent cardiovascular events (myocardial infarction, stroke, urgent coronary and non-coronary artery revascularization, critical ischemia and lower extremity amputation). New cases of diabetes and atrial fibrillation were also monitored. Safety was assessed based on clinical data and laboratory parameters, such as transaminase, total bilirubin, creatinine and blood glucose levels. The follow-up period ranged from 6 months to 2 years.
Results. Target LDL cholesterol levels for extreme cardiovascular risk were achieved in 21 of 32 patients, and for very high and high risk levels — in 16 of 21 patients. The average LDL level decreased from 3,71 to 1,47 mmol/L during the period of lipid-lowering therapy, while no differences were found between the treatment subgroups. During the two-year follow-up, no endpoints were observed in the study patients. High compliance and good tolerability of all types of treatment with no adverse reactions, including local ones, were noted. None of the patients discontinued therapy.
Conclusion. This single-center study showed that therapy with a PCSK9 inhibitor and inclisiran was well tolerated, and LDL-C reduction was similar to that observed in randomized, placebo-controlled trials.

1. Visseren FLJ, Mach F, Smulders YM, et al. ESC Scientific Document Group. 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice: Developed by the Task Force for cardiovascular disease prevention in clinical practice with representatives of the European Society of Cardiology and 12 medical societies With the special contribution of the European Association of Preventive Cardiology (EAPC). European Heart Journal. 2021;42(34):3227-337. doi: 10.1093/eurheartj/ehab484.

2. Lamb YN. Inclisiran: First Approval. Drugs. 2021;81(3):389-95. doi: 10.1007/s40265-021-01473-6. Erratum in: Drugs. 2021;81(9):1129.

3. Karpov Yu A. The Role of PCSK9 Inhibitors in the Improvement of Outcomes in Patients after Acute Coronary Syndrome: Results of ODYSSEY OUTCOMES Trial. Rational Pharmacotherapy in Cardiology. 2018;14(6):922-34. (In Russ.) doi: 10.20996/1819-6446-2018-14-6-922-934.

4. O'Donoghue ML, Giugliano RP, Wiviott SD, et al. Long-Term Evolocumab in Patients With Established Atherosclerotic Cardiovascular Disease. Circulation. 2022;146(15):1109-19. doi: 10.1161/CIRCULATIONAHA.122.061620.

5. Ray KK, Wright RS. Plain language summary of results from ORION-10 and ORION-11: two studies to learn how well inclisiran works in people with high cholesterol. Future Cardiol. 2023;19(4):175-84. doi: 10.2217/fca-2022-0133.

6. Drapkina OM, Kontsevaya AV, Kalinina AM, et al. Prevention of chronic non-communicable diseases in the Russian Federation. National guidelines. Cardiovascular Therapy and Prevention. 2022;21(4):3235. (In Russ.) doi: 10.15829/1728-8800-2022-3235.

7. Rossini E, Biscetti F, Rando MM, et al. Statins in High Cardiovascular Risk Patients: Do Comorbidities and Characteristics Matter? Int J Mol Sci. 2022;23(16):9326. doi: 10.3390/ijms23169326.

8. Yezhov MV, Kukharchuk VV, Sergienko IV, et al. Disorders of lipid metabolism. Clinical guidelines 2023. Russian Journal of Cardiology. 2023;28(5):5471. (In Russ.) doi: 10.15829/1560-4071-2023-5471. EDN YVZOWJ.

9. O'Donoghue ML, Fazio S, Giugliano RP, et al. Lipoprotein(a), PCSK9 Inhibition, and Cardiovascular Risk. Circulation. 2019;139(12):1483-92. doi:10.1161/CIRCULATIONAHA.118.037184.

10. Nissen SE, Nicholls SJ. Results of the GLAGOV trial. Cleve Clin J Med. 2017;84 (12 Suppl 4):e1-e5. doi: 10.3949/ccjm.84.s4.01. PMID: 29281604.

11. Ray KK, Raal FJ, Kallend DG, et al. ORION Phase III investigators. Inclisiran and cardiovascular events: a patient-level analysis of phase III trials. Eur Heart J. 2023;44(2): 129-38. doi: 10.1093/eurheartj/ehac594.

12. Pérez de Isla L, Díaz-Díaz JL, Romero MJ, et al. SAFEHEART Investigators. Characteristics of Coronary Atherosclerosis Related to Plaque Burden Regression During Treatment With Alirocumab: The ARCHITECT Study. Circ Cardiovasc Imaging. 2024;17(1):e016206. doi: 10.1161/CIRCIMAGING.123.016206.

13. Wu F, Juonala M, Jacobs DR Jr, et al. Childhood Non-HDL Cholesterol and LDL Cholesterol and Adult Atherosclerotic Cardiovascular Events. Circulation. 2024;149(3):217-26. doi: 10.1161/CIRCULATIONAHA.123.064296.