Inclisiran use in clinical practice in patients with dyslipidemia: first results

Inclisiran use in clinical practice in patients with dyslipidemia: first results

E.A. Polyakova¹, S.V. Lapin¹, A.V. Mazing¹, A.V. Lisker¹, M.Yu. Sitnikova², P.A. Fedotov², M.A. Simonenko², V.D. Nazarov¹, Yu.Sh. Khalimov¹ 

¹Pavlov First Saint-Petersburg State Medical University, St. Petersburg

²V.A. Almazov National Medical Research Center, St. Petersburg 

Aim: to analyze the inclisiran use in real clinical practice for primary and secondary prevention of atherosclerotic cardiovascular diseases in patients with dyslipidemia.

Patients and Methods: a retrospective analysis of the treatment data concerning the first 22 patients who received two doses of inclisiran in the period from February 1 to September 20, 2023, was conducted in accordance with the package leaflet. Physical data, history, concomitant lipid-lowering therapy, lipid profile data assessed by the standard methods of biochemical analysis and electrophoresis, lipoprotein (а) (LP(а)) count, and biochemical tests were analyzed initially, after 2 and 4 months from the initiating therapy with inclisiran, as well as the results of genetic testing aimed at excluding familial hypercholesterolemia. Adverse events were also assessed.

Results: after the therapy initiation with inclisiran, a decrease in the mean total cholesterol (TC) was achieved: after 2 months, by 41.0% from 5.1 (4.13; 6.47) to 3.01 (2.77; 4.27) mmol/L, after 4 months by 44.7% from the baseline — to 2.82 (2.46; 3.44) mmol/L (for both measurement points versus the baseline, p<0.001). The low-density lipoprotein cholesterol (LDL-C) also significantly decreased: after 2 months by 47.1%: from 3.08 (2.40; 4.73) to 1.63 (1.10; 2.60) mmol/L, after 4 months by 54.5% from the baseline — to 1.4 (0.87; 1.90) mmol/L (for both measurement points versus the baseline, p<0.001). The mean high-density lipoprotein cholesterol (HDL-C) by the 4^th month from the initiation therapy with inclisiran did not significantly change. The mean TG by the 4^th month of follow-up decreased by 27.9%: from 1.11 (0.97; 1.94) to 0.8 (0.61; 1.43) mmol/L (p<0.001). By the 2nd month of follow-up, a decrease in the mean LP(a) level by 27.8% was also recorded: from 36.0 (16.0; 68.0) to 26.0 (11.0; 46.0) mg/dl (p<0.05). Of the adverse events that were probably related with inclisiran, a topical reaction was registered at the injection site in 1 patient, which resolved spontaneously within 2 hours.

Conclusion: inclisiran use in real clinical practice by the 4^th month from the therapy initiation was accompanied by a significant decrease in serum TC, LDL-C, TG and LP(a) with good tolerability and high efficacy versus the data of ORION research group. The unique mechanism of action, convenient dosing regimen and high clinical efficacy of inclisiran provide wide opportunities for the treatment tactics for patients with dyslipidemia, opening up new possibilities for patients with heterozygous familial hypercholesterolemia, high, very high and extremely-high cardiovascular risk, including heart transplant recipients.

Keywords: inclisiran, lipid-lowering therapy, primary and secondary prevention of cardiovascular diseases, heart transplantation, hemodialysis, lipoprotein (a), heterozygous familial hypercholesterolemia.

For citation: Polyakova E.A., Lapin S.V., Mazing A.V., Lisker A.V., Sitnikova M.Yu., Fedotov P.A., Simonenko M.A., Nazarov V.D., Khalimov Yu.Sh. Inclisiran use in clinical practice in patients with dyslipidemia: first results. RMJ. 2023;9:18–29.