Efficiency of dyslipidemia therapy using Inclisiran in a series of clinical observations of kidney transplant patients

Relevance. Dyslipidemia is a risk factor for cardiovascular diseases leading to death in the late period after kidney transplantation.

Objective. Evaluation of the efficacy and safety of combination therapy for dyslipidemia with inclisiran in a group of patients with a transplanted kidney.

Material and methods. A single-center observational uncontrolled cohort study of the efficacy and safety of lipid-lowering therapy (LLT) using inclisiran in a group of patients with dyslipidemia after kidney transplantation was conducted. Data on 10 patients are presented: 8 (80%) women, mean age 39.8±10.5 years. At stage I, basic LLT was prescribed, at stage II, inclisiran was added to the treatment on days 1, 90, and 270. Follow-up period at stage I was 102 days, at stage II – 301 days. Efficacy and safety were assessed at 7 control points. Therapy efficacy was assessed by reducing low-density lipoprotein (LDL) levels, achieving blood LDL level ≤1.4 mmol/L, and the duration of maintaining the achieved effect (days). Blood levels of lipoprotein (a) – Lp(a), triglycerides (TG), and high-density lipoprotein (HDL) were also studied. Safety was assessed based on complaints, general examination and injection site data, alanine aminotransferase (ALT), aspartate aminotransferase (AST), glomerular filtration rate (GFR), blood immunosuppressant drug concentrations, daily proteinuria, and renal ultrasound results.

Results. A decrease in LDL levels by an average of >50% was revealed 30 days after each injection in 6 (60%) patients, and from 8.6 to 46% - in 4 (40%). The dynamics of HDL and TG levels were multidirectional. In 3 patients with elevated Lp(a) levels, a decrease in its level by 5.1–7.4% was revealed. At stage I, basic LLT therapy was ineffective. At stage II, LDL levels ≤1.4 mmol/l were achieved by 2 (20%) patients at points 2 and 3, 5 (50%) patients – at point 4, 3 (30%) – at point 5, 1 (10%) patient – at point 6, and 2 (20%) patients at point 7. A total of 7 patients achieved LDL levels ≤1.4 mmol/l with a median of 47 [IQR: 3; 90] (1; 112) days. LDL levels ≤1.8 mmol/l were achieved in 8 patients with a median of 98.5 [IQR: 61; 236.7] (42; 255) days. In 5 (50%) patients, a decrease in GFR by an average of “minus” 13.6±13.9% (-36.4; -0.1%) was detected. In the remaining 5 (50%) patients, the mean GFR value increased by 15.1±17.3% (1.7%; 42.6%). In all 10 patients, the level of daily proteinuria decreased by an average of 50.4±16.9% (25.6%; 76.9%).

Conclusion. The efficacy of the basic LLT (n=8) in reducing the LDL level compared to the baseline was on average 23.5±10.5% (1.9%; 39.6%) [95% CI 8.9–26.3%], the efficacy of the drug inclisiran was 48.9±20.4% (8.6%; 70.9%) [95% CI 34.3–63.5%]. The efficacy of all applied LLT in all patients was on average 59.9±22.5% (8%; 81.1%) [95% CI 43.8–76.0%]. The median of days with the LDL level ≤1.4 mmol/L in 7 patients was 47 [IQR: 3; 90] (1; 112) days, which amounted to a median share of 15.6% [IQR: 1%; 29.9%] (0.3%; 37.2%) of the total follow-up period (301 days). No side effects indicating poor tolerability of the drug were detected during the use of inclisiran.