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.