Features of the management of patients during changing the drugs that affect proprotein convertase subtilisin/kexin type 9 (PCSK9)

It is of interest to study a possibility of switching a patient from one class of lipid-lowering drugs, inhibitors of proprotein convertase subtilisin/kexin type 9 (iPCSK9), to another (inclisiran), when the patient has already reached the target level of low-density lipoprotein cholesterol (LDL-C). From a pharmacological point of view, iPCSK9 and small interfering RNA (siRNA) drugs are completely different classes of drugs, although they affect the same target reducing the degradation of low-density lipoprotein (LDL) receptors. Alirocumab and evolocumab directly block circulating PCSK9 in the blood, which leads to an immediate decrease in the blood concentration of LDL-C clinically manifested already on the 1st day after injection. However, inclisiran has a different mechanism of action; it binds to PCSK9 matrix RNA, and shows a clinical effect of reduced the blood level of LDL-C later. In this article, we described several clinical cases of such switches and analyzed the risks for the patient associated with these situations. When changing an iPCSK9 targeted drug in clinical practice, we observed a change in the blood lipid composition, which affected the achievement of the LDL-C goal by the patient. Alirocumab demonstrated the greatest reduction in LDL-C (-56.5% compared to baseline in the first clinical case and -53% in the second), while the inclisiran treatment resulted in 31.4% and 36.2% decreases in LDL-C from baseline, respectively. These cases support a practical approach to changes in therapy; there is no need to change the PCSK9-targeted drug if the patient has achieved the LDL-C goal. However, if a change in therapy is necessary for a number of independent reasons, it is important to monitor blood levels of LDL-C on a regular basis due to the different lipid-lowering efficacy of the drugs. These cases illustrate the importance of a balanced approach to changes in the therapy for dyslipidemia when the patient has achieved the goal and is tolerating the treatment well.

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