Fast Decline of Low-Density Lipoprotein Cholesterol after a First Dose of Inclisiran: A Case Report

Background: Inclisiran is a novel PCSK9 reducing drug acting via siRNA. Its advantage for adherence is a long action allowing for only twice-a-years’ administration. However, study development programs did not investigate the early slope of lipid decrease, which nevertheless, would be of high interest because a faster lowering of LDL-C could lead to a better outcome for the patient. Therefore, in this case report, a close-meshed analysis of lipid effects after inclisiran administration is reported. Patient information: An 84-year-old male patient was admitted to our hospital because of acute decompensated heart failure. His medical history included coronary artery disease and several cardiovascular risk factors, including hypercholesterolemia. Findings: Due to an intolerance to three different statins the patient was not willing to take any oral lipid lowering therapy, thus he received inclisiran. His baseline LDL-C was 174mg/dL, and he received an initial subcutaneous dose of 284mg of inclisiran; LDL-C dropped to 138mg/dL (-21%) after five days, to 101mg/dL (-42%) after 10 days, 79mg/dL (-55%) after two weeks and 77mg/dL (-56%) after three weeks. The reduction of total cholesterol and apo-lipoprotein B ran approximately parallel to the course of LDL-C. Conclusion: Inclisiran exerts a prompt lipid lowering effect after a first subcutaneous administration; LDL-C as well as total cholesterol and apo-lipoprotein B steadily decrease for two weeks before flattening. This comparably fast LDL-C reduction is one further strength of this new drug. From our data we conclude that, as early as two weeks after administration, the effect of the drug can be assessed.