Effect of an siRNA Therapeutic Targeting PCSK9 on Atherogenic Lipoproteins

Kausik K. Ray, Robert M. Stoekenbroek, David Kallend, Lawrence A. Leiter, Ulf Landmesser, R. Scott Wright, Peter Wijngaard, John J. P. Kastelein

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92 Citations (Scopus)


RESULTS: The mean age of the 501 participants was 63 years, 65% were male, 69% had atherosclerotic cardiovascular disease, 73% used statins, and mean low-density lipoprotein cholesterol was 128 mg/dL. A single dose of inclisiran reduced apo B, non-HDL-C, and very-low-density lipoprotein cholesterol over 210 days. A second dose of inclisiran provided additional lowering of these lipids. At day 180, non-HDL-C was lowered dose-dependently: by 25% from 148±43 to 110±45 mg/dL in the 200-mg single-dose group and by 46% from 161±58 to 91±58 mg/dL in the 2-dose 300-mg group. For the same dosing regimens, apo B was reduced by 23% from 101±23 to 78±29 mg/dL and by 41% from 106±31 to 65±33 mg/dL ( P<0.001 for all groups versus placebo). In the 300-mg 2-dose group, all individuals experienced apo B and non-HDL-C reductions. There was larger interindividual variation in very-low-density lipoprotein cholesterol, triglycerides, and lipoprotein(a) reductions. In the 300-mg 2-dose group, the percentages of patients achieving guideline-recommended apo B goals for high- and very-high-risk patients at day 180 were 78% and 90%; 68% and 83% of participants achieved non-HDL-C <100 and <130 mg/dL.
Original languageEnglish
Pages (from-to)1304-1316
Issue number13
Publication statusPublished - 2018

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