Methods for reducing the risk of major adverse cardiovascular events in primary prevention subjects

A method of reducing the risk of a major adverse cardiovascular event (MACE) in a subject that has not experienced a major atherosclerotic cardiovascular disease (ASCVD) event,

• wherein the MACE is cardiovascular death, non-fatal myocardial infarction (MI), non-fatal ischemic stroke, or urgent coronary revascularization,
• wherein the method comprises administering an interfering ribonucleic acid (RNAi) agent to the subject, wherein the RNAi agent comprises:
• an antisense strand comprising the nucleotide sequence 5′-asCfsaAfAfAfgCfaAfaAfcAfgGfuCfuagsasa-3′ (SEQ ID NO:
• 3), and
• a sense strand comprising the nucleotide sequence 5′-csusagacCfuGfudTuugcuuuugu-3′ (SEQ ID NO:
• 4),
• wherein a, g, c, and u are 2′-O-methyl (2′-OMe) modified A, G, C, and U nucleotides, respectively;
• Af, Gf, Cf, and Uf are 2′-fluoro A, G, C, and U modified nucleotides, respectively;
• dT is a deoxy-thymine nucleotide and s is a phosphorothioate linkage;
• and
• wherein the sense strand is conjugated to at least one ligand.