The Food and Drug Administration has approved inclisiran (Leqvio) as adjunct therapy, along with diet and statin therapy, to treat adults with heterozygous familial hypercholesterolemia (an inherited condition that alters how cholesterol is cleared from the blood, producing severely elevated low-density lipoprotein [LDL] cholesterol levels) or clinical atherosclerotic cardiovascular disease (including acute coronary syndromes, peripheral arterial disease, heart attack, and stroke). The drug is approved for people who have been prescribed statins at maximally tolerated doses but still have elevated LDL cholesterol. It is administered subcutaneously.

Inclisiran is a small interfering ribonucleic acid (RNA) that inhibits a type of messenger RNA (mRNA) called proprotein convertase subtilisin kexin type 9 (PCSK9). The drug targets liver cells, where it directs the catalytic breakdown of mRNA for PCSK9. This increases LDL cholesterol receptor recycling and expression on the hepatocyte cell surface, increasing LDL cholesterol uptake and lowering its circulating levels.

Inclisiran's effectiveness was determined in three randomized, double-blind, placebo-controlled trials that enrolled 3,457 individuals with either heterozygous familial hypercholesterolemia or atherosclerotic cardiovascular disease. Despite receiving the maximum tolerated statin dose, these individuals still required additional LDL cholesterol lowering. Participants were followed for 510 days. The first two trials included 1,561 and 1,414 adults, respectively, with atherosclerotic cardiovascular disease. At day 510, LDL cholesterol levels had decreased by 46% to 51% in patients receiving inclisiran but increased by 1% to 4% in those receiving placebo. In the third trial, which included 482 adults with heterozygous familial hypercholesterolemia, LDL cholesterol levels decreased by 40% in those receiving inclisiran but increased by 8% in those receiving placebo. Total cholesterol, apolipoprotein B, and non-high-density lipoprotein cholesterol were also decreased in patients taking inclisiran. The studies have not determined the drug's effect on morbidity or mortality.

Common adverse effects of inclisiran treatment are injection site reactions, arthralgia, urinary tract infection, diarrhea, bronchitis, pain in the extremities, and dyspnea.

Nurses should teach patients that inclisiran is administered subcutaneously by a health care provider and that they will need to return for regular injections. After the first dose of inclisiran, a second dose is given three months later, and then every six months. The nurse should inject inclisiran subcutaneously into the abdomen, upper arm, or thigh, avoiding skin that has active skin disease or injury (such as sunburns, skin rashes, inflammation, or infections). Women prescribed inclisiran should be advised that there is a risk to a developing fetus if pregnancy occurs and that they should use birth control while receiving the drug. If a woman becomes pregnant during treatment, she should discuss with her provider whether the drug should be discontinued. For most patients, treating atherosclerosis during pregnancy is not necessary, as a disruption in chronic therapy for several months is not likely to cause significant long-term complications.

For complete prescribing information for inclisiran, go to http://www.accessdata.fda.gov/drugsatfda_docs/label/2021/214012lbl.pdf.