期刊
REVIEWS IN CARDIOVASCULAR MEDICINE
卷 23, 期 11, 页码 -出版社
IMR PRESS
DOI: 10.31083/j.rcm2311375
关键词
hypercholesterolemia; LDL-cholesterol; inclisiran; siRNA; cardiovascular disease
Therapeutic approaches based on gene silencing technologies, such as inclisiran, have shown promise in managing hypercholesterolemia. Inclisiran effectively reduces LDL-C levels and is safe and well-tolerated. A meta-analysis of phase 3 trials demonstrated a significant reduction in LDL-C levels with inclisiran compared to placebo. Although patients receiving inclisiran may experience more reactions at the injection site, overall adverse event incidence is comparable to placebo.
Therapeutic approaches based on gene silencing technologies represent a new opportunity to manage hypercholesterolemia. Inclisiran is a small interfering RNA that targets proprotein convertase subtilisin/kexin type 9 (PCSK9) mRNA. Clinical studies have demonstrated that inclisiran is effective, safe, and well-tolerated in reducing low-density lipoprotein cholesterol (LDL-C) in patients with familial hypercholesterolemia, atherosclerotic cardiovascular disease, and atherosclerotic cardiovascular disease risk equivalents. A meta-analysis of phase 3 trials demonstrated a 51% reduction in LDL-C levels at 18 months as compared with placebo. Adverse event incidence was found to be comparable in individuals treated with inclisiran and those receiving placebo, though the reactions at the site of injection were more common in patients receiving inclisiran as compared with those receiving placebo. The recommended inclisiran dose is 284 mg administered as a subcutaneous injection to be repeated after three months with a subsequent 6-month maintenance regimen. Overall, since the pharmacological efficacy of inclisiran in LDL-C reduction is comparable to that of monoclonal antibodies against PCSK9, the longer effect duration and the favorable safety profile may favor this newer approach for hypercholesterolemia management.
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