PCSK9 monoclonal antibodies: An overview

Abstract

PCSK9 monoclonal antibodies are novel lipid-lowering therapy that have been extensively studied in patients with hypercholesterolemia either as monotherapy or as an add-on to other LLTs. PCSK9 monoclonal antibodies have significantly reduced the low-density lipoprotein cholesterol (LDL-C) plasma level resulting in a better LDL-C goal attainment. The commercially available PCSK9 monoclonal antibodies, alirocumab and evolocumab, have demonstrated reductions in major adverse cardiovascular events such as myocardial infarction, stroke, unstable angina, and the need for coronary revascularization but not mortality. PCSK9 monoclonal antibodies have demonstrated a favorable safety profile. The most reported side effects are mild injection site with no causal relationship proven between the inhibition of PCSK9 and neurocognitive or glycemic adverse events. In this overview, the efficacy and safety of PCSK9 monoclonal antibodies in the treatment of primary and familial hypercholesterolemia will be discussed.

Hypercholesterolemia: A literature review on management using tafolecimab – a novel member of PCSK9 monoclonal antibodies

“…Commonly reported side effects include injection site reactions, nasopharyngitis, and upper respiratory tract infections 115 . Furthermore, no causal relationship has been proven between the inhibition of PCSK9 and neurocognitive or glycemic adverse events 116 . In the study by Litong and colleagues, the incidence of adverse events was lower in the Tafolecimab group than in the placebo group (41.5% with Tafolecimab versus 54.1% with placebo).…”

Anti-atherosclerotic therapies: Milestones, challenges, and emerging innovations

“… 45 , 46 In 2015, the US Food and Drug Administration (FDA) approved a new class of lipid-lowering therapies that consisted of humanized monoclonal antibodies (mAb) that inactivate PCSK9, alirocumab, and evolocumab. 47 However, PCSK9 mAb treatment requires frequent injections due to their short half-lives and are very expensive, so they are prescribed for high-risk patients who are intolerant to statins or who have failed to reduce LDL-cholesterol levels despite taking the maximum tolerated dose of a statin and ezetimibe. In December 2021, the FDA approved Leqvio (inclisiran), a small interfering RNA (siRNA) therapy that targets PCSK9 mRNA to reduce its synthesis in the liver and decrease LDL-cholesterol levels by ∼50% after subcutaneous administration every 6 months.…”

Acute thrombotic occlusion involving three coronary arteries. A unique association withCOVID‐19 pneumonia

“…[9][10][11] It was found that thrombosis plays a major role in the morbidity and mortality of the disease. [9][10][11] In addition, multiple reports described an association between COVID-19 and coronary artery thrombosis. [12][13][14][15] However, only few cases described simultaneous two-coronary vessels acute thrombosis.…”

“…In a review of 26 studies including more than 11,000 COVID‐19 patients, the pooled prevalence of acute myocardial injury evident by elevation of cardiac biomarkers (high‐sensitivity troponins and creatine kinase MB) was found to be around 20%, and appeared to be associated with disease severity and prognosis 8 . Several studies and systematic reviews described the relationship between COVID‐19 and the increased risk of thrombosis 9–11 . It was found that thrombosis plays a major role in the morbidity and mortality of the disease 9–11 .…”

“…8 Several studies and systematic reviews described the relationship between COVID-19 and the increased risk of thrombosis. [9][10][11] It was found that thrombosis plays a major role in the morbidity and mortality of the disease. [9][10][11] In addition, multiple reports described an association between COVID-19 and coronary artery thrombosis.…”