Related Experiment Video

Updated: Nov 8, 2025

A High-Throughput Luciferase Assay to Evaluate Proteolysis of the Single-Turnover Protease PCSK9
08:14

A High-Throughput Luciferase Assay to Evaluate Proteolysis of the Single-Turnover Protease PCSK9

Published on: August 28, 2018

8.3K

A meta-analysis of medications directed against PCSK9 in familial hypercholesterolemia

Julia Brandts1, Kanika I Dharmayat2, Antonio J Vallejo-Vaz2

  • 1Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health, School of Public Health, Imperial College London, London, United Kingdom; Department of Medicine I, University Hospital RWTH Aachen, Aachen, Germany.

Atherosclerosis
|April 26, 2021
PubMed

Insights

PCSK9 inhibitors effectively lower LDL-cholesterol in heterozygous familial hypercholesterolemia (HeFH). This meta-analysis found no significant difference in LDL-C reduction between PCSK9 monoclonal antibodies and small interfering RNA, regardless of genetic variant.

Area of Science:

  • Cardiovascular Medicine
  • Genetics
  • Pharmacology

Background:

  • Heterozygous familial hypercholesterolemia (HeFH) is a genetic disorder characterized by high LDL-cholesterol (LDL-C).
  • PCSK9-targeting medications are a key therapeutic strategy for managing LDL-C in HeFH.
  • Understanding variations in treatment response based on therapeutic approach and genetic factors is crucial.

Purpose of the Study:

  • To evaluate whether LDL-cholesterol reduction varies among different PCSK9-targeting therapies.
  • To determine if the underlying genetic variant influences the efficacy of PCSK9 inhibition in HeFH patients.

Main Methods:

  • A random-effects meta-analysis of randomized clinical trials involving PCSK9 inhibitors (alirocumab, evolocumab, inclisiran) in clinically diagnosed HeFH patients.
  • Analysis was restricted to patients with available genotypic data.
  • Trials were selected based on sufficient duration for stable treatment effect (~12 weeks for mAbs, ~1 year for siRNA).
  • Meta-regression was used to compare LDL-C reduction between drug classes and across genotypes.

Main Results:

  • Eight trials including 1887 genotyped patients met the inclusion criteria.
  • In monogenic HeFH cases, LDL-C reduction was 46.12% for siRNA and 50.4% for mAbs, with no significant heterogeneity between treatments.
  • LDL-C reductions were consistent across various genetic variants, including LDL-receptor and Apolipoprotein B variants.

Conclusions:

  • PCSK9-targeting medications demonstrate consistent LDL-cholesterol lowering effects in HeFH patients.
  • The efficacy of these therapies does not significantly differ between drug classes (mAbs vs. siRNA).
  • Genetic variants do not appear to influence the LDL-C-lowering efficacy of PCSK9 inhibitors in this population.
Abstract

Keywords:
Familial hypercholesterolemiaGenotypeLDL-CholesterolMeta-analysisPCSK9 lowering medication

More Related Videos

LDL Cholesterol Uptake Assay Using Live Cell Imaging Analysis with Cell Health Monitoring08:45

LDL Cholesterol Uptake Assay Using Live Cell Imaging Analysis with Cell Health Monitoring

Published on: November 17, 2018

13.7K
A Familial Hypercholesterolemia Human Liver Chimeric Mouse Model Using Induced Pluripotent Stem Cell-derived Hepatocytes10:56

A Familial Hypercholesterolemia Human Liver Chimeric Mouse Model Using Induced Pluripotent Stem Cell-derived Hepatocytes

Published on: September 15, 2018

8.3K

Related Concept Videos

Lipid-Lowering Drugs: Statins and Miscellaneous Agents01:20

Lipid-Lowering Drugs: Statins and Miscellaneous Agents

Hyperlipidemia, a medical condition often referred to as high cholesterol, is characterized by abnormally elevated levels of lipids in the bloodstream. When present in excess, these lipids, specifically cholesterol and triglycerides, can lead to serious health complications, often involving cardiovascular diseases. Illnesses like atherosclerosis, heart attacks, and pancreatitis have all been linked to untreated hyperlipidemia. This means controlling and regulating cholesterol and triglyceride...
1.1K
Atherosclerosis III: Management01:26

Atherosclerosis III: Management

Management of atherosclerosis involves an integrated strategy encompassing pharmacological treatment, surgical interventions, lifestyle changes, and nutrition therapy to address the multifactorial nature of the disease.Pharmacological TherapyA cornerstone of atherosclerosis management is the use of pharmacological agents. Statins, such as atorvastatin, are pivotal in inhibiting HMG-CoA reductase, an enzyme that catalyzes an initial step in cholesterol synthesis in the liver. This reduction in...
91
Coronary Artery Disease IV: Preventive Measures01:26

Coronary Artery Disease IV: Preventive Measures

Effective preventive measures for coronary artery disease (CAD) focus on controlling modifiable risk factors, including cholesterol abnormalities and lifestyle changes.Cholesterol ManagementFirst, the Mediterranean diet and the American Heart Association advocate for maintaining low-density lipoprotein (LDL) cholesterol levels below 100 mg/dL, with a more stringent recommendation of below 70 mg/dL for individuals at high risk. LDL cholesterol, often termed "bad cholesterol," can lead to the...
441
Coronary Artery Disease V: Interprofessional Care01:27

Coronary Artery Disease V: Interprofessional Care

Interprofessional care for coronary artery disease includes pharmacological therapy and revascularization procedures.Pharmacological therapy for Coronary Artery Disease (CAD) aims to manage symptoms, prevent complications, and improve patient outcomes through various classes of medications:Antiplatelet Agents:Aspirin and Clopidogrel: These medications inhibit platelet aggregation, preventing blood clots, which is crucial for avoiding heart attacks and strokes. Doctors often prescribe these...
93
Antianginal Drugs: Calcium Channel Blockers and Ranolazine01:25

Antianginal Drugs: Calcium Channel Blockers and Ranolazine

Angina pectoris, a primary symptom of ischemic heart disease, requires careful pharmacological interventions. In this context, calcium channel blockers (CCBs) and ranolazine have emerged as crucial pharmacotherapeutic agents, providing deep insights into the complexities of angina management.
CCBs, a diverse class that includes dihydropyridines (nifedipine) and diphenylalkylamines (verapamil and diltiazem), exert their effect by blocking calcium channels in cardiac and smooth muscle cells. This...
883
Peripheral Artery Disease III: Interprofessional Care01:27

Peripheral Artery Disease III: Interprofessional Care

Peripheral Artery Disease (PAD) is characterized by narrowed arteries that diminish blood flow to the extremities. Effective management of PAD requires an interprofessional approach involving various healthcare professionals. The critical aspects of interprofessional care for PAD patients focus on risk factor modification, drug therapy, exercise therapy, nutrition therapy, critical limb ischemia care, and interventional radiology and surgical procedures.The primary treatment goal for PAD...
95