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A High-Throughput Luciferase Assay to Evaluate Proteolysis of the Single-Turnover Protease PCSK9
Published on: August 28, 2018
A Comprehensive Review of PCSK9 Inhibitors
Caroline Coppinger1,2, Mohammad Reza Movahed2,3, Veronica Azemawah1,2
18040Pima Community College, Tucson, AZ, USA.
Insights
Newer therapies like PCSK9 inhibitors offer significant reductions in low-density lipoprotein cholesterol (LDL-C) for high-risk patients. These treatments provide effective cardiovascular disease management for those with statin intolerance or suboptimal LDL-C goals.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Cardiovascular disease (CVD) is a leading global cause of mortality.
- Elevated serum low-density lipoprotein cholesterol (LDL-C) is a primary CVD risk factor.
- Statins effectively lower LDL-C but are insufficient for some patients, including those with familial hypercholesterolemia or statin intolerance.
Purpose of the Study:
- To evaluate the role of PCSK9 inhibitors in managing high-risk cardiovascular disease patients.
- To assess the efficacy and safety of PCSK9 inhibitors as an adjunct to statin therapy.
- To highlight treatment options for patients with familial hypercholesterolemia or statin intolerance.
Main Methods:
- Review of clinical trial data on PCSK9 inhibitors and ezetimibe.
- Analysis of LDL-C reduction percentages and major adverse cardiovascular events (MACE).
- Comparison of side effect profiles between statins and PCSK9 inhibitors.
Main Results:
- PCSK9 inhibitors achieve substantial LDL-C reductions (54%-74%) when added to statins.
- Ezetimibe provides a 15%-20% LDL-C reduction when combined with statins.
- PCSK9 inhibitors demonstrate significant MACE reduction in high-risk patients and have a favorable safety profile with rare myopathy.
Conclusions:
- PCSK9 inhibitors represent a significant advancement in managing high-risk cardiovascular disease, especially for statin-intolerant patients or those not at LDL-C goals.
- These agents offer profound LDL-C lowering and clinical benefits, translating to reduced MACE.
- The favorable safety profile of PCSK9 inhibitors, particularly the low incidence of myopathy, enhances their therapeutic value.
Abstract:
Cardiovascular disease (CVD) is the leading cause of death in the United States and worldwide. A major risk factor for this condition is increased serum low-density lipoprotein cholesterol (LDL-C) levels for which statins have been successful in reducing serum LDL-C to healthy concentrations. However, patients who are statin intolerant or those who do not achieve their treatment goals while on high-intensity statin therapy, such as those with familial hypercholesterolemia, remain at risk. With the discovery of PCSK9 inhibitors, the ability to provide more aggressive treatment for patients with homozygous and heterozygous familial hypercholesterolemia has increased. Ezetimibe reduces LDL-C by 15%-20% when combined with statin.2,3 Protein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been found to achieve profound reductions in LDL-C (54%-74%) when added to statins. They have shown dramatic effects at lowering major adverse cardiovascular events (MACE) in high-risk patients4 with LDL-C levels ≥70 mg/dL and can be used in populations that are statin intolerant or not at goal levels with maximally tolerated statin therapy. PCSK9 inhibitors also produce minimal side effects. Myopathy, a common side effect for patients on statins, has been rare in patients on PCSK9 inhibitors. Randomized trials have shown that reduction in LDL-C has translated to clinical benefits even in patients who have not achieved their LDL-C target.
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