Do Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) inhibitors increase Coronary Artery Calcium (CAC) scores?

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Last updated: March 5, 2025View editorial policy

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From the Guidelines

PCSK9 inhibitors do not increase Coronary Artery Calcium (CAC) scores, and by lowering LDL cholesterol levels, they may help slow the progression of atherosclerosis, which contributes to arterial calcification over time. These medications, including evolocumab and alirocumab, work by blocking the PCSK9 protein, allowing more LDL receptors to remain on liver cells, resulting in lower LDL cholesterol levels in the bloodstream 1. Current evidence does not suggest that PCSK9 inhibitors increase coronary artery calcification as measured by calcium scoring. In fact, studies such as the FOURIER trial have demonstrated that evolocumab reduces LDL cholesterol by 59% and significantly reduces the composite outcome of cardiovascular death, MI, stroke, hospitalization for angina, or revascularization 1.

Some key points to consider:

  • The effects of PCSK9 inhibition on ASCVD outcomes were investigated in the FOURIER trial, which enrolled 27,564 individuals with prior ASCVD and an additional high-risk feature who were receiving their maximum tolerated statin therapy 1.
  • The ODYSSEY OUTCOMES trial also demonstrated that alirocumab plus statin therapy resulted in a greater absolute reduction in the incidence of the primary endpoint in people with diabetes 1.
  • It's essential to note that calcium scores naturally tend to increase over time regardless of treatment, and this progression doesn't necessarily indicate worsening cardiovascular risk when occurring in the context of effective lipid-lowering therapy.
  • Patients on PCSK9 inhibitors should continue regular follow-ups with their healthcare provider to monitor overall cardiovascular health beyond just calcium scores.

The evidence from recent studies, such as those published in 2023 1, supports the use of PCSK9 inhibitors in reducing LDL cholesterol levels and improving cardiovascular outcomes, without increasing coronary artery calcification. Therefore, PCSK9 inhibitors can be a valuable treatment option for patients with high cardiovascular risk, and their use should not be limited by concerns about increasing CAC scores.

From the Research

PCSK9 Inhibitors and Coronary Artery Calcium (CAC) Scores

  • There is no direct evidence in the provided studies that PCSK9 inhibitors increase Coronary Artery Calcium (CAC) scores 2, 3, 4, 5, 6.
  • The studies focus on the effectiveness of PCSK9 inhibitors in reducing low-density lipoprotein cholesterol (LDL-C) levels and improving cardiovascular outcomes, but do not mention the specific effect on CAC scores.
  • Some studies discuss the role of PCSK9 in cholesterol homeostasis and its potential as a target for treating hyperlipidemia and atherosclerosis, but do not provide information on CAC scores 3, 4.
  • Other studies review the available data on the effect of PCSK9 inhibitors on cardiovascular outcomes, but do not mention CAC scores specifically 2, 5, 6.

Key Findings

  • PCSK9 inhibitors have been shown to reduce LDL-C levels and improve cardiovascular outcomes 2, 3, 5.
  • The inhibitors have been found to be effective in reducing the risk of cardiovascular events, including myocardial infarction, stroke, and death 2, 3, 5.
  • However, there is no direct evidence on the effect of PCSK9 inhibitors on CAC scores, which is a measure of coronary artery calcium and a marker of atherosclerotic plaque burden.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

PCSK9 inhibitors and cardiovascular outcomes.

Expert opinion on biological therapy, 2020

Research

Targeting PCSK9 to tackle cardiovascular disease.

Pharmacology & therapeutics, 2023

Research

PCSK9: A key factor modulating atherosclerosis.

Journal of atherosclerosis and thrombosis, 2015

Research

PCSK9 inhibitors--past, present and future.

Expert opinion on drug metabolism & toxicology, 2015

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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