Heart Imaging Shows Real-Time Changes in Plaque

Cardiologists are now able to capture images of the inside of heart arteries, allowing them to monitor how plaque reacts to potent cholesterol medications in real-time.

Research indicates that PCSK9 inhibitors, which block a protein that controls cholesterol, can shrink and stabilize plaque within about a year of starting treatment.

This imaging stems from international studies that scanned the same artery segments in hundreds of patients both before and after therapy. Teams from leading hospitals across Europe and North America collaborated to analyze how these medications impact arteries deep within the body.

Significant Developments in Artery Imaging

For quite some time, doctors have been monitoring coronary atherosclerosis, a gradual buildup of fatty plaque in heart arteries, using angiograms that only show the vessel channel but don’t reveal the hidden materials within the vessel walls.

These images indicated where arteries were narrowed but provided little insight into the composition inside the walls. A recent review compiled various studies utilizing invasive imaging techniques to observe how PCSK9 treatment alters coronary plaque in living patients.

The research was spearheaded by Massimiliano Ruscica, PharmD, PhD, affiliated with the University of Milan, whose work focuses on understanding PCSK9, atherosclerosis, and lipid-lowering treatments.

The Connection Between Cholesterol and Plaque

For many years, the focus of treatment has been on reducing low-density lipoprotein (LDL) cholesterol, a blood fat responsible for boosting plaque growth, while also counting heart attacks and strokes. Statins have effectively reduced these events, but many patients continued to face issues even when their lab results appeared normal.

PCSK9 inhibitors keep more LDL receptors active in the liver, helping the body clear excess LDL particles from the bloodstream. Consequently, they can lower LDL cholesterol levels significantly more than what most people achieve with statins alone.

The FOURIER outcomes trial demonstrated that adding evolocumab to statin therapy significantly reduced LDL to about 30 mg/dL, concurrently lowering major cardiovascular events in high-risk patients. This raised an important question about whether the improvements stemmed solely from shifting blood values or also from actual changes in plaque inside the artery walls.

To address this, researchers needed to examine the plaques directly instead of relying on cholesterol level estimates. New invasive imaging tools have enabled observation of plaque dynamics over time in the same artery segments.

Innovative Intravascular Imaging Techniques

Emerging tools like intravascular ultrasound, which employs a catheter to produce internal images of artery walls, now allow cardiologists to gauge plaque volume rather than just the openness of the channel. The same catheter can be used again months later, enabling before-and-after comparisons of the identical section of the vessel.

Using light-based optical coherence tomography, a high-resolution technique that employs reflected light, medical professionals can view the thin fibrous layer covering a plaque’s soft core. This method also helps assess the thickness of the cap, which is important since thinner caps are more likely to tear and release clot-forming substances.

Near-infrared spectroscopy (NIS) analyzes light absorption patterns to map the amount of oily lipid within plaque cores. When used alongside ultrasound or optical imaging, it can pinpoint plaques that are particularly lipid-rich and thus more perilous.

Together, these advanced imaging modalities offer complementary perspectives on the same condition, measuring size, demonstrating structure, and unveiling the chemical makeup within plaques.

PCSK9 and Risky Plaques

In the GLAGOV trial, nearly 1,000 patients who were treated with statins had their coronary plaques assessed using intravascular ultrasound. Incorporating evolocumab resulted in a noticeable decrease in the percentage of plaque within the artery walls, with over half of the participants showing a real decline in plaque volume.

A subsequent study named HUYGENS utilized optical coherence tomography and ultrasound in patients having experienced a non-ST elevation myocardial infarction. Adding evolocumab to statins not only thickened the protective cap but also reduced the lipid arc within plaques compared to a placebo.

The PACMAN-AMI trial investigated the PCSK9 blocker alirocumab in 300 patients post-acute myocardial infarction. Serial imaging revealed that alirocumab alongside high-intensity statin treatment reduced plaque burden, minimized the lipid-rich core, and increased cap thickness in arteries that hadn’t caused the initial heart attack.

For individuals with familial hypercholesterolemia, a genetic condition leading to lifelong high LDL levels, the ARCHITECT trial tracked over 100 patients on alirocumab and strong statins. Over a span of about a year and a half, overall plaque burden in the coronary system diminished, with unstable fibrofatty and necrotic core portions shrinking while more stable fibrous and calcified tissues emerged.

The Importance of Plaque Changes

Cardiologists pay close attention to aspects like large lipid cores and very thin fibrous caps alongside high levels of inflammation since these characteristics can indicate a likelihood of plaque rupture. Such risky plaques may be located in arteries that appear mildly narrowed on standard angiograms, yet they are often the ones that rupture, leading to clots.

Current imaging research suggests that PCSK9 inhibitors can transition plaques from this high-risk profile to a more stable, quiescent state. In these studies, plaques generally showed a tendency to shrink, become more fibrous, and feature thicker coverings less prone to splitting.

These changes in plaque composition align with expectations when LDL levels are substantially lowered for extended periods. The imaging findings link alterations in blood profiles to tangible changes in plaques, clarifying the clinical advantages of intensive treatment.

Moreover, because these imaging studies follow the same group of patients over time, they tie reductions in LDL closely to observable signs of plaque improvement in those arteries. This understanding helps explain why aggressive treatment, sometimes started just days after a heart attack, can influence long-term risks.

Insights from Artery Imaging

These investigations emphasize the importance of evaluating both the appearance of arteries and the nature of the plaque present. A slightly narrowed artery predominantly containing soft lipid with a thin cap can pose greater risks than a more narrowed artery made up of dense, fibrous, and calcified tissue.

Researchers are now examining whether noninvasive scans, informed by plaque characteristics such as low-density areas or changes in surrounding fat, can identify individuals most in need of aggressive LDL reduction.

If feasible, this approach may lead doctors to customize PCSK9 therapy not merely based on cholesterol metrics but on the underlying biological properties of each patient’s plaque.

Nonetheless, PCSK9 inhibitors still tend to be expensive and are typically reserved for high-risk individuals who fail to achieve LDL targets through other modalities. Imaging could enhance decision-making by pinpointing patients whose plaques might remain hazardous despite seemingly satisfactory standard treatments.

Ongoing trials are probing the timing and intensity of these drugs’ use following heart attacks, assessing if imaging endpoints should help guide future clinical recommendations. As more findings surface, artery imaging may increasingly assist in showing when plaques have truly stabilized and when further interventions are necessary.

The study can be found in Current Atherosclerosis Reports.