There is no single “new drug to unblock arteries,” but several recently approved and experimental therapies are genuinely shrinking arterial plaque or preventing it from worsening in ways that were not possible a decade ago. The treatments generating the most attention fall into a few categories: injectable cholesterol-lowering drugs that target PCSK9, a twice-yearly shot called inclisiran, a gene-editing therapy called VERVE-102 that may work with a single dose, an old anti-inflammatory pill (colchicine) repurposed for heart disease, and drugs aimed at entirely new targets like lipoprotein(a). The landscape is broader and stranger than most people expect, and some of the most promising approaches are still in animal studies or early human trials.
How Plaque Regression Works
Before getting into specific drugs, it helps to understand what “unblocking” an artery actually means at a biological level. The buildup inside artery walls is not like a clog in a pipe that you can snake out. It is a complex structure made of cholesterol, dead cells, immune cells, fibrous tissue, and sometimes calcium. Making it safer involves several overlapping processes: pulling lipids out of the plaque, calming the inflammatory immune cells inside it, thickening the fibrous cap that keeps the plaque from rupturing, and sometimes increasing stable calcification that acts like a shell.
Plaque stabilization and regression are not simply the reverse of plaque growth. They involve lipid removal from the artery wall, a halt in inflammatory cell activity, and a structural remodeling that makes the plaque less likely to crack open and trigger a heart attack or stroke.
PCSK9 Inhibitors and Inclisiran
The drugs closest to what most people picture when they hear “new drug to unblock arteries” are the PCSK9-targeting therapies. PCSK9 is a protein your liver makes that destroys the receptors responsible for clearing LDL cholesterol from your blood. Block that protein, and more receptors survive to pull LDL out of circulation. Two injectable antibodies, evolocumab and alirocumab, have been available since 2015 and have shown they reduce cardiovascular events in large trials.
A meta-analysis of imaging studies found that PCSK9 inhibitors significantly reduced the percentage of artery wall occupied by plaque, thickened the protective fibrous cap overlying the plaque, and decreased the lipid content inside it.
Inclisiran takes a different route to the same destination. Instead of blocking the PCSK9 protein after it has been made, inclisiran is a small interfering RNA that prevents the liver from producing PCSK9 in the first place. It cuts circulating LDL cholesterol by roughly half when added to statin therapy.
The practical appeal of inclisiran is the dosing schedule. After two starter doses, you get an injection just twice a year, which sidesteps the daily-pill compliance problem that plagues statin therapy. Early evidence from imaging substudies suggests that the LDL lowering achieved with inclisiran-containing regimens stabilizes atherosclerotic plaques, as measured by reduced lipid content inside the plaque wall.
A One-Time Gene Edit
If twice-yearly injections still sound like too much maintenance, the most radical approach in the pipeline is a one-and-done gene edit. VERVE-102 is an investigational base-editing therapy that permanently inactivates the PCSK9 gene in liver cells. In an early-phase human trial, a single infusion at the highest dose tested reduced PCSK9 levels by about 88% and LDL cholesterol by about 62%, with the effects appearing durable through at least a year of follow-up.
The therapy packages a base-editor protein and a guide RNA inside a lipid nanoparticle designed to home in on liver cells. It does not cut DNA the way older CRISPR tools do; instead, it chemically converts a single letter in the PCSK9 gene, disabling it. The concept is breathtaking: rather than taking a drug for years, you could receive one IV infusion and have permanently lower cholesterol. But the technology is still in small, early trials, and long-term safety data do not yet exist. A permanent genetic change in your liver is not something you can undo if problems emerge later.
Bempedoic Acid for People Who Cannot Take Statins
Not everyone tolerates statins. Muscle pain drives a meaningful fraction of patients to stop taking them, and for those people, options were limited until recently. Bempedoic acid is an oral pill that blocks cholesterol production at a step upstream of where statins work. Because the enzyme it targets is active mainly in the liver and not in muscle tissue, it tends to cause fewer muscle-related side effects.
In clinical trials of nearly 14,000 high-risk patients with statin intolerance, bempedoic acid reduced major cardiovascular events by about 13% and cut LDL cholesterol by roughly 20% when combined with existing therapy. When researchers looked at total cardiovascular events rather than just the first one per patient, the benefit was even larger: a 20% reduction overall, with particularly strong reductions in heart attacks and the need for coronary procedures.
Bempedoic acid is not as powerful as a high-intensity statin or a PCSK9 inhibitor, but it fills an important gap. It is now available by prescription, often combined with ezetimibe in a single pill, and represents a real option for the statin-intolerant population that cardiologists have long struggled to treat.
Colchicine and the Inflammation Angle
One of the more surprising entries on this list is colchicine, a drug derived from the autumn crocus plant that has been used for gout for centuries. Atherosclerosis is fundamentally an inflammatory disease, and inflammation inside plaques is what makes them dangerous. The idea that dampening that inflammation could prevent heart attacks has been tested in several ways, and low-dose colchicine is the approach that has crossed into routine clinical use.
In the LoDoCo2 trial of patients with stable coronary disease, low-dose colchicine reduced the primary composite of cardiovascular death, heart attack, stroke, or urgent need for a coronary procedure by about 31% compared to placebo. The rate of events dropped from roughly 9.6% in the placebo group to 6.8% in the colchicine group.
A review in the Journal of the American College of Cardiology noted that the magnitude of benefit from colchicine was actually larger than what has been seen in recent secondary-prevention trials of additional cholesterol-lowering drugs, which is a striking finding for a medication that costs pennies per pill.
Colchicine does not lower cholesterol at all. It works by calming the immune cells that drive plaque instability. Newer anti-inflammatory strategies under investigation include drugs that block interleukin-6, inhibitors of the NLRP3 inflammasome (a molecular alarm system inside immune cells), and low-dose interleukin-2, which nudges the immune system toward a more tolerant state.
Targeting Lipoprotein(a)
Lipoprotein(a), often written Lp(a), is a cholesterol particle whose blood level is almost entirely determined by your genes. You cannot meaningfully lower it with diet or exercise, and statins barely budge it. Elevated Lp(a) is an independent risk factor for heart disease, and an estimated one in five people worldwide has levels high enough to matter. Until recently, there was nothing to do about it.
Pelacarsen is an antisense drug that blocks the liver from making the key protein component of Lp(a). In a mid-stage trial, it reduced Lp(a) concentrations by 80% or more with a favorable safety profile. Several other RNA-based drugs targeting the same protein, including olpasiran, zerlasiran, and lepodisiran, are in development and work by slightly different mechanisms but achieve similar dramatic reductions.
The critical question none of these trials has answered yet is whether lowering Lp(a) actually prevents heart attacks and strokes. A large outcomes trial of pelacarsen is underway, and results are expected in the next few years. If positive, Lp(a)-lowering drugs would represent the first entirely new cardiovascular risk factor to become treatable with medication, and they would matter most for the millions of people whose Lp(a) is high through no fault of their own.
Evinacumab for Severe Genetic Cholesterol Disorders
Some people are born with mutations that cause extremely high cholesterol from childhood. Homozygous familial hypercholesterolemia is the most severe form, and even aggressive statin therapy combined with other drugs often fails to bring LDL down to safe levels. Evinacumab is a monoclonal antibody that targets a protein called ANGPTL3, which regulates how the body processes fats through a pathway that is largely independent of LDL receptors.
In a trial published in the New England Journal of Medicine, evinacumab reduced LDL cholesterol by about 47% in patients with homozygous familial hypercholesterolemia, compared to a slight increase in the placebo group. That translates to an absolute drop of over 130 mg/dL, which is dramatic for a population where nothing else works well enough.
Evinacumab is approved under the brand name Evkeeza and is used specifically for this rare condition. It is not a general-purpose cholesterol drug, but for the small population that needs it, it is genuinely life-changing.
Semaglutide’s Unexpected Cardiovascular Benefits
Semaglutide, best known as Ozempic and Wegovy, was developed for diabetes and obesity, but its cardiovascular effects have turned out to be significant in their own right. In the SELECT trial of over 17,000 people with obesity and existing cardiovascular disease but without diabetes, semaglutide reduced the composite of cardiovascular death, heart attack, or stroke by 20% compared to placebo.
The mechanisms behind this benefit are still being worked out. Weight loss alone likely explains part of it, but semaglutide also appears to reduce inflammation, improve blood vessel function, and have direct effects on the heart. Whether it changes the plaques themselves, as opposed to reducing the metabolic environment that makes plaques dangerous, is an active area of imaging research. For people with both obesity and heart disease, semaglutide is increasingly viewed as a cardiovascular drug that happens to also cause weight loss, rather than the other way around.
Experimental Frontiers
Beyond the drugs that are approved or in late-stage trials, several genuinely experimental approaches are worth knowing about because they represent fundamentally different strategies for dealing with arterial plaque.
One line of research focuses on cholesterol efflux, the process by which cholesterol is pulled out of plaque and shipped back to the liver. CSL112 is an infusion of reconstituted apolipoprotein A-I (the main protein in HDL, or “good” cholesterol) that rapidly remodels HDL particles into forms that are highly active at extracting cholesterol from artery walls. It is being tested in patients who have just had a heart attack, when plaque instability is at its peak.
Another approach uses nanotechnology. Phospholipid nanoparticles have been engineered to bind to cholesterol crystals inside plaques and dissolve them while simultaneously calming the inflammatory macrophages that make plaques unstable. In mouse models, these nanoparticles accumulated in plaques, reduced their size, and improved their stability.
Researchers are also investigating whether the body’s own inflammation-resolving molecules could be harnessed therapeutically. In healthy tissue, inflammation shuts itself down through specialized pro-resolving mediators derived from omega-3 fatty acids and other lipids. In advanced atherosclerotic plaques, these mediators are deficient, and the inflammation never fully resolves. Early animal studies using biomimetic nanocarriers loaded with these pro-resolving molecules have shown they can shift immune cells in plaques from an aggressive inflammatory state to a reparative one.
Perhaps the most conceptually bold idea is an atherosclerosis vaccine. In animal models, vaccines engineered to trigger antibodies against PCSK9 have produced sustained cholesterol reductions and smaller plaques. One experimental vaccine using a modified chimeric PCSK9 protein lowered circulating PCSK9 and total cholesterol in mice over 20 weeks and significantly reduced lipid plaque buildup in the aorta. These are proof-of-concept studies only, and human trials are still in the future, but a vaccine that could provide long-lasting cardiovascular protection with periodic boosters would be transformative if it worked.
The Gut Microbiome Connection
A more unexpected research direction involves the bacteria in your gut. Certain gut microbes convert dietary nutrients like choline and carnitine into trimethylamine, which the liver then oxidizes into TMAO, a molecule associated with accelerated atherosclerosis. Compounds that inhibit either the bacterial enzyme that produces trimethylamine or the liver enzyme that converts it to TMAO have reduced TMAO levels in animal studies and shown potential for stabilizing existing plaques.
These inhibitors are still preclinical, but the concept is appealing because they would target a root cause of plaque progression that current drugs ignore entirely. The idea that a pill targeting your gut bacteria could protect your arteries sounds improbable, but the biochemical logic is solid, and several research groups are pursuing it.
Why Drugs Alone Are Not the Full Story
Even with all these advances, it is worth being realistic about what pharmacotherapy can and cannot do. Revascularization procedures, whether stenting or bypass surgery, remain necessary for patients with severe blockages causing symptoms or acute heart attacks. A study comparing outcomes over five years found that both bypass surgery and stenting reduced vessel-related events by roughly a third to nearly half compared to medication alone in patients with significant coronary disease.
Drugs and procedures are not competing strategies so much as complementary ones. The new medications are most powerful as tools for stabilizing plaques so they do not rupture, preventing new blockages from forming, and reducing the residual risk that persists even after a stent or bypass. They are less likely to make an existing severe blockage disappear entirely, though meaningful plaque volume reductions have been documented with aggressive lipid lowering.
Cost and Access Remain Major Barriers
The promise of these drugs runs headfirst into the reality of cost. PCSK9 inhibitor injections can cost thousands of dollars per year. Inclisiran’s pricing, while somewhat lower, is still substantial. Gene-editing therapies like VERVE-102 would likely carry enormous upfront costs if approved. A systematic review of cost-effectiveness studies in developing countries found that PCSK9 inhibitors remain largely unaffordable outside of specific high-risk subgroups or wealthier nations, and that price reductions, tiered pricing, and pooled procurement strategies will be essential to make these advances accessible globally.
Bempedoic acid and colchicine stand out partly because they are relatively inexpensive. Colchicine in particular is generic and costs almost nothing, which makes its cardiovascular benefits especially valuable from a public health perspective. The next few years will likely see a widening gap between what is medically possible and what most of the world can afford, and closing that gap will require deliberate policy choices alongside continued scientific progress.
How Plaque Changes Are Measured
You might wonder how researchers know a drug is actually shrinking or stabilizing plaque. The answer involves imaging technologies threaded directly into coronary arteries during catheterization. Intravascular ultrasound measures plaque volume but has a resolution of about 150 to 200 micrometers, which is too coarse to assess thin fibrous caps that can be as thin as 65 micrometers. Optical coherence tomography uses light instead of sound and achieves a resolution of 15 to 20 micrometers, making it precise enough to measure cap thickness and identify vulnerable features.
A third technique, near-infrared spectroscopy, detects the lipid content of plaques by analyzing how tissue absorbs specific wavelengths of light. Together, these tools allow researchers to track not just whether a plaque is getting smaller, but whether it is becoming structurally safer. The imaging substudies built into many of the trials discussed here are what give scientists confidence that cholesterol lowering is doing more than changing a blood test number; it is physically remodeling the disease inside artery walls.