New review outlines how today's medicines can shrink—and stabilize—dangerous artery plaques
Article by Francisco Epelde in Current Drug Therapy, March 16 2026
Atherosclerotic cardiovascular disease remains one of the world's leading drivers of heart attacks and ischemic strokes, largely because fatty, inflamed plaques can build up inside arteries and eventually rupture. In a new comprehensive review published ahead-of-print in Current Drug Therapy, physician-researcher Francisco Epelde synthesizes evidence showing that modern pharmacologic care is increasingly moving beyond "slowing progression" toward an ambitious but measurable goal: reducing plaque size and transforming plaque composition into a more stable, less rupture-prone form.
The review, Advances in Pharmacologic Strategies to Reduce Atheroma Plaque Size in Atheromatosis: A Comprehensive Review, brings together findings from pivotal randomized trials and imaging studies to map a rapidly expanding therapeutic landscape. Its central message is that plaque regression is no longer a theoretical concept confined to research settings. With aggressive lipid lowering, targeted anti-inflammatory therapy, and selected cardiometabolic interventions, clinicians can increasingly influence both the quantity of atheroma and the biology of the plaque itself—two factors closely tied to cardiovascular risk.
From cholesterol lowering to plaque remodeling
For decades, statins have served as the foundation of prevention because lowering LDL cholesterol reduces future cardiovascular events. The review highlights how intravascular imaging studies helped shift the field: when LDL is lowered sufficiently, coronary plaque burden can plateau and, in some patients, regress. Major trials using intravascular ultrasound (IVUS) helped establish the concept that intensive statin therapy can reduce atheroma volume and improve plaque stability—an early demonstration that medication can modify arterial disease, not just risk factors.
PCSK9 inhibitors: deeper LDL reduction, measurable plaque benefits
A newer generation of lipid-lowering therapies—PCSK9 inhibitors—extends this paradigm by enabling LDL reductions that often exceed what statins achieve alone. In the review's synthesis, PCSK9 inhibitors commonly reduce LDL-C by roughly 50–60%, opening the door to very low LDL targets in high-risk patients.
Beyond the cholesterol numbers, imaging studies show why this matters. Advanced modalities such as IVUS, optical coherence tomography (OCT), and MRI indicate that PCSK9 inhibition can reduce plaque volume and shift plaque structure toward stability—thickening the fibrous cap and shrinking lipid-rich cores that are associated with vulnerability to rupture. This "qualitative" remodeling is particularly relevant because plaque rupture, followed by thrombosis, is the immediate trigger for many acute coronary syndromes.
The review also points to emerging longer-interval options such as inclisiran, an RNA-based therapy designed for infrequent dosing, which could support adherence in real-world practice—while also noting that costs and access remain key constraints for many health systems.
Bempedoic acid: an option when statins are not enough—or not tolerated
For patients who cannot tolerate statins or require additional LDL lowering, the review describes bempedoic acid as a practical adjunct. Because it is activated primarily in the liver, it may reduce muscle-related side effects seen with some statin regimens, while still delivering clinically meaningful LDL reductions. Although direct plaque-imaging data are still emerging, the therapy is positioned as part of an increasingly flexible toolkit for achieving lower LDL levels in more patients.
Inflammation as a second therapeutic lever
Atherosclerosis is not only a lipid storage disease; it is also an inflammatory process. The review highlights anti-inflammatory strategies—such as canakinumab and low-dose colchicine—that reduce cardiovascular events in clinical trials, supporting the idea that suppressing vascular inflammation can complement lipid lowering. Colchicine, in particular, is presented as a cost-effective approach with broad anti-inflammatory effects, though it is not a direct plaque-volume therapy in the same way that intensive lipid lowering can be.
Cardiometabolic drugs: benefits that may extend to plaque biology
Epelde also reviews evidence that drugs initially developed for diabetes and obesity—GLP-1 receptor agonists and SGLT2 inhibitors—confer cardiovascular protection through metabolic, hemodynamic, and anti-inflammatory pathways. While direct imaging evidence for plaque regression remains limited, these agents may promote plaque stabilization indirectly by improving weight, glycemic control, blood pressure, and systemic inflammation.
Why imaging matters for the next phase of prevention
A key implication of the review is methodological: imaging endpoints are increasingly central to evaluating plaque response. Techniques like IVUS, OCT, and MRI can quantify changes in plaque burden and composition, helping researchers and clinicians move from a "one-size-fits-all" approach toward personalization—matching therapy intensity and combinations to a patient's risk profile and disease biology.
Looking ahead: personalized combinations, better access, and outcome-driven trials
While the evidence supports an integrated strategy—aggressive lipid lowering, targeted inflammation control, and adjunct cardiometabolic therapies—the review cautions that many studies rely on surrogate imaging outcomes and short follow-up, and that head-to-head comparisons across novel agents are limited. The next generation of research, the author argues, should prioritize long-term, adequately powered trials that combine imaging and hard clinical outcomes, alongside cost-effectiveness and access considerations so benefits can be realized broadly across diverse healthcare settings.
Article title : Advances in Pharmacologic Strategies to Reduce Atheroma Plaque Size in Atheromatosis: A Comprehensive Review (Francisco Epelde, Parc Taulí Hospital Universitari, Sabadell, Spain)
Read the published article here: https://bit.ly/4uEAdiN
JOURNAL
Current Drug Therapy
DOI: 10.2174/0115748855405974251130161059
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