- A new study suggests that a combination therapy of rosuvastatin plus ezetimibe resulted in a greater reduction in coronary plaque volume than atorvastatin alone.
- Combination therapy also reduced LDL cholesterol more than atorvastatin alone.
- There was also a larger decrease in total coronary plaque volume and noncalcified plaque when using combination therapy.
- Although the findings suggest that aggressive cholesterol lowering can shrink and stabilize existing plaque, further research is necessary to determine whether these changes reduce the risk of heart attacks, strokes, and other cardiovascular events.
Cholesterol-lowering treatments can help reduce levels of low-density lipoprotein (LDL) cholesterol, which contributes to atherosclerosis, or plaque buildup in the arteries.
Reducing coronary plate volume is important because it can help improve blood flow, stabilize existing platelets, and potentially lower the risk of coronary artery disease (CAD), heart attack, stroke, and other cardiovascular complications.
Although atherosclerosis is often considered a progressive condition, lowering LDL cholesterol may help reduce existing plaque buildup and the risk of atherosclerotic cardiovascular disease.
Now, a new study suggests that an intensive cholesterol-lowering treatment combining two medications may shrink plaque buildup in the heart’s arteries more effectively than high dose statin therapy alone, which could help reverse some of the artery damage associated with atherosclerosis.
The study, published in
Additionally, combination therapy also produced greater reductions in total plaque volume and noncalcified plaque, a type of fatty deposit that may be more vulnerable to rupture.
However, further research is necessary to determine whether these improvements in artery plaque translate into fewer heart attacks, strokes, and other cardiovascular events.
How did the researchers compare cholesterol treatments?
The randomized clinical trial included 104 adults in Denmark who had stable chest pain and significant CAD. Participants had coronary artery narrowing of more than 50%, confirmed through coronary computed tomography angiography (CTA), and none had previously taken statins.
Researchers randomly assigned participants to one of two treatment groups for 18 months. This included the standard intensive statin treatment group, which received atorvastatin 40 milligrams (mg) daily, or those who received a more intensive combination treatment of rosuvastatin 40 mg daily alongside ezetimibe 10 mg daily.
Atorvastatin and rosuvastatin are statins, which reduce the amount of cholesterol produced by the liver. Ezetimibe works differently by reducing cholesterol absorption in the intestine. Combining the two medications can therefore lower LDL cholesterol through complementary mechanisms.
Participants underwent coronary CTA before treatment, after 9 months, and at the end of the 18-month study period to assess changes in plate volume.
Combination therapy produced greater plaque regression
The researchers found that participants receiving rosuvastatin and ezetimibe experienced substantially greater reductions in LDL cholesterol than those taking atorvastatin alone.
LDL cholesterol levels decreased by 65% in the combination therapy group, falling from an average of 127.4 milligrams per deciliter (mg/dL) to 42.5 mg/dL. By comparison, participants receiving atorvastatin alone experienced a 38% reduction in LDL cholesterol.
These differences were also accompanied by greater reductions in coronary plaque volume, with reductions of 21.1% among those receiving combination therapy and 13.6% among those receiving atorvastatin alone.
“The main explanation is likely the greater LDL-C reduction, rather than a specific effect of the drugs themselves,” lead study author Martin Bødtker Mortensen, MD, PhD, Clinical Associate Professor in the Department of Clinical Medicine Cardiology at Aarhus University, explained to Medical News Today.
“The combination achieved an average LDL-C of approximately 1.1 mmol/L compared with 1.8 mmol/L with atorvastatin alone. This translated into significantly greater plaque regression,” he said.
“Atherosclerosis is not necessarily an irreversible disease. Our findings demonstrate that substantial regression is possible, particularly when intensive treatment is initiated in previously statin-naive patients. Importantly, lower achieved LDL-C levels were consistently associated with greater regression,” Mortensen further explained.
“The most important finding is that coronary atherosclerosis can regress substantially with intensive LDL-C lowering. We observed a 21% reduction in total plaque volume and a 28% reduction in noncalcified plaque volume after 18 months of more intensive treatment. Remarkably, 90% of patients experienced regression of total plaque volume.”
—Martin Bødtker Mortensen, MD
Reductions in noncalcified plaque with combo therapy
The differences were also apparent when researchers examined noncalcified plaque. Some forms of this plaque are more vulnerable to rupture, which can trigger blood clot formation and potentially cause a heart attack.
Noncalcified plaque volume decreased by 28.2% in the combination therapy group, compared with 20% in the atorvastatin group. Additionally, 51 out of 52 participants receiving combination therapy experienced a reduction in noncalcified plaque volume, compared with 39 participants in the standard treatment group.
“Noncalcified plaques are generally more biologically active and considered the ‘high-risk’ component of plaques,” Mortensen noted. “The substantial reduction in noncalcified plaque suggests that intensive LDL-C lowering substantially modifies the more dangerous part of the underlying disease process, rather than simply slowing plaque progression.”
Why did calcified plaque increase?
Interestingly, researchers observed a modest increase in calcified plaque volume in both treatment groups. However, this does not necessarily indicate that atherosclerosis was worsening.
As cholesterol-rich plaque becomes more stable, its composition can change. Lipid-rich material may decrease while calcium deposits become more prominent. This process is associated with plaque stabilization, which may reduce the likelihood of plaque rupture.
Consequently, changes in plate composition may be just as important as changes in overall plate volume when assessing the effects of cholesterol-lowering treatment. The findings suggest that intensive LDL cholesterol reduction may not only reduce plaque volume in coronary arteries but also alter its composition.
What do the findings mean for people with high cholesterol?
The FLOWPROMOTE clinical trial findings add to the growing evidence that more aggressive LDL cholesterol lowering can produce meaningful changes in coronary artery plaque.
Importantly, they suggest that existing plaque buildup is not necessarily irreversible. With sufficiently intensive cholesterol-lowering treatment, some deposits may shrink, potentially improving arterial condition.
However, the results should be interpreted with some caution. The trial included only 104 participants, all of whom had established CAD and had not previously taken statins. Therefore, the findings may not apply equally to people with different cardiovascular risk profiles or those already receiving cholesterol-lowering treatment.
Additionally, the study measured changes in plaque using coronary imaging rather than directly counting cardiovascular events. Although plaque regression and stabilization are encouraging findings, it remains unclear whether the greater reductions observed with combination therapy will lead to better long-term clinical outcomes.
The findings also do not mean that everyone with high cholesterol should take two cholesterol-lowering medications, as treatment decisions will depend on a person’s cardiovascular risk, LDL cholesterol levels, medical history, and response to existing treatment.
Still, the trial provides further evidence that more intensive cholesterol management may help reverse some of the plaque buildup associated with CAD. Larger, longer-term studies will be needed to determine whether these improvements translate into meaningful reductions in cardiovascular events.
“Our findings reinforce the importance of achieving low LDL-C levels in patients with established coronary disease. They also suggest that early initiation of intensive treatment may be particularly important, before platelets become extensively calcified. However, further studies are needed to establish how these imaging changes translate into clinical outcomes.”
—Martin Bødtker Mortensen, MD
Mortensen said a greatest strength of the FLOWPROMOTE study was the use of strict, consistent rules for CT scans every time a patient was tested. This ensured the images were high quality and reliable enough to accurately track how artery plaque changed over time.
He added that additional studies from this project are underway to show which types of plaque can shrink, how quickly that happens, and how plaque composition affects treatment effectiveness.
