- A new study suggests that combination therapy of rosuvastatin and ezetimibe resulted in a greater reduction in coronary plaque volume than atorvastatin alone.
- The combination treatment also reduced LDL cholesterol more than atorvastatin alone.
- There was also a greater decrease in total coronary plaque volume and non-calcified plaque when using combined treatment.
- Although the results suggest that aggressive cholesterol reduction can reduce and stabilize existing plaque, more research is needed to determine whether these changes reduce the risk of heart attacks, strokes and other cardiovascular events.
Although atherosclerosis is often considered a progressive disease, reducing LDL cholesterol can help reduce existing plaque buildup and the risk of atherosclerotic cardiovascular disease.
Now, a new study suggests that intensive cholesterol-lowering treatment combining two drugs may reduce plaque buildup in the heart’s arteries more effectively than high-dose statin therapy alone, which could help reverse some of the arterial damage associated with atherosclerosis.
The study, published in
Additionally, the 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, more research is needed to determine whether these improvements in arterial plaque translate into fewer heart attacks, strokes, and other cardiovascular events.
The randomized clinical trial included 104 Danish adults with stable chest pain and significant coronary artery disease. Participants had coronary artery narrowing of more than 50%, confirmed by coronary computed tomography angiography (CTA), and none had previously taken statins.
The researchers randomly assigned participants to one of two treatment groups for 18 months. This included the standard intensive statin treatment group, which received 40 milligrams (mg) of atorvastatin per day, or those who received a more intensive combination treatment of rosuvastatin 40 mg per day and ezetimibe 10 mg per day.
Atorvastatin and rosuvastatin are statins that reduce the amount of cholesterol produced by the liver. Ezetimibe works differently by reducing the absorption of cholesterol in the intestine. The combination of the two drugs can therefore reduce 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 plaque volume.
Researchers found that participants receiving rosuvastatin and ezetimibe experienced significantly greater reductions in LDL cholesterol than those taking atorvastatin alone.
LDL cholesterol levels decreased by 65% in the combination therapy group, from an average of 127.4 milligrams per deciliter (mg/dL) to 42.5 mg/dL. In comparison, participants receiving atorvastatin alone experienced a 38% reduction in their LDL cholesterol levels.
These differences were also accompanied by a greater reduction in coronary plaque volume, with reductions of 21.1% in those receiving combined treatment and 13.6% in those receiving atorvastatin alone.
“The main explanation is probably the greater reduction in LDL-C, rather than a specific effect of the drugs themselves,” explained the study’s lead author, Martin Bødtker Mortensen, MD, PhD, clinical associate professor at the Department of Clinical Medicine and Cardiology at Aarhus University. Medical news today.
“The combination achieved an average LDL-C of approximately 1.1 mmol/L, compared to 1.8 mmol/L with atorvastatin alone. This translated into significantly greater plaque regression,” he said.
“Atherosclerosis is not necessarily an irreversible disease. Our results demonstrate that substantial regression is possible, particularly when intensive treatment is initiated in statin-naïve patients. It is important to note that lower LDL-C levels are consistently associated with greater regression,” explained Mortensen.
“The most important finding is that coronary atherosclerosis can regress significantly 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 in total plaque volume.”
—Martin Bødtker Mortensen, MD
The differences were also apparent when the researchers looked at noncalcified plaque. Some forms of this plaque are more vulnerable to rupture, which can trigger blood clots and potentially cause a heart attack.
The volume of noncalcified plaque decreased by 28.2% in the combination treatment group, compared to 20% in the atorvastatin group. Additionally, 51 of 52 participants receiving combination therapy experienced a reduction in the volume of non-calcified plaque, compared to 39 participants in the standard treatment group.
“Noncalcified plaques are generally more biologically active and are considered the high-risk plaque component,” Mortensen noted. “The substantial reduction in noncalcified plaque suggests that intensive LDL-C reduction significantly alters the most dangerous part of the underlying disease process, rather than simply slowing plaque progression.”
Interestingly, the researchers observed a slight increase in the volume of calcified plaque in both treatment groups. However, this does not necessarily indicate that atherosclerosis is getting worse.
As cholesterol-rich plaque becomes more stable, its composition may change. Lipid-rich material may decrease while calcium deposits become greater. This process is associated with plaque stabilization, which may reduce the risk of plaque rupture.
Therefore, changes in plaque composition may be just as important as changes in overall plaque volume when evaluating the effects of cholesterol-lowering therapy. The results suggest that intensive reduction of LDL cholesterol could not only reduce the volume of plaque in the coronary arteries, but also change its composition.
The results of the FLOWPROMOTE clinical trial add to growing evidence that more aggressive reduction of LDL cholesterol can produce significant 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 decrease, potentially improving the arterial condition.
However, the results should be interpreted with some caution. The trial included only 104 participants, all of whom had established coronary artery disease and had never taken statins before. Therefore, the results may not apply equally to people with different cardiovascular risk profiles or to 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 results, it remains unclear whether the greater reductions seen 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, because treatment decisions will depend on the person’s cardiovascular risk, LDL cholesterol level, medical history and response to existing treatment.
Nonetheless, the trial provides additional evidence that more intensive cholesterol management may help reverse some of the plaque buildup associated with coronary artery disease. Larger, longer-term studies will be needed to determine whether these improvements translate into a significant reduction in cardiovascular events.
“Our results reinforce the importance of achieving low LDL-C levels in patients with established coronary artery disease. They also suggest that early initiation of intensive treatment may be particularly important, before plaques 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 key strength of the FLOWPROMOTE study was the use of strict and consistent rules for CT scans every time a patient was tested. This ensured that the images were high quality and reliable enough to accurately track the evolution of arterial plaque over time.
He added that additional studies as part of this project are underway to show what types of plaque can shrink, how quickly this happens and how the composition of the plaque affects the effectiveness of the treatment.
Gn Health
