A joint study conducted by researchers from Severance Hospital and Korea University Anam Hospital found that moderate-intensity statin combined with ezetimibe effectively controlled low-density lipoprotein (LDL) cholesterol levels with lower risks of medication discontinuation, compared to monotherapy high-dose statin therapies in very high-risk atherosclerosis patients.

Due to the super-aging society and the increase in Westernized diets, the number of patients suffering from myocardial infarction and cerebral infarction is increasing. Moreover, the proportion of ultra-high-risk atherosclerosis patients, who are at high risk of developing severe vascular occlusive diseases due to underlying diseases and arteriosclerosis throughout the body, is also on the rise.

It is important to keep LDL cholesterol low at levels lower than 55 mg/dL or 70 mg/dL to prevent recurrent myocardial infarction, stroke, and cardiovascular death. Statins are most commonly used to inhibit the synthesis of LDL cholesterol in the liver but high doses of statin therapy are associated with a high risk of side effects, including muscle damage, decreased liver function, and elevated blood sugar, making long-term use difficult.

The team led by Professors Kim Jung-sun and  Lee Seung-jun of the Cardiology Department at Severance Hospital and Professors Hong Soon-jun and Cha Jung-joon of the Cardiology Department at Korea University Anam Hospital conducted a patient-risk-based subanalysis of an existing study published in the Lancet journal by researchers from the Cardiology Department at Severance Hospital.

Accordingly, the researchers analyzed the treatment effects of high-intensity statin monotherapy versus moderate-intensity statin-ezetimibe combination therapy in 1,511 patients at a very high risk of atherosclerosis. Ultra-high risk of atherosclerosis was defined as having 12 conditions, including a history of myocardial infarction, comorbid peripheral artery disease, and hypertension. 

After randomization to either treatment regimen, the researchers followed the patients for three years to analyze mean LDL cholesterol levels, the incidence of complications such as heart attack, myocardial infarction, and cerebral infarction, and patient adherence to continuous medication.

Analysis of median LDL cholesterol levels in both groups showed superior LDL cholesterol lowering in the combination arm, with 57 mg/dL in the combination arm and 65 mg/dL in the monotherapy arm. The complication rate of heart attack, myocardial infarction, and cerebral infarction during clinical follow-up was 11.2 percent in the combination group, which was similar to the monotherapy group at 11.7 percent.

In addition, the rate of discontinuation due to adverse drug reactions was lower at 4.6 percent in the combination group compared to 7.7 percent in the monotherapy group, confirming the benefit of continued treatment. 

"We found that moderate-intensity statin-ezetimibe combination therapy effectively controlled LDL cholesterol compared with high-intensity statin monotherapy in ultra-high-risk atherosclerosis patients at high risk for vascular occlusive events, with a lower risk of discontinuation due to adverse events and complications," said Professor Kim. "We look forward to providing more effective treatments for ultra-high-risk atherosclerosis patients." 

The study was published in the international journal, JAMA Cardiology on Aug. 2.