"Combination Therapy Effective in Controlling 'Bad Cholesterol' in Patients Aged 75 and Older"

by Lee Gwanju

Published 05 Apr.2023 11:06(KST)

Statin+Ezetimibe Combination
Low Side Effects and Excellent Efficacy

A study has found that moderate-intensity statin and ezetimibe combination therapy is effective in controlling low-density lipoprotein (LDL) cholesterol in elderly patients aged 75 and older with atherosclerotic cardiovascular disease.

[Photo by Yonsei Medical Center]

A research team led by Professors Kim Joong-sun, Lee Yong-jun, and Lee Sang-hyup from the Department of Cardiology at Yonsei University Severance Hospital, along with Professor Heo Jeong-ho from the Department of Cardiology at Kosin University Hospital, announced on the 5th that in patients aged 75 and older with atherosclerotic cardiovascular disease, moderate-intensity statin and ezetimibe combination therapy was more effective in controlling LDL cholesterol levels compared to conventional high-dose statin monotherapy, and the incidence of treatment discontinuation due to drug side effects was also lower.

For patients with cardiovascular disease, it is important to maintain the so-called "bad cholesterol," LDL cholesterol, at low levels of 55 mg/dL or 70 mg/dL or below to prevent recurrence of myocardial infarction, stroke, or cardiogenic death. Statin therapy, which inhibits LDL cholesterol synthesis in the liver, is the most commonly used method to lower LDL cholesterol. However, in elderly patients, continuous high-dose statin treatment increases the risk of side effects such as muscle pain and liver dysfunction, limiting long-term medication use and making it difficult to achieve sufficient complication suppression effects.

The research team conducted an age-based subgroup analysis of the RACING study, previously published by the Severance Hospital cardiology team in the international journal The Lancet, which demonstrated the superiority of moderate-intensity statin and ezetimibe combination therapy in controlling LDL cholesterol compared to high-intensity statin monotherapy. From February 2017 to December 2018, 574 elderly patients aged 75 and older with atherosclerotic cardiovascular diseases such as myocardial infarction, stroke, and peripheral artery disease were enrolled from 26 hospitals in Korea to compare the treatment effects of high-intensity statin monotherapy and moderate-intensity statin and ezetimibe combination therapy.

[Provided by Yonsei Medical Center]

After random assignment to the two treatment regimens and a 3-year follow-up, the average LDL cholesterol levels and incidences of cardiovascular death, stroke, and cardiovascular events were analyzed. The median LDL cholesterol level during the observation period was 57 mg/dL in the combination therapy group and 64 mg/dL in the monotherapy group, showing superior LDL cholesterol reduction in the combination therapy group. Regarding cardiovascular death, stroke occurrence, and cardiovascular event rates, the combination therapy group had 10.6%, which was not significantly different from the monotherapy group’s 12.3%.

The rate of drug discontinuation due to side effects or intolerance was significantly lower in the combination therapy group at 2.3%, compared to 7.2% in the monotherapy group. Notably, in terms of the risk of diabetes development associated with long-term statin use, which has recently gained attention, the combination therapy group showed a lower incidence of 10% compared to 18.7% in the monotherapy group during the follow-up period.

Professor Kim Joong-sun stated, "In elderly patients aged 75 and older with atherosclerotic cardiovascular disease, moderate-intensity statin and ezetimibe combination therapy effectively controlled LDL cholesterol compared to high-intensity statin monotherapy, and also showed lower rates of drug discontinuation due to side effects and diabetes risk. We expect this to be a safer treatment alternative for elderly patients."