Ezetimibe's Efficacy in Elderly Patients with High LDL Cholesterol

A study of ezetimibe, a lipid-lowering drug, among elderly Japanese patients with elevated LDL cholesterol level found that ezetimibe 10 mg/day in addition to dietary counseling reduced atherosclerotic cardiovascular events compared to the counseling alone.

Results of the EWTOPIA 75 study were presented during a late-breaking session at the American Heart Association’s Scientific Sessions 2018 in Chicago, IL, by Yasuyoshi Ouchi, MD, PhD, Federation of National Public Service Personnel, Mutual Aid Associations Toranomon Hospital, Tokyo, Japan, and professor emeritus, University of Tokyo.

“A major finding of the study was that lipid-lowering monotherapy with ezetimibe prevented the occurrence of a composite of atherosclerotic cardiovascular events in patients aged greater than or equal to 75 years with elevated LDL cholesterol level who had no history of coronary artery disease,” said Ouchi.

The hazard ratio for this endpoint was .659 (95% CI, .504-.862; P = .002). The composite primary endpoint was composed of sudden cardiac death, fatal myocardial infarction, nonfatal myocardial infarction, coronary revascularization, fatal stroke, and/or nonfatal stroke.

The study included 3796 patients with LDL-C > 140 mg/dL and ≥1 cardiovascular risk (eg, diabetes, hypertension, smoking, low high-density lipoprotein cholesterol levels, high triglyceride levels, history of cerebral infarction, or peripheral artery disease) who were randomized to the ezetimibe group (n = 1898) or the control group (n = 1898).

In the end, 1716 and 1726 participants were included in the final analysis. At baseline, participants had a mean age of 80.7±4.8 years (range, 75 to 104) and a body mass index (BMI) of 23.4±3.6. Most participants were female (74%) and had hypertension (78.0%). Additionally, 22.8% had diabetes.

In addition to the composite primary endpoint, the study measured numerous secondary endpoints. Ouchi reported that the incidence of fatal and nonfatal cardiovascular events was significantly lower in the ezetimibe group and had a hazard ratio (HR) of .602 (95% CI, .370-.979; P = .041).

Another secondary endpoint, fatal and nonfatal cerebrovascular events, was lower for the ezetimibe group, though not statistically significantly (HR .781; 95% CI .549-1.112; P = .171). All-cause mortality was actually observed to be higher in the ezetimibe group, though also not significantly (HR 1.087; 95% CI .885-1.337; P = .427).

“The result obtained in this study is the first evidence suggesting that the primary prevention of atherosclerotic cardiovascular events is possible by lipid-lowering therapy for eligible older patients aged ≥75 years or older,” said Ouchi.

The study was limited by it’s PROBE (prospective, randomized, open-label, blinded-endpoint) design, which did not incorporate a placebo arm and in which health care providers were not blinded. However, Ouchi noted that the primary and secondary endpoints were objective measures “in which investigator’s subjective judgments were not allowed.”

The presentation, “Ezetimibe in Prevention of Cerebro- and Cardiovascular Events in Middle- to High-risk, Elderly (75 Years Old or Over) Patients With Elevated LDL-cholesterol: A Multicenter, Randomized, Controlled, Open-label Trial,” was given at the American Heart Association Scientific Sessions 2018 in Chicago, IL.