CHICAGO – has been provided by the Japanese EWTOPIA 75 trial.
Ezetimibe (Zetia) at 10 mg/day reduced the risk of the primary endpoint, a composite of atherosclerotic cardiovascular events, by 34% compared with a dietary counseling control group over the course of 5 years of followup. Yasuyoshi Ouchi, MD, PhD, reported the findings of the 3,796-patient study at the American Heart Association scientific sessions.
There was also a 40% relative risk reduction for cardiac events in the ezetimibe group. The 22% reduction in cerebrovascular events, however, didn’t achieve statistical significance, and there was no between-group difference in all-cause mortality, said Dr. Ouchi, principal investigator in EWTOPIA 75 and professor emeritus of geriatric medicine at the University of Tokyo.
The landmark randomized clinical trials of lipid-lowering for primary cardiovascular prevention included too few elderly participants to permit assessment of its merits and possible harms in that population. This has left a major evidence gap at a time when in many parts of the world, including the United States, Europe, and Japan, the population over age 75 is growing explosively.
“Along with this population change, the number of patients age 75 and older with hypercholesterolemia has dramatically increased,” Dr. Ouchi continued.
Eligibility for EWTOPIA was restricted to patients who were at least 75 years old, had an LDL of at least 140 mg/dL, no history of CAD, and had at least one high-risk factor, such as diabetes or hypertension. Their mean age at enrollment was 80.7 years. Seventy-four percent of them were women, reflecting the significantly longer life expectancy of Japanese women compared to men.
The study design was open-label with no placebo arm. Dr. Ouchi argued that this was appropriate, given that the components of the primary composite endpoint were “entirely objective”: fatal and nonfatal MI, fatal and nonfatal stroke, sudden cardiac death, and coronary revascularization.
The mean LDL in the ezetimibe group dropped from 162 mg/dL at baseline to 120 mg/dL at 5 years, versus 131 mg/dL in the control group.