AHA 2018 — Ezetimibe reduces risk of major cardiac events in Japanese elderly

  • Hao Cheng, MD
  • Conference Reports
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  • This study provides the first evidence that primary prevention of atherosclerotic cardiovascular events is possible with lipid-lowering therapy in eligible patients ≥75 years old.

Why this matters

  • A growing population of ≥75-year-olds in many countries dramatically increases the rates of hypercholesterolemia.
  • However, there are no randomized controlled trials on the efficacy of LDL-cholesterol (C)-lowering therapy in patients aged 75 years of age with elevated LDL-C. 

Study design

  • Prospective, randomized open-label blinded endpoint (PROBE) study on Japanese older adults (75) without cardiovascular disease.
  • Patients included if they have LDL-C ≥140 and 1 of the following: diabetes mellitus, hypertension, low HDL-cholesterolemia, hypertriglyceridemia, smoking, previous documented history of cerebral infarction, or peripheral artery disease.
  • Patients were randomly assigned to dietary counseling only vs dietary counseling and ezetimibe 10 mg/day.
  • Primary endpoint was a composite of atherosclerotic cardiovascular events including sudden cardiac death, myocardial infarction, percutaneous coronary intervention/coronary artery bypass grafting, and stroke.

Key results

  • 3796 patients were included in the final analysis.
  • Ezetimibe cohort showed significant decrease of primary endpoint HR (CI 95%): 0.659 (0.504-0.862), P=.002.
  • Ezetimibe cohort did not show significant benefits in:
    • Cerebrovascular events HR (CI 95%): 0.781 (0.549-1.112), P=.171.
    • All-cause mortality HR (CI 95%): 1.087 (0.885-1.337), P=.427.


  • PROBE design, so no placebo.

Expert comment

  • "[Are the results] generalizable to other non-Japanese populations? . . . There's a possibility that the Japanese may have different biological response to LDL-lowering. There are different NPC1L1 polymorphisms in the Japanese population, which we're inhibiting with ezetimibe. But that would affect efficacy and we do have data from Japanese PRECISE-IVUS of really quite remarkable regression with ezetimibe added to atorvastatin, so it could be some biological effect." — Jennifer Robinson, MD, MPH, Professor, Departments of Epidemiology & Medicine, University of Iowa.