Ezetimibe Add-on to Statin Therapy for Effectiveness Trial - EASE (Ezetimibe)

Description:

The goal of the trial was to evaluate the efficacy and safety of ezetimibe compared with placebo added to a stable dose of any statin in patients with low-density lipoprotein (LDL) cholesterol exceeding National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III goals.

Hypothesis:

Ezetimibe added to a stable dose of any statin will be associated with a greater reduction in LDL levels compared with placebo added to a stable dose of any statin in patients with LDL cholesterol exceeding NCEP ATP III goals.

Study Design

  • Placebo Controlled
  • Randomized
  • Blinded

Patients Enrolled: 3,030
Mean Follow Up: Six weeks
Mean Patient Age: Mean age 62 years
Female: 48

Patient Populations:

Age ≥18 years, LDL levels above the NCEP ATP guidelines, triglycerides <350 mg/dl, and ability to continue on the statin for the duration of the study

Exclusions:

Use of a lipid-lowering agent other than a statin; hemoglobin >9 in diabetic patients; ALT, AST, or CK ≥1.5 ULN

Primary Endpoints:

Percent change from baseline in LDL cholesterol at treatment end in the overall population and by NCEP ATP III CHD risk category

Drug/Procedures Used:

Patients receiving marketed statins (40% atorvastatin, 29% simvastatin, 22% pravastatin, 10% other) were randomized 2:1 in a double-blind manner to either ezetimibe (10 mg; n=2,020) or matching placebo (n=1,010). Treatment was continued for six weeks. Lipid profiles were assessed at screening, enrollment, and six weeks.

Principal Findings:

A large proportion of patients in the trial had diabetes (38.4%) and metabolic syndrome by NCEP ATP III criteria (60%). Baseline LDL levels were 129 mg/dl in the overall population, 123 mg/dl in the coronary heart disease (CHD) or CHD risk equivalent group, 147 mg/dl in the multiple risk factors group, and 167 mg/dl in the <2 risk factors group.

In the overall study population, a larger percent change from baseline in LDL levels occurred in the ezetimibe arm versus placebo (-25.8 mg/dl vs. -2.7 mg/dl, p<0.001). The follow-up LDL level in the ezetimibe arm was 95 mg/dl. Additionally, a larger percentage of patients in the ezetimibe arm reached target LDL goals (71.0% vs. 20.6%, p<0.001).

Results were similar across the different statin brands and by the prespecified subgroups of age group, gender, and diabetes status. The ezetimibe arm also had a larger reduction in triglycerides (-12.8 mg/dl vs. -1.6 mg/dl, p<0.001) and a larger increase in high-density lipoprotein (HDL) levels (1.3 mg/dl vs. -0.8 mg/dl, p<0.001).

Likewise, in the CHD/CHD risk equivalent subgroup, there was a larger percent change from baseline in LDL levels in the ezetimibe arm versus placebo (-25.1 mg/dl vs. -1.1 mg/dl, p<0.001) and a larger percentage of patients in the ezetimibe arm reaching target LDL goals (69.5% vs. 17.3%, p<0.001).

Similar results were observed in both the multiple risk factor subgroup and the <2 CHD risk factor subgroup. In the multiple risk factor subgroup, the percent change from baseline in LDL levels was -23.8 mg/dl in the ezetimibe arm and -4.1 mg/dl for placebo (p<0.001). The frequency of reaching target LDL goals was higher in the ezetimibe arm (75.1% vs. 32.2%, p<0.001). In the <2 CHD risk factor subgroup, the percent change from baseline in LDL levels was -25.7 mg/dl in the ezetimibe arm and -5.8 mg/dl for placebo (p<0.001), with target LDL goals reached in 90.7% and 52.4%, respectively (p<0.001).

There were no increases in the frequency of alanine aminotransferase (ALT) ≥3 times upper limit of normal (ULN) (0.4% for ezetimibe vs. 0.2% for placebo), aspartate aminotransferase (AST) ≥3 times ULN (0.2% vs. 0.1%), or creatine kinase (CK) ≥10 times ULN (0 in both groups).

Interpretation:

Among patients with LDL cholesterol exceeding NCEP ATP III goals and on statin therapy, additional treatment with ezetimibe was associated with a larger reduction in LDL cholesterol and a greater number of patients meeting LDL target goals compared with placebo, with no additional safety issues. The presenter noted that the 23% larger reduction in LDL levels was higher than the 6-8% reduction usually observed by doubling the statin dose.

The present trial adds to the growing body of studies showing an added benefit with ezetimibe in addition to statin therapy. Earlier trials used a selected statin rather than any statin, as in the present trial, which represents a more "real-world" look at the use of concomitant ezetimibe therapy.

References:

Presented by Dr. Thomas Pearson at the American College of Cardiology Annual Scientific Session, March 2004.

Pearson TA, Denke MA, McBride PE, Battisti WP, Brady WE, Palmisano J. A community-based, randomized trial of ezetimibe added to statin therapy to attain NCEP ATP III goals for LDL cholesterol in hypercholesterolemic patients: the ezetimibe add-on to statin for effectiveness (EASE) trial. Mayo Clin Proc. 2005 May;80(5):587-95.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Homozygous Familial Hypercholesterolemia, Lipid Metabolism, Nonstatins, Statins

Keywords: Intestine, Small, Creatine Kinase, Cholesterol, LDL, Coronary Disease, Heptanoic Acids, Hypercholesterolemia, Cholesterol, Dietary, Simvastatin, Vitamins, Metabolic Syndrome X, Pyrroles, Liver Function Tests, C-Reactive Protein, Azetidines, Pravastatin, Triglycerides, Diabetes Mellitus, Myalgia


< Back to Listings