Dual inhibition effective and safe in clinical practice: The EASE study

NEW ORLEANS–Adding ezetimibe to stable ongoing statin therapy produced an additional 23% reduction in low-density lipoprotein (LDL) cholesterol levels compared with statin monotherapy. The community-based Ezetimibe Add-On to Statin for Effectiveness (EASE) trial involved 3030 patients. Adding ezetimibe significantly reduced LDL cholesterol levels for every subgroup analyzed: age, sex, race, presence of diabetes, metabolic syndrome, brand of statin, and National Cholesterol Education Program Adult Treatment Panel III (ATP III) risk category.

Several studies have shown that only a minority of patients achieve their LDL cholesterol goals on statin therapy. Inadequate doses and a failure to use combination therapy may be contributing factors.

The EASE trial tested the efficacy and safety of adding ezetimibe 10 mg daily to any statin brand and dose for a population of patients who were not at their ATP III LDL cholesterol goal despite receiving a statin (LDL cholesterol = 123-167 mg/dL). Trial end points were the percent reduction in LDL cholesterol level and the proportion of patients who achieved their LDL cholesterol goal at follow-up.

Patients were randomized to ezetimibe added to their statin or to statin plus placebo in a 2:1 fashion for 6 weeks. Sixty-two percent were on a usual starting dose of a statin. They could not initially be on a lipid-lowering agent other than a statin and had to have alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatinine kinase (CK) levels below 1.5 times the upper limit of normal (ULN). Their mean age was approximately 62 years.

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Principal investigator Thomas A. Pearson, MD, MPH, PhD, Albert D. Kaiser Professor and chair of the Department of Community and Preventive Medicine at the University of Rochester, New York, said patients randomized to ezetimibe had a 25.8% reduction in their LDL cholesterol levels compared with only a 2.7% reduction for patients randomized to placebo ( < .001). Atorvastatin was the most commonly prescribed statin, accounting for almost 40% of the patients.

Patients in all ATP III—defined risk categories benefited from the addition of ezetimibe. Among all subgroups, patients who had <2 coronary heart disease (CHD) risk factors had the highest proportion achieving an LDL cholesterol goal. Among patients with CHD or CHD risk equivalents, almost 70% of those on ezetimibe reached goal compared with 17.3% receiving placebo.

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In addition to LDL cholesterol benefits, ezetimibe was superior to placebo in raising high-density lipoprotein (HDL) levels and in reducing triglyceride, non-HDL cholesterol, and apolipoprotein B levels (all < .001).

Patients tolerated the combination of ezetimibe with a statin as well as a statin alone. The incidence of ALT or AST elevations >3 times the ULN was similar in ezetimibe and placebo groups and did not exceed 0.4%. No CK elevations >10 times the ULN occurred.

Dr Pearson said, "The 23% additional reduction in the LDL goal [when ezetimibe is added to a statin] really compares very favorably with the 6% or 8% reduction one usually gets by doubling the statin dose." He recommended that the combination therapy be considered for patients who have not reached their ATP III LDL goals on statin therapy alone.