Effectiveness of the addition of ezetimibe to ongoing statin therapy in modifying lipid profiles and attaining low-density lipoprotein cholesterol goals in older and elderly patients: subanalyses of data from a randomized, double-blind, placebo-controlled trial.

BACKGROUND

The Ezetimibe Add-on to Statin for Effectiveness (EASE) trial examined the effectiveness and safety profile of ezetimibe (EZE) added to ongoing statin therapy in 3030 patients with low-density lipoprotein cholesterol (LDL-C) levels exceeding National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP 111) goals.

OBJECTIVE

Because people aged > 65 years are at increased risk for development of coronary heart disease (CHD), these subgroup analyses of data from the EASE trial were conducted to determine the extent of change in LDL-C levels and attainment of NCEP ATP III LDL-C goals with the addition of EZE to ongoing statin therapy in patients aged 65 to 74 years (the older group) and > or = 75 years (the elderly group).

METHODS

In the multicenter (299 sites), community-based, double-blind, placebo-controlled EASE trial, patients were randomly assigned in a 2:1 ratio to receive EZE 10 mg/d or placebo in addition to their ongoing statin therapy for 6 weeks. The primary efficacy end point was the percent reduction in LDL-C levels, and the principal secondary end point was the proportion of patients achieving NCEP ATP III target LDL-C levels. The effects of the addition of EZE on additional lipid and lipoprotein measures and high-sensitivity C-reactive protein were also examined, as was tolerability. Study analyses were performed in the modified intent-to-treat population.

RESULTS

This subgroup analysis included data from 841 patients in the older age group (579 EZE + statin, 262 placebo + statin), which constituted 27.8% of the overall EASE population, and 466 in the elderly group (307 EZE + statin, 159 placebo + statin), which constituted 15.4% of the overall EASE population. The former group included 436 (51.8%) men and 405 (48.2%) women, with a mean (SD) age of 69.2 (3.0) years; the latter group included 227 (48.7%) men and 239 (51.3%) women, with a mean age of 78.5 (3.2) years. The characteristics of the 2 groups were comparable at baseline. In the older group, 717 (85.3%) had CHD or a CHD risk equivalent, as did 421 (90.3%) of those in the elderly group. Thirty-two patients in the older group and 17 in the elderly group discontinued the study. The reasons for discontinuation included clinical adverse events (n = 23), withdrawal of consent (n = 15), loss to follow-up (n = 4), protocol deviation (n = 2), and other reasons (n = 5). EZE + statin significantly reduced LDL-C compared with placebo + statin (older group: mean [SE] treatment difference, -25.1% [1.4]; P < 0.001; elderly group: treatment difference, -22.0% [1.8]; P < 0.001). The LDL-Glowering effects of treatment were consistent in the 2 groups. EZE + statin therapy significantly improved other lipid parameters (triglycerides, non high density lipoprotein cholesterol, and total cholesterol, P < 0.001 in both age groups; high-density lipoprotein cholesterol, P < 0.03 in the older group only) and high-sensitivity C-reactive protein levels compared with EZE + placebo (P < 0.03). The attainment of LDL-C goals also was significantly increased with EZE + statin compared with placebo + statin (older group: 72.3% vs 18.9%, respectively; odds ratio [OR] = 14.59; 95% CI, 9.55 to 22.28; P < 0.001; elderly group: 73.3% vs 18.9%; OR = 13.44; 95% CI, 7.72 to 23.41; P < 0.001). EZE + statin therapy was well tolerated by patients in both age groups, with a safety profile comparable to that of placebo + statin.

CONCLUSIONS

In these older and elderly patients, many of them at high risk for CHD, EZE added to ongoing statin therapy was well tolerated and was an effective treatment option for improving lipid profiles and attainment of LDL-C goals. Adding EZE improved rates of attainment of NCEP ATP III LDL-C goals without increases in the dose or potency of statin therapy. Further studies are necessary to determine whether these results can be generalized to other older and elderly populations.