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.