Variability of the LDL-C lowering response to ezetimibe and ezetimibe + statin therapy in hypercholesterolemic patients. Issue 2 (June 2015)

• Record Type: Journal Article
• Authors: Descamps, Olivier; Tomassini, Joanne E.; Lin, Jianxin; Polis, Adam B.; Shah, Arvind; Brudi, Philippe; Hanson, Mary E.; Tershakovec, Andrew M.
• Is Part Of: Atherosclerosis. Volume 240:Issue 2(2015)
• Page Start: 482
• Page End: 489
• Publication Date: 2015-06
• Subjects: Ezetimibe -- Hypercholesterolemia -- LDL-C -- Statin -- Variability; Arteriosclerosis -- Periodicals; Electronic journals; 616.136
• DOI: 10.1016/j.atherosclerosis.2015.03.004
• Languages: English
• ISSNs: 0021-9150

Abstract

Abstract: Objective: We compared the variability of LDL-C-lowering responses to treatment with ezetimibe + statins versus statins in hypercholesterolemic patients. Methods: An analysis of patient-level data pooled from 27 double-blind, placebo and/or active-controlled studies in 21, 671 patients treated with ezetimibe + statins versus statins on first-line (statin-naïve/wash-out) or second-line (on statin, randomized to ezetimibe versus placebo [add-on] or ezetimibe versus uptitrated statin [uptitrate]) for 6–24 wks. Variances (standard deviation [SD], coefficient of variation [CV], and root mean squared error [RMSE] adjusted for various factors) for % change from baseline in LDL-C were compared. Results: In first-line and second-line add-on studies, the variability (SD, RMSE) of % change from baseline in LDL-C was lower in ezetimibe + statin-treated patients versus statin-treated patients, ±covariates. Differences were small but statistically significant due to the large sample size. In second-line uptitrate studies, ezetimibe + statin treatment resulted in greater unadjusted variability (SD) versus statin therapy, while the adjusted variability (RMSE) was significantly lower. Relative variability (CV = SD/mean) was lower for ezetimibe + statins versus statin therapy for all study types, being more pronounced in second-line add-on and uptitrate studies, attributed to larger mean LDL-C reductions for ezetimibe + statins versus statin groups. When assessed by individual study/type, statin brand, potency or dose, the CVs remained lower for ezetimibe + statins versus statins in second-line studies. The SDs showed no consistent trend for either therapy. Conclusion: In hypercholesterolemic patients, the absolute variability of LDL-C-lowering responses to ezetimibe + statins was not greater versus statins alone and appeared lower when adjusted for other factors. Relative variability was lower in patients treated with statins + ezetimibe. A better understanding of the variability of the LDL-C lowering response may help guide clinicians in making therapeutic decisions. Highlights: Variability of LDL-C lowering response to ezetimibe + statins vs statins was compared. Absolute variability was not greater with ezetimibe + statin vs statins. Relative variability was lower for ezetimibe + statin vs statins attributed to larger LDL-C reductions. Variability within subgroups was generally consistent with the full cohort. Ezetimibe added to statins does not increase the variability of LDL-C lowering response.