Variability of the LDL-C lowering response to ezetimibe and ezetimibe + statin therapy in hypercholesterolemic patients.
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.


CONCLUSIONS
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.
Centre de Recherche Médicale de Jolimont, 159, Rue Ferrer, 7100 Haine Saint-Paul, Belgium. Electronic address: olivierdescamps@hotmail.com.
Olivier
O
Descamps
Merck & Co., Inc., 2000 Galloping Hill Rd, Kenilworth, NJ 07033, USA. Electronic address: joanne_tomassini@merck.com.
Joanne E
JE
Tomassini
Merck & Co., Inc., 2000 Galloping Hill Rd, Kenilworth, NJ 07033, USA. Electronic address: jianxin.lin@merck.com.
Jianxin
J
Lin
Merck & Co., Inc., 2000 Galloping Hill Rd, Kenilworth, NJ 07033, USA. Electronic address: adam.polis@merck.com.
Adam B
AB
Polis
Merck & Co., Inc., 2000 Galloping Hill Rd, Kenilworth, NJ 07033, USA. Electronic address: arvind.shah@merck.com.
Arvind
A
Shah
Merck & Co., Inc., 2000 Galloping Hill Rd, Kenilworth, NJ 07033, USA. Electronic address: philippe.brudi@merck.com.
Philippe
P
Brudi
Merck & Co., Inc., 2000 Galloping Hill Rd, Kenilworth, NJ 07033, USA. Electronic address: mary.hanson@merck.com.
Mary E
ME
Hanson
Merck & Co., Inc., 2000 Galloping Hill Rd, Kenilworth, NJ 07033, USA. Electronic address: andrew.tershakovec@merck.com.
Andrew M
AM
Tershakovec
D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood*; D015536:Down-Regulation; D004338:Drug Combinations; D019317:Evidence-Based Medicine; D000069438:Ezetimibe / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D013997:Time Factors; D016896:Treatment Outcome
D000924:Anticholesteremic Agents; D015415:Biomarkers; D008078:Cholesterol, LDL; D004338:Drug Combinations; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000069438:Ezetimibe
Ezetimibe; Hypercholesterolemia; LDL-C; Statin; Variability