Atorvastatin 10 mg plus ezetimibe versus titration to atorvastatin 40 mg: attainment of European and Canadian guideline lipid targets in high-risk subjects ≥65 years

Abstract

Background: Few clinical studies have focused on the efficacy of lipid-lowering therapies in patients ≥65 years.

Methods: After stabilization on atorvastatin 10 mg, hypercholesterolemic subjects ≥65 years at high/very high risk for CHD and not at LDL-C <1.81 mmol/L (with atherosclerotic vascular disease [AVD]) or <2.59 mmol/L (without AVD) were randomized to ezetimibe 10 mg plus atorvastatin 10 mg or uptitration to atorvastatin 20 mg (6 weeks) followed by uptitration to 40 mg (additional 6 weeks). A post-hoc analysis compared between-group differences in percent attainment of individual and combined LDL-C, non-HDL-C and Apo B targets based on recommendations from 2012 European and Canadian Cardiovascular Society (CCS) guidelines for dyslipidemia treatment.

Results: Atorvastatin 10 mg plus ezetimibe produced significantly greater attainment of LDL-C, non-HDL-C, and Apo B individual and dual/triple targets vs. atorvastatin 20 mg for the entire cohort and very high-risk groups at 6 weeks. After 12 weeks, very high-risk subjects maintained significantly greater achievement of LDL-C <1.8 mmol/L (47% vs. 35%), non-HDL-C <2.6 mmol/L (63% vs. 53%) and Apo B <0.8 g/L (47% vs. 38%) single targets and dual/triple targets with atorvastatin 10 mg plus ezetimibe vs. atorvastatin 40 mg, while attainment of European target for high-risk subjects was generally similar for both treatments. Achievement of Canadian targets was significantly greater with combination therapy vs. atorvastatin 20 mg (6 weeks) or atorvastatin 40 mg (12 weeks).

Conclusions: Atorvastatin 10 mg plus ezetimibe provided more effective treatment than uptitration to atorvastatin 20/40 mg for attainment of most European and Canadian guideline-recommended lipid targets in older at-risk patients.

Trial registration: ClinicalTrials.gov identifier NCT00418834.

Figures

Figure 1

Proportion of subjects achieving targets defined by Canadian guidelines*. Error bars = standard error. *Canadian Cardiovascular Society/Canadian Dyslipidemia guidelines (2012) [4]. † Triple combination includes LDL-C ≤2.0 mmol/L, non-HDL-C ≤2.6 mmol/L, and Apo B ≤0.8 g/L. A, atorvastatin (10, 20 or 40 mg); Apo, apolipoprotein; AVD, atherosclerotic vascular disease; E, ezetimibe 10 mg; LDL-C, low-density lipoprotein cholesterol; non-HDL-C, non-high-density lipoprotein cholesterol.

Figure 2

Proportion of all and high-risk subjects achieving targets defined by European guidelines*. A. All Subjects. B. High-Risk Subjects without AVD. Error bars = standard error. * European Guidelines on cardiovascular disease prevention in clinical practice (version 2012) [12]. † Triple combination includes LDL-C <2.5 mmol/L, non-HDL-C <3.3 mmol/L, and Apo B <1.0 g/L. A, atorvastatin (10, 20 or 40 mg); Apo, apolipoprotein; AVD, atherosclerotic vascular disease; E, ezetimibe 10 mg; LDL-C, low-density lipoprotein cholesterol; non-HDL-C, non-high-density lipoprotein cholesterol.

Figure 3

Proportion of all and very high-risk subjects achieving targets defined by European guidelines*. A. All Subjects. B. Very High-Risk Subjects with AVD. Error bars = standard error. * European Guidelines on cardiovascular disease prevention in clinical practice (version 2012) [12]. † Triple combination includes LDL-C <1.8 mmol/L, non-HDL-C <2.6 mmol/L, and Apo B <0.8 g/L. A, atorvastatin (10, 20 or 40 mg); Apo, apolipoprotein; AVD, atherosclerotic vascular disease; E, ezetimibe 10 mg; LDL-C, low-density lipoprotein cholesterol; non-HDL-C, non-high-density lipoprotein cholesterol.