Ezetimibe/simvastatin 10/20 mg versus rosuvastatin 10 mg in high-risk hypercholesterolemic patients stratified by prior statin treatment potency

Margus Viigimaa, Helena Vaverkova, Michel Farnier, Maurizio Averna, Luc Missault, Mary E Hanson, Qian Dong, Arvind Shah, Philippe Brudi, Margus Viigimaa, Helena Vaverkova, Michel Farnier, Maurizio Averna, Luc Missault, Mary E Hanson, Qian Dong, Arvind Shah, Philippe Brudi

Abstract

Objective: This post-hoc analysis compared the lipid-altering efficacy of Ezetimibe/Simvastatin 10/20 mg (EZ/Simva) versus Rosuvastatin 10 mg (Rosuva) in patients stratified by statin potency/dose prior to randomization.

Methods: Patients with elevated low-density lipoprotein cholesterol (LDL-C) despite prior statin treatment (n=618) were randomized 1:1 to EZ/Simva 10/20 mg or Rosuva 10 mg for 6 weeks. Percent change from baseline in lipids and attainment of lipid targets were assessed within each subgroup (low potency n=369, high potency n=249). Consistency of the treatment effect across subgroups was evaluated by testing for treatment-by-subgroup interaction. No multiplicity adjustments were made.

Results: Significant treatment-by-subgroup interaction occurred for LDL-C (p=0.013), total cholesterol (p=0.025), non-HDL-C (p=0.032), and apolipoprotein B (p=0.016) with greater between-treatment differences in favor of EZ/Simva observed in patients from the high potency stratum vs low potency stratum. Individual and triple target attainment was higher for Eze/Simva compared with Rosuva in both strata.

Conclusions: Compared with Rosuva, switching to EZ/Simva provided greater reductions in LDL-C, total cholesterol, non-HDL-C and apolipoprotein B and higher target attainment in patients on prior statin treatment, regardless of potency, although patients treated with higher potency statins prior to randomization experienced greater between treatment differences in favor of EZ/Simva.

Trial registration: Registered at ClinicalTrials.gov: NCT00479713.

Figures

Figure 1
Figure 1
Percent change in lipid and hs-CRP levels after 6 weeks of treatment in patients treated with low-potency statins* at baseline. *Low potency stratum included: simvastatin 20 mg, pravastatin 40 mg, fluvastatin 80 mg, atorvastatin 10 mg. †Presented as median values. Apo B = apolipoprotein B; E = ezetimibe; hs-CRP = high-sensitivity C-reactive protein; LDL-C = low-density lipoprotein cholesterol; HDL-C = high-density lipoprotein cholesterol; R = rosuvastatin; S = simvastatin; TG = triglycerides; Total C = total cholesterol
Figure 2
Figure 2
Percent change in lipid and hs-CRP levels after 6 weeks of treatment in patients treated with high-potency statins* at baseline. *High potency stratum included: simvastatin 40 mg, atorvastatin 20 mg, rosuvastatin 5 mg †Presented as median values Apo B = apolipoprotein B; E = ezetimibe; LDL-C = low-density lipoprotein cholesterol; HDL-C = high-density lipoprotein cholesterol; hs-CRP = high sensitivity C-reactive protein; R = rosuvastatin; S = simvastatin; TG = triglycerides; Total C = total cholesterol
Figure 3
Figure 3
Percent of patients achieving lipid targets at 6 weeks (treated with low-potency statins† at baseline). *Triple target = LDL-C <100 mg/dL and non-HDL-C <130 mg/dL and Apo B <90 mg/dL †Low potency stratum included: simvastatin 20 mg, pravastatin 40 mg, fluvastatin 80 mg, atorvastatin 10 mg‡Ratio of the predictive odds of attaining target on EZ+Simva versus Rosuvastatin based on the logistic model (fitted within each subgroup) with terms for treatment and baseline values of the variable being modeled. Apo B = apolipoprotein B; E = ezetimibe; LDL-C = low-density lipoprotein cholesterol; non-HDL-C = non-high-density lipoprotein cholesterol; R = rosuvastatin; S = simvastatin
Figure 4
Figure 4
Percent of patients achieving lipid targets at 6 weeks (treated with high-potency statins† at baseline). *Triple target = LDL-C <100 mg/dL and non-HDL-C <130 mg/dL and Apo B <90 mg/dL †High potency stratum included: simvastatin 40 mg, atorvastatin 20 mg, rosuvastatin 5 mg ‡Ratio of the predictive odds of attaining target on EZ+Simva versus Rosuvastatin based on the logistic model (fitted within each subgroup) with terms for treatment and baseline values of the variable being modeled. Apo B = apolipoprotein B; E = ezetimibe; LDL-C = low-density lipoprotein cholesterol; non-HDL-C = non-high-density lipoprotein cholesterol; R = rosuvastatin; S = simvastatin

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