Luc Missault

Lipid‐altering efficacy of ezetimibe/simvastatin 10/20 mg compared with rosuvastatin 10 mg in high‐risk hypercholesterolaemic patients inadequately controlled with prior statin monotherapy – The IN‐CROSS study

Aims:  To evaluate the efficacy of switching from a previous statin monotherapy to ezetimibe/simvastatin (EZE/SIMVA) 10/20 mg vs. rosuvastatin (ROSUVA) 10 mg.

Lipid-altering efficacy of switching to ezetimibe/simvastatin 10/20 mg versus rosuvastatin 10 mg in high-risk patients with and without metabolic syndrome

Metabolic syndrome (MetS) is a clustering of atherosclerotic coronary heart disease risk factors. This post-hoc analysis compared the effects of switching to ezetimibe/simvastatin 10/20 mg or rosuvastatin 10 mg in a cohort of 618 high-risk hypercholesterolaemic patients with (n=368) and without (n=217) MetS who had previously been on statin monotherapy. Patients were randomised 1:1 to double-blind ezetimibe/simvastatin 10/20 mg or rosuvastatin 10 mg for 6 weeks. Least squares mean percent change from baseline and 95% confidence intervals in lipid efficacy parameters were calculated for the population and within subgroups. Treatment with ezetimibe/simvastatin was significantly more effective than rosuvastatin at lowering low-density lipoprotein cholesterol, total cholesterol, non- high-density lipoprotein cholesterol, and apolipoprotein B (all p<0.001). No significant differences in treatment effects were seen between the presence and absence of MetS. In this post-hoc analysis of high-risk hypercholesterolaemic patients the lipid-reducing effects of ezetimibe/simvastatin or rosuvastatin were not altered significantly by the presence of MetS.

Lipid‐Altering Efficacy of Ezetimibe/Simvastatin 10/20 mg Compared to Rosuvastatin 10 mg in High‐Risk Patients with and without Type 2 Diabetes Mellitus Inadequately Controlled Despite Prior Statin Monotherapy

AIMS This post hoc analysis compared the effects of switching to ezetimibe/simvastatin 10/20 mg (EZE/SIMVA) or rosuvastatin 10 mg (ROSUVA) in uncontrolled high-risk hypercholesterolemic patients with/without type 2 diabetes mellitus (T2DM) despite statin monotherapy. METHODS Patients (n = 618) at high risk for coronary vascular disease with elevated LDL-C ≥100 and ≤190 mg/dL despite use of statins were randomized 1:1 to double-blind EZE/SIMVA 10/20 mg or ROSUVA 10 mg for 6 weeks. Patients were classified as having T2DM based on ≥1 of the following: diagnosis of T2DM, antidiabetic medication, or FPG ≥126 mg/dL. This analysis evaluated percent changes from baseline in lipids among patients with (n = 182) and without T2DM (n = 434). RESULTS EZE/SIMVA was more effective than ROSUVA at lowering LDL-C, TC, non-HDL-C, and apo B in the overall study population and within both subgroups. Numerically, greater between-treatment reductions in LDL-C, TC, non-HDL-C, and apo B were seen in patients with T2DM versus those without T2DM. A significant interaction (P= 0.015) was seen for LDL-C indicating that patients with T2DM achieved larger between-group reductions versus those without T2DM. CONCLUSIONS Switching to EZE/SIMVA 10/20 mg versus ROSUVA 10 mg provided superior lipid reductions in patients with/without T2DM.

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

ObjectiveThis 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.MethodsPatients 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.ResultsSignificant 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.ConclusionsCompared 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 RegistrationRegistered at ClinicalTrials.gov: NCT00479713

Switching from statin monotherapy to ezetimibe/simvastatin or rosuvastatin modifies the relationships between apolipoprotein B, LDL cholesterol, and non-HDL cholesterol in patients at high risk of coronary disease

OBJECTIVE To evaluate relationships between apolipoprotein B (Apo B), LDL cholesterol (LDL-C), and non-HDL-C in high-risk patients treated with lipid-lowering therapy. DESIGN AND METHODS This post-hoc analysis calculated LDL-C and non-HDL-C levels corresponding to an Apo B of 0.9 g/L following treatment with 1) statin monotherapy (baseline) and 2) ezetimibe/simvastatin 10/20mg or rosuvastatin 10mg (study end). The percentages of patients reaching LDL-C, non-HDL-C, and Apo B targets were calculated at study end. RESULTS After switching to ezetimibe/simvastatin or rosuvastatin, the LDL-C and non-HDL-C corresponding to Apo B=0.9 g/L were closer to the more aggressive LDL-C and non-HDL-C goals (1.81 and 2.59 mmol/L, respectively). Only slightly >50% of the patients who reached minimum recommended LDL-C or non-HDL-C at study end also had an Apo B level <0.9 g/L with both treatments. CONCLUSION The use of Apo B for monitoring the efficacy of lipid-altering therapy would likely lead to more stringent criteria for lipid lowering.