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Ezetimibe/simvastatin 10/40 mg versus atorvastatin 40 mg in high cardiovascular risk patients with primary hypercholesterolemia: a randomized, double-blind, active-controlled, multicenter study.

Hing Ling PK, Civeira F, Dan AG, Hanson ME, Massaad R, De Tilleghem Cle B, Milardo C, Triscari J - Lipids Health Dis (2012)

Bottom Line: Switching to ezetimibe/simvastatin resulted in significantly greater changes in LDL-C (-26.81% vs.-11.81%), total cholesterol (-15.97% vs.-7.73%), non-HDL-C (-22.50% vs.-10.88%), Apo B (-17.23% vs.-9.53%), and Apo A-I (2.56% vs.-2.69%) vs. doubling the atorvastatin dose (all p ≤ 0.002), but not HDL-C, triglycerides, or hs-CRP.The overall safety profile appeared generally comparable between treatment groups.In high cardiovascular risk subjects with hypercholesterolemia already treated with atorvastatin 20 mg but not at LDL-C < 2.59 mmol/L, switching to combination ezetimibe/simvastatin 10/40 mg provided significantly greater LDL-C lowering and greater achievement of LDL-C targets compared with doubling the atorvastatin dose to 40 mg.

View Article: PubMed Central - HTML - PubMed

Affiliation: School of Medicine and Health Sciences, Monash University, 80100 Johor Bahru, Malaysia. pkhling@yahoo.co.uk

ABSTRACT

Background: A considerable number of patients with severely elevated LDL-C do not achieve recommended treatment targets, despite treatment with statins. Adults at high cardiovascular risk with hypercholesterolemia and LDL-C ≥ 2.59 and ≤ 4.14 mmol/L (N = 250), pretreated with atorvastatin 20 mg were randomized to ezetimibe/simvastatin 10/40 mg or atorvastatin 40 mg for 6 weeks. The percent change in LDL-C and other lipids was assessed using a constrained longitudinal data analysis method with terms for treatment, time, time-by-treatment interaction, stratum, and time-by-stratum interaction. Percentage of subjects achieving LDL-C < 1.81 mmol/L, < 2.00 mmol/L, or < 2.59 mmol/L was assessed using a logistic regression model with terms for treatment and stratum. Tolerability was assessed.

Results: Switching to ezetimibe/simvastatin resulted in significantly greater changes in LDL-C (-26.81% vs.-11.81%), total cholesterol (-15.97% vs.-7.73%), non-HDL-C (-22.50% vs.-10.88%), Apo B (-17.23% vs.-9.53%), and Apo A-I (2.56% vs.-2.69%) vs. doubling the atorvastatin dose (all p ≤ 0.002), but not HDL-C, triglycerides, or hs-CRP. Significantly more subjects achieved LDL-C < 1.81 mmol/L (29% vs. 5%), < 2.00 mmol/L (38% vs. 9%) or < 2.59 mmol/L (69% vs. 41%) after switching to ezetimibe/simvastatin vs. doubling the atorvastatin dose (all p < 0.001). The overall safety profile appeared generally comparable between treatment groups.

Conclusions: In high cardiovascular risk subjects with hypercholesterolemia already treated with atorvastatin 20 mg but not at LDL-C < 2.59 mmol/L, switching to combination ezetimibe/simvastatin 10/40 mg provided significantly greater LDL-C lowering and greater achievement of LDL-C targets compared with doubling the atorvastatin dose to 40 mg. Both treatments were generally well-tolerated.

Trial registration: Registered at clinicaltrials.gov: NCT00782184.

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Related in: MedlinePlus

Estimate of Treatment Difference in percent Change from Baseline in LDL-C (LS Mean ± 95% CI) Within Each Level of Specific Subgroup at Study Endpoint After 6 Weeks of Treatment (Full Analysis Set Population).
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Figure 3: Estimate of Treatment Difference in percent Change from Baseline in LDL-C (LS Mean ± 95% CI) Within Each Level of Specific Subgroup at Study Endpoint After 6 Weeks of Treatment (Full Analysis Set Population).

Mentions: After 6 weeks of treatment, ezetimibe/simvastatin 10/40 mg resulted in significantly greater reductions from treated baseline in LDL-C levels compared with doubling the dose of atorvastatin to 40 mg (-26.8% vs -11.8%; p < 0.001 [Figure 2]). The estimated between-treatment difference was -15.0% (95% confidence interval [CI]: -21.15, -8.84) in favor of ezetimibe/simvastatin 10/40 mg therapy. The greater efficacy of the ezetimibe/simvastatin 10/40 mg treatment in reducing LDL-C was consistent across prespecified subgroups (Figure 3). Significantly more subjects attained all prespecified LDL-C targets with ezetimibe/simvastatin 10/40 mg vs atorvastatin 40 mg after 6 weeks of treatment (all p < 0.001; Figure 4). The percentage of subjects reaching LDL-C < 1.81 mmol/L (70 mg/dL), < 2.00 mmol/L (77 mg/dL) and < 2.59 mmol/L (100 mg/dL), respectively, was 29.1% vs 4.8% in the ezetimibe/simvastatin 10/40 mg group vs the atorvastatin 40 mg group; 38.5% vs. 8.7% in the ezetimibe/simvastatin 10/40 mg group vs the atorvastatin 40 mg group; and 69.2% vs 41.3% in the ezetimibe/simvastatin 10/40 mg group vs. the atorvastatin 40 mg group.


Ezetimibe/simvastatin 10/40 mg versus atorvastatin 40 mg in high cardiovascular risk patients with primary hypercholesterolemia: a randomized, double-blind, active-controlled, multicenter study.

Hing Ling PK, Civeira F, Dan AG, Hanson ME, Massaad R, De Tilleghem Cle B, Milardo C, Triscari J - Lipids Health Dis (2012)

Estimate of Treatment Difference in percent Change from Baseline in LDL-C (LS Mean ± 95% CI) Within Each Level of Specific Subgroup at Study Endpoint After 6 Weeks of Treatment (Full Analysis Set Population).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3306831&req=5

Figure 3: Estimate of Treatment Difference in percent Change from Baseline in LDL-C (LS Mean ± 95% CI) Within Each Level of Specific Subgroup at Study Endpoint After 6 Weeks of Treatment (Full Analysis Set Population).
Mentions: After 6 weeks of treatment, ezetimibe/simvastatin 10/40 mg resulted in significantly greater reductions from treated baseline in LDL-C levels compared with doubling the dose of atorvastatin to 40 mg (-26.8% vs -11.8%; p < 0.001 [Figure 2]). The estimated between-treatment difference was -15.0% (95% confidence interval [CI]: -21.15, -8.84) in favor of ezetimibe/simvastatin 10/40 mg therapy. The greater efficacy of the ezetimibe/simvastatin 10/40 mg treatment in reducing LDL-C was consistent across prespecified subgroups (Figure 3). Significantly more subjects attained all prespecified LDL-C targets with ezetimibe/simvastatin 10/40 mg vs atorvastatin 40 mg after 6 weeks of treatment (all p < 0.001; Figure 4). The percentage of subjects reaching LDL-C < 1.81 mmol/L (70 mg/dL), < 2.00 mmol/L (77 mg/dL) and < 2.59 mmol/L (100 mg/dL), respectively, was 29.1% vs 4.8% in the ezetimibe/simvastatin 10/40 mg group vs the atorvastatin 40 mg group; 38.5% vs. 8.7% in the ezetimibe/simvastatin 10/40 mg group vs the atorvastatin 40 mg group; and 69.2% vs 41.3% in the ezetimibe/simvastatin 10/40 mg group vs. the atorvastatin 40 mg group.

Bottom Line: Switching to ezetimibe/simvastatin resulted in significantly greater changes in LDL-C (-26.81% vs.-11.81%), total cholesterol (-15.97% vs.-7.73%), non-HDL-C (-22.50% vs.-10.88%), Apo B (-17.23% vs.-9.53%), and Apo A-I (2.56% vs.-2.69%) vs. doubling the atorvastatin dose (all p ≤ 0.002), but not HDL-C, triglycerides, or hs-CRP.The overall safety profile appeared generally comparable between treatment groups.In high cardiovascular risk subjects with hypercholesterolemia already treated with atorvastatin 20 mg but not at LDL-C < 2.59 mmol/L, switching to combination ezetimibe/simvastatin 10/40 mg provided significantly greater LDL-C lowering and greater achievement of LDL-C targets compared with doubling the atorvastatin dose to 40 mg.

View Article: PubMed Central - HTML - PubMed

Affiliation: School of Medicine and Health Sciences, Monash University, 80100 Johor Bahru, Malaysia. pkhling@yahoo.co.uk

ABSTRACT

Background: A considerable number of patients with severely elevated LDL-C do not achieve recommended treatment targets, despite treatment with statins. Adults at high cardiovascular risk with hypercholesterolemia and LDL-C ≥ 2.59 and ≤ 4.14 mmol/L (N = 250), pretreated with atorvastatin 20 mg were randomized to ezetimibe/simvastatin 10/40 mg or atorvastatin 40 mg for 6 weeks. The percent change in LDL-C and other lipids was assessed using a constrained longitudinal data analysis method with terms for treatment, time, time-by-treatment interaction, stratum, and time-by-stratum interaction. Percentage of subjects achieving LDL-C < 1.81 mmol/L, < 2.00 mmol/L, or < 2.59 mmol/L was assessed using a logistic regression model with terms for treatment and stratum. Tolerability was assessed.

Results: Switching to ezetimibe/simvastatin resulted in significantly greater changes in LDL-C (-26.81% vs.-11.81%), total cholesterol (-15.97% vs.-7.73%), non-HDL-C (-22.50% vs.-10.88%), Apo B (-17.23% vs.-9.53%), and Apo A-I (2.56% vs.-2.69%) vs. doubling the atorvastatin dose (all p ≤ 0.002), but not HDL-C, triglycerides, or hs-CRP. Significantly more subjects achieved LDL-C < 1.81 mmol/L (29% vs. 5%), < 2.00 mmol/L (38% vs. 9%) or < 2.59 mmol/L (69% vs. 41%) after switching to ezetimibe/simvastatin vs. doubling the atorvastatin dose (all p < 0.001). The overall safety profile appeared generally comparable between treatment groups.

Conclusions: In high cardiovascular risk subjects with hypercholesterolemia already treated with atorvastatin 20 mg but not at LDL-C < 2.59 mmol/L, switching to combination ezetimibe/simvastatin 10/40 mg provided significantly greater LDL-C lowering and greater achievement of LDL-C targets compared with doubling the atorvastatin dose to 40 mg. Both treatments were generally well-tolerated.

Trial registration: Registered at clinicaltrials.gov: NCT00782184.

Show MeSH
Related in: MedlinePlus