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Influence of metabolic syndrome factors and insulin resistance on the efficacy of ezetimibe/simvastatin and atorvastatin in patients with metabolic syndrome and atherosclerotic coronary heart disease risk.

Rosen JB, Ballantyne CM, Hsueh WA, Lin J, Shah AK, Lowe RS, Tershakovec AM - Lipids Health Dis (2015)

Bottom Line: Metabolic syndrome (MetS) and insulin resistance (IR) are increasing in prevalence, are associated with higher risk for coronary heart disease (CHD), and may potentially influence the responses to lipid-altering drug therapy.Triglycerides, very-LDL-C, and hs-CRP results were more variable but similar between treatment groups.The magnitude of lipid-altering effects produced by each treatment regimen was generally similar across all MetS and IR subgroups.

View Article: PubMed Central - PubMed

Affiliation: Clinical Research of South Florida, Coral Gables, FL, USA. jrosen@crsouthflorida.com.

ABSTRACT

Background: Metabolic syndrome (MetS) and insulin resistance (IR) are increasing in prevalence, are associated with higher risk for coronary heart disease (CHD), and may potentially influence the responses to lipid-altering drug therapy. This study evaluated the effects of MetS factors (abdominal obesity, depleted high-density lipoprotein cholesterol [HDL-C], and elevated triglycerides, blood pressure, and fasting glucose) and IR on ezetimibe/simvastatin and atorvastatin treatment efficacy in patients with MetS.

Methods: This post-hoc analysis of a multicenter, 6-week, double-blind, randomized, parallel group study of 1128 subjects with hypercholesterolemia, MetS, and moderately high/high CHD risk evaluated the effects of baseline MetS factors/IR on percent change from baseline in lipids, apolipoproteins, and high-sensitivity C-reactive protein (hs-CRP), after treatment with the usual starting doses of ezetimibe/simvastatin (10/20 mg) versus atorvastatin (10 mg, 20 mg) and next higher doses (10/40 mg versus 40 mg).

Results: Ezetimibe/simvastatin and atorvastatin efficacy was generally consistent across MetS factor/IR subgroups. Ezetimibe/simvastatin produced greater incremental percent reductions in LDL-C, non-HDL-C, apolipoprotein B, total cholesterol, and lipoprotein ratios for all subgroups, and larger percent increases in HDL-C and apolipoprotein AI for all but non-obese and HDL-C ≥ 40 mg/dL subgroups than atorvastatin at the doses compared. Triglycerides, very-LDL-C, and hs-CRP results were more variable but similar between treatment groups.

Conclusion: The magnitude of lipid-altering effects produced by each treatment regimen was generally similar across all MetS and IR subgroups. Ezetimibe/simvastatin produced greater percent reductions in most lipid fractions than atorvastatin at the dose comparisons studied, and all treatments were generally well tolerated. (Registered at clinicaltrials.gov: NCT00409773).

No MeSH data available.


Related in: MedlinePlus

Percent change from baseline in lipid, lipoprotein, and hs-CRP by treatment and metabolic syndrome/IR subgroup. Error bars = standard error. Arrows indicate percent change from baseline reported for the overall study population [13], with associated value given below the measured parameter for each treatment group. A10/20/40 = atorvastatin 10/20/40 mg; Apo = apolipoprotein; BP = blood pressure [systolic blood pressure (diastolic blood pressure)]; E10/S20(40) = ezetimibe 10 mg/simvastatin 20(40) mg; FG = fasting glucose; HDL-C = high density lipoprotein cholesterol; IR = Homeostasis Model Assessment of Insulin Resistance tertiles; hs-CRP = high-sensitivity C-reactive protein, LDL-C = low- density lipoprotein cholesterol; Ob = abdominal obesity (waist circumference ≥40 inches for males or ≥35 inches for females); TG = triglycerides
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Fig1: Percent change from baseline in lipid, lipoprotein, and hs-CRP by treatment and metabolic syndrome/IR subgroup. Error bars = standard error. Arrows indicate percent change from baseline reported for the overall study population [13], with associated value given below the measured parameter for each treatment group. A10/20/40 = atorvastatin 10/20/40 mg; Apo = apolipoprotein; BP = blood pressure [systolic blood pressure (diastolic blood pressure)]; E10/S20(40) = ezetimibe 10 mg/simvastatin 20(40) mg; FG = fasting glucose; HDL-C = high density lipoprotein cholesterol; IR = Homeostasis Model Assessment of Insulin Resistance tertiles; hs-CRP = high-sensitivity C-reactive protein, LDL-C = low- density lipoprotein cholesterol; Ob = abdominal obesity (waist circumference ≥40 inches for males or ≥35 inches for females); TG = triglycerides

Mentions: Ezetimibe/simvastatin (10/20 mg, 10/40 mg) and atorvastatin (10, 20, 40 mg) therapy produced relatively consistent lipid-altering effects across all metabolic syndrome factor and insulin resistant subgroups, which were similar in magnitude to those previously reported for the overall study population (Fig. 1) [14]. All treatments produced significant reductions from baseline in LDL-C, non-HDL-C, total cholesterol, apo B, triglycerides, and lipid/lipoprotein ratios (total cholesterol:HDL-C, LDL-C:HDL-C, apo B:apo AI, non-HDL-C:HDL-C, data not shown) for all subgroups. VLDL-C (data not shown) and hs-CRP changes from baseline were also significant for most subgroup evaluations and consistent with the changes observed for the full cohort. Increases in HDL-C were observed for all subgroups except two (subjects receiving atorvastatin 10 mg and 20 mg with systolic blood pressure <130 mm Hg [diastolic <85 mm Hg], n = 11 and 21, respectively) and most changes were nominally significant. Elevations in apo AI were smaller in magnitude than HDL-C, and most were not significantly different from baseline (data not shown). When comparing ezetimibe/simvastatin 10/20 mg with atorvastatin 10 mg or 20 mg, and ezetimibe/simvastatin 10/40 mg with atorvastatin 40 mg, treatment with ezetimibe/simvastatin produced generally greater percent reductions from baseline in LDL-C, non-HDL-C, Apo B, total cholesterol, and lipoprotein ratios (data not shown) for all but four subgroup comparisons, with between treatment differences ranging from 0.4 to 27.6 % (Table 2); atorvastatin 40 mg produced greater reductions than ezetimibe/simvastatin 10/40 mg for LDL-C by 2.0 %, LDL-C:HDL-C by 4.5 % and apoB:apoA1 by 1.3 % for subjects with waist circumferences <40/35 inches, and similar reductions in apoB (0.1 %) for subjects with blood pressure <130/85 mm Hg. Assessment of the associated 95 % CIs suggest that the lipid-lowering effects of ezetimibe/simvastatin were greater than atorvastatin at the doses compared for most subgroups (Table 2), which is consistent with the significantly greater differences previously reported for the entire cohort (Fig. 1) [14]. When compared with atorvastatin, ezetimibe/simvastatin produced numerically larger percent increases in HDL-C and apo AI for all but three subgroups (non-obese, HDL-C ≥40 mg/dl, and HOMA-IR 2.72-4.81 (Table 2). The percent changes from baseline in VLDL-C (not shown), triglycerides, and hs-CRP were similar for the majority of ezetimibe/simvastatin and atorvastatin comparisons and were consistent with the similar treatment effects seen for the overall study.Fig. 1


Influence of metabolic syndrome factors and insulin resistance on the efficacy of ezetimibe/simvastatin and atorvastatin in patients with metabolic syndrome and atherosclerotic coronary heart disease risk.

Rosen JB, Ballantyne CM, Hsueh WA, Lin J, Shah AK, Lowe RS, Tershakovec AM - Lipids Health Dis (2015)

Percent change from baseline in lipid, lipoprotein, and hs-CRP by treatment and metabolic syndrome/IR subgroup. Error bars = standard error. Arrows indicate percent change from baseline reported for the overall study population [13], with associated value given below the measured parameter for each treatment group. A10/20/40 = atorvastatin 10/20/40 mg; Apo = apolipoprotein; BP = blood pressure [systolic blood pressure (diastolic blood pressure)]; E10/S20(40) = ezetimibe 10 mg/simvastatin 20(40) mg; FG = fasting glucose; HDL-C = high density lipoprotein cholesterol; IR = Homeostasis Model Assessment of Insulin Resistance tertiles; hs-CRP = high-sensitivity C-reactive protein, LDL-C = low- density lipoprotein cholesterol; Ob = abdominal obesity (waist circumference ≥40 inches for males or ≥35 inches for females); TG = triglycerides
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4559874&req=5

Fig1: Percent change from baseline in lipid, lipoprotein, and hs-CRP by treatment and metabolic syndrome/IR subgroup. Error bars = standard error. Arrows indicate percent change from baseline reported for the overall study population [13], with associated value given below the measured parameter for each treatment group. A10/20/40 = atorvastatin 10/20/40 mg; Apo = apolipoprotein; BP = blood pressure [systolic blood pressure (diastolic blood pressure)]; E10/S20(40) = ezetimibe 10 mg/simvastatin 20(40) mg; FG = fasting glucose; HDL-C = high density lipoprotein cholesterol; IR = Homeostasis Model Assessment of Insulin Resistance tertiles; hs-CRP = high-sensitivity C-reactive protein, LDL-C = low- density lipoprotein cholesterol; Ob = abdominal obesity (waist circumference ≥40 inches for males or ≥35 inches for females); TG = triglycerides
Mentions: Ezetimibe/simvastatin (10/20 mg, 10/40 mg) and atorvastatin (10, 20, 40 mg) therapy produced relatively consistent lipid-altering effects across all metabolic syndrome factor and insulin resistant subgroups, which were similar in magnitude to those previously reported for the overall study population (Fig. 1) [14]. All treatments produced significant reductions from baseline in LDL-C, non-HDL-C, total cholesterol, apo B, triglycerides, and lipid/lipoprotein ratios (total cholesterol:HDL-C, LDL-C:HDL-C, apo B:apo AI, non-HDL-C:HDL-C, data not shown) for all subgroups. VLDL-C (data not shown) and hs-CRP changes from baseline were also significant for most subgroup evaluations and consistent with the changes observed for the full cohort. Increases in HDL-C were observed for all subgroups except two (subjects receiving atorvastatin 10 mg and 20 mg with systolic blood pressure <130 mm Hg [diastolic <85 mm Hg], n = 11 and 21, respectively) and most changes were nominally significant. Elevations in apo AI were smaller in magnitude than HDL-C, and most were not significantly different from baseline (data not shown). When comparing ezetimibe/simvastatin 10/20 mg with atorvastatin 10 mg or 20 mg, and ezetimibe/simvastatin 10/40 mg with atorvastatin 40 mg, treatment with ezetimibe/simvastatin produced generally greater percent reductions from baseline in LDL-C, non-HDL-C, Apo B, total cholesterol, and lipoprotein ratios (data not shown) for all but four subgroup comparisons, with between treatment differences ranging from 0.4 to 27.6 % (Table 2); atorvastatin 40 mg produced greater reductions than ezetimibe/simvastatin 10/40 mg for LDL-C by 2.0 %, LDL-C:HDL-C by 4.5 % and apoB:apoA1 by 1.3 % for subjects with waist circumferences <40/35 inches, and similar reductions in apoB (0.1 %) for subjects with blood pressure <130/85 mm Hg. Assessment of the associated 95 % CIs suggest that the lipid-lowering effects of ezetimibe/simvastatin were greater than atorvastatin at the doses compared for most subgroups (Table 2), which is consistent with the significantly greater differences previously reported for the entire cohort (Fig. 1) [14]. When compared with atorvastatin, ezetimibe/simvastatin produced numerically larger percent increases in HDL-C and apo AI for all but three subgroups (non-obese, HDL-C ≥40 mg/dl, and HOMA-IR 2.72-4.81 (Table 2). The percent changes from baseline in VLDL-C (not shown), triglycerides, and hs-CRP were similar for the majority of ezetimibe/simvastatin and atorvastatin comparisons and were consistent with the similar treatment effects seen for the overall study.Fig. 1

Bottom Line: Metabolic syndrome (MetS) and insulin resistance (IR) are increasing in prevalence, are associated with higher risk for coronary heart disease (CHD), and may potentially influence the responses to lipid-altering drug therapy.Triglycerides, very-LDL-C, and hs-CRP results were more variable but similar between treatment groups.The magnitude of lipid-altering effects produced by each treatment regimen was generally similar across all MetS and IR subgroups.

View Article: PubMed Central - PubMed

Affiliation: Clinical Research of South Florida, Coral Gables, FL, USA. jrosen@crsouthflorida.com.

ABSTRACT

Background: Metabolic syndrome (MetS) and insulin resistance (IR) are increasing in prevalence, are associated with higher risk for coronary heart disease (CHD), and may potentially influence the responses to lipid-altering drug therapy. This study evaluated the effects of MetS factors (abdominal obesity, depleted high-density lipoprotein cholesterol [HDL-C], and elevated triglycerides, blood pressure, and fasting glucose) and IR on ezetimibe/simvastatin and atorvastatin treatment efficacy in patients with MetS.

Methods: This post-hoc analysis of a multicenter, 6-week, double-blind, randomized, parallel group study of 1128 subjects with hypercholesterolemia, MetS, and moderately high/high CHD risk evaluated the effects of baseline MetS factors/IR on percent change from baseline in lipids, apolipoproteins, and high-sensitivity C-reactive protein (hs-CRP), after treatment with the usual starting doses of ezetimibe/simvastatin (10/20 mg) versus atorvastatin (10 mg, 20 mg) and next higher doses (10/40 mg versus 40 mg).

Results: Ezetimibe/simvastatin and atorvastatin efficacy was generally consistent across MetS factor/IR subgroups. Ezetimibe/simvastatin produced greater incremental percent reductions in LDL-C, non-HDL-C, apolipoprotein B, total cholesterol, and lipoprotein ratios for all subgroups, and larger percent increases in HDL-C and apolipoprotein AI for all but non-obese and HDL-C ≥ 40 mg/dL subgroups than atorvastatin at the doses compared. Triglycerides, very-LDL-C, and hs-CRP results were more variable but similar between treatment groups.

Conclusion: The magnitude of lipid-altering effects produced by each treatment regimen was generally similar across all MetS and IR subgroups. Ezetimibe/simvastatin produced greater percent reductions in most lipid fractions than atorvastatin at the dose comparisons studied, and all treatments were generally well tolerated. (Registered at clinicaltrials.gov: NCT00409773).

No MeSH data available.


Related in: MedlinePlus