ezetimibe--simvastatin-drug-combination and Diabetes-Mellitus--Type-1

Topics: Acute Coronary Syndrome; Anticholesteremic Agents; Diabetes Mellitus, Type 1; Drug Combinations; Ezetimibe, Simvastatin Drug Combination; Humans; Hypercholesterolemia; Survival Rate

Patients with diabetes mellitus and cardiovascular disease may not achieve adequate low-density lipoprotein cholesterol (LDL-C) lowering on statin monotherapy, attributed partly to atherogenic dyslipidemia. More intensive LDL-C-lowering therapy can be considered for these patients. A previous randomized, controlled study demonstrated greater LDL-C lowering in diabetic patients with symptomatic cardiovascular disease who switched from simvastatin 20 mg (S20) or atorvastatin 10 mg (A10) to combination ezetimibe/simvastatin 10/20 mg (ES10/20) therapy, compared with statin dose-doubling (to S40 or A20) or switching to rosuvastatin 10 mg (R10). The effect of these regimens on novel biomarkers of atherogenic dyslipidemia (low- and high-density lipoprotein particle number and lipoprotein-associated phospholipase A2 [Lp-PLA2]) was assessed.. Treatment effects on low- and high-density lipoprotein particle number (by NMR) and Lp-PLA2 (by ELISA) were evaluated using plasma samples available from 358 subjects in the study. Switching to ES10/20 reduced low-density lipoprotein-particle number numerically more than did statin dose-doubling and was comparable with R10 (-133.3, -94.4, and -56.3 nmol/L, respectively; P>0.05). Increases in high-density lipoprotein particle number were significantly greater with switches to ES10/20 versus statin dose-doubling (1.5 and -0.5 μmol/L; P<0.05) and comparable with R10 (0.7 μmol/L; P>0.05). Percentages of patients attaining low-density lipoprotein particle number levels <990 nmol/L were 62.4% for ES10/20, 54.1% for statin dose-doubling, and 57.0% for R10. Switching to ES10/20 reduced Lp-PLA2 activity significantly more than did statin dose-doubling (-28.0 versus -3.8 nmol/min per mL, P<0.05) and was comparable with R10 (-28.0 versus -18.6 nmol/min per mL; P>0.05); effects on Lp-PLA2 concentration were modest.. In diabetic patients with dyslipidemia, switching from statins to combination ES10/20 therapy generally improved lipoprotein subclass profile and Lp-PLA2 activity more than did statin dose-doubling and was comparable with R10, consistent with its lipid effects.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00862251.

Topics: 1-Alkyl-2-acetylglycerophosphocholine Esterase; Aged; Biomarkers; Cardiovascular Diseases; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Substitution; Dyslipidemias; Europe; Ezetimibe, Simvastatin Drug Combination; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lipoproteins; Male; Middle Aged; Risk Factors; South America; Time Factors; Treatment Outcome; United States

The objective was to assess the consistency of effect of switching to ezetimibe/simvastatin 10/20 mg versus doubling the baseline statin dose (to simvastatin 40 mg or atorvastatin 20 mg) or switching to rosuvastatin 10 mg across subgroups of subjects with (n = 617) and without (n = 191) metabolic syndrome (MetS).. This was a post hoc analysis of a randomized, double-blind, 6-week study of adults 18-79 years with cardiovascular disease and diabetes mellitus with low-density lipoprotein cholesterol (LDL-C) ≥70 and ≤160 mg/dl. The percent change in LDL-C and other lipids was estimated within each subgroup separately. Safety and tolerability were assessed.. In subjects with MetS, percent changes in LDL-C and other lipids were greater with ezetimibe/simvastatin versus doubling baseline statin or numerically greater versus switching to rosuvastatin, except high-density lipoprotein cholesterol and apolipoprotein (Apo) AI (mean percent changes in LDL-C were: -22.49% ezetimibe/simvastatin, -9.64% doubled baseline statin and -19.20% rosuvastatin). In subjects without MetS, percent changes in LDL-C, total cholesterol and Apo B were greater with ezetimibe/simvastatin versus doubling baseline statin or numerically greater versus switching to rosuvastatin (mean percent changes in LDL-C were: -25.14% ezetimibe/simvastatin, -4.75% doubled baseline statin and -19.75% rosuvastatin). Safety profiles were generally similar.. These results showed that switching to ezetimibe/simvastatin 10/20 mg was more effective at reducing LDL-C, total cholesterol and Apo B versus doubling the baseline statin dose to simvastatin 40 mg or atorvastatin 20 mg or switching to rosuvastatin 10 mg regardless of MetS status. These results were generally similar to those of the full cohort.

Topics: Adolescent; Adult; Aged; Anticholesteremic Agents; Apolipoproteins B; Atorvastatin; Azetidines; Blood Glucose; Cardiovascular Diseases; Cholesterol, LDL; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Drug Therapy, Combination; Ezetimibe, Simvastatin Drug Combination; Fasting; Female; Fluorobenzenes; Heptanoic Acids; Humans; Male; Metabolic Syndrome; Middle Aged; Pyrimidines; Pyrroles; Rosuvastatin Calcium; Simvastatin; Sulfonamides; Treatment Outcome