Effect of Switching From Statin Monotherapy to Ezetimibe/Simvastatin Combination Therapy Compared With Other Intensified Lipid-Lowering Strategies on Lipoprotein Subclasses in Diabetic Patients With Symptomatic Cardiovascular Disease.
BACKGROUND
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.


RESULTS
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.


CONCLUSIONS
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.


BACKGROUND
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00862251.
Biomarker Core Laboratory, Atlanta VAMC, Decatur, GA (N.A.L., P.F.W.).
Ngoc-Anh
NA
Le
Merck Research Laboratories, Kenilworth, NJ (J.E.T., A.M.T., D.R.N.).
Joanne E
JE
Tomassini
Merck Research Laboratories, Kenilworth, NJ (J.E.T., A.M.T., D.R.N.).
Andrew M
AM
Tershakovec
Merck Research Laboratories, Kenilworth, NJ (J.E.T., A.M.T., D.R.N.).
David R
DR
Neff
Biomarker Core Laboratory, Atlanta VAMC, Decatur, GA (N.A.L., P.F.W.) Emory University School of Medicine, Atlanta, GA (P.F.W.).
Peter W F
PW
Wilson
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000097:blood; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000209:etiology*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000175:diagnosis; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000175:diagnosis; D004311:Double-Blind Method; D057915:Drug Substitution; D050171:Dyslipidemias / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D005060:Europe; D000069499:Ezetimibe, Simvastatin Drug Combination / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D008074:Lipoproteins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D013020:South America; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States
D015415:Biomarkers; D000069499:Ezetimibe, Simvastatin Drug Combination; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008074:Lipoproteins; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C526684:PLA2G7 protein, human
NMR spectroscopy; diabetes mellitus; ezetimibe; lipoprotein particle number; lipoprotein subclasses; lipoprotein‐associated phospholipase A2; rosuvastatin; simvastatin