{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T03:02:17Z","timestamp":1788404537374,"version":"build-2803163510"},"reference-count":61,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2015,10,27]]},"abstract":"\n Background<\/jats:title>\n \n Patients with diabetes mellitus and cardiovascular disease may not achieve adequate low\u2010density lipoprotein cholesterol (\n LDL<\/jats:styled-content>\n \u2010C) lowering on statin monotherapy, attributed partly to atherogenic dyslipidemia. More intensive\n LDL<\/jats:styled-content>\n \u2010C\u2013lowering therapy can be considered for these patients. A previous randomized, controlled study demonstrated greater\n LDL<\/jats:styled-content>\n \u2010C lowering in diabetic patients with symptomatic cardiovascular disease who switched from simvastatin 20\u00a0mg (S20) or atorvastatin 10\u00a0mg (A10) to combination ezetimibe\/simvastatin 10\/20\u00a0mg (ES10\/20) therapy, compared with statin dose\u2010doubling (to S40 or A20) or switching to rosuvastatin 10\u00a0mg (R10). The effect of these regimens on novel biomarkers of atherogenic dyslipidemia (low\u2010 and high\u2010density lipoprotein particle number and lipoprotein\u2010associated phospholipase A2 [Lp\u2010PLA\n 2<\/jats:sub>\n ]) was assessed.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n Treatment effects on low\u2010 and high\u2010density lipoprotein particle number (\n by NMR<\/jats:styled-content>\n ) and Lp\u2010PLA\n 2<\/jats:sub>\n (by\n ELISA<\/jats:styled-content>\n ) were evaluated using plasma samples available from 358 subjects in the study. Switching to ES10\/20 reduced low\u2010density lipoprotein\u2010particle number numerically more than did statin dose\u2010doubling and was comparable with R10 (\u2212133.3, \u221294.4, and \u221256.3\u00a0nmol\/L, respectively;\n P<\/jats:italic>\n >0.05). Increases in high\u2010density lipoprotein particle number were significantly greater with switches to ES10\/20 versus statin dose\u2010doubling (1.5 and \u22120.5\u00a0\u03bcmol\/L;\n P<\/jats:italic>\n <0.05) and comparable with R10 (0.7\u00a0\u03bcmol\/L;\n P<\/jats:italic>\n >0.05). Percentages of patients attaining low\u2010density lipoprotein particle number levels <990\u00a0nmol\/L were 62.4% for ES10\/20, 54.1% for statin dose\u2010doubling, and 57.0% for R10. Switching to ES10\/20 reduced Lp\u2010PLA\n 2<\/jats:sub>\n activity significantly more than did statin dose\u2010doubling (\u221228.0 versus \u22123.8\u00a0nmol\/min per mL,\n P<\/jats:italic>\n <0.05) and was comparable with R10 (\u221228.0 versus \u221218.6\u00a0nmol\/min per mL;\n P<\/jats:italic>\n >0.05); effects on Lp\u2010PLA\n 2<\/jats:sub>\n concentration were modest.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n In diabetic patients with dyslipidemia, switching from statins to combination ES10\/20 therapy generally improved lipoprotein subclass profile and Lp\u2010PLA\n 2<\/jats:sub>\n activity more than did statin dose\u2010doubling and was comparable with R10, consistent with its lipid effects.\n <\/jats:p>\n <\/jats:sec>\n \n Clinical Trial Registration<\/jats:title>\n \n URL:\n http:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n . Unique identifier: NCT00862251.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.114.001675","type":"journal-article","created":{"date-parts":[[2015,10,21]],"date-time":"2015-10-21T01:57:45Z","timestamp":1445392665000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":23,"title":["Effect of Switching From Statin Monotherapy to Ezetimibe\/Simvastatin Combination Therapy Compared With Other Intensified Lipid\u2010Lowering Strategies on Lipoprotein Subclasses in Diabetic Patients With Symptomatic Cardiovascular Disease"],"prefix":"10.1161","volume":"4","author":[{"given":"Ngoc\u2010Anh","family":"Le","sequence":"first","affiliation":[{"name":"Biomarker Core Laboratory, Atlanta VAMC, Decatur, GA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne E.","family":"Tomassini","sequence":"additional","affiliation":[{"name":"Merck Research Laboratories, Kenilworth, NJ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew M.","family":"Tershakovec","sequence":"additional","affiliation":[{"name":"Merck Research Laboratories, Kenilworth, NJ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R.","family":"Neff","sequence":"additional","affiliation":[{"name":"Merck Research Laboratories, Kenilworth, NJ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter W. 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