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Abstract: Objective:: This study assessed the effect of coadministration of ezetimibe and simvastatin on high sensitivity C-reactive protein (hs-CRP) in a large subject cohort (N =1089). Methods:: Data were combined from two nearly identical prospective trials. After dietary stabilization, washout period, and placebo lead-in period, patients with baseline low-density lipoprotein cholesterol (LDL-C)≥3.75–6.50mmol/l and triglycerides (TG)≤4.0mmol/l were randomized to one of the following daily treatments for 12 weeks: ezetimibe 10mg; simvastatin monotherapy (10, 20, 40, or 80mg); ezetimibe 10mg plus simvastatin (10, 20, 40, or 80mg); or placebo. The primary analysis was the percent change in hs-CRP for the pooled ezetimibe plus simvastatin versus simvastatin monotherapy cohorts. Results:: Ezetimibe coadministered with simvastatin more than doubled the hs-CRP reduction compared to simvastatin monotherapy (−33.3% versus −14.3%, p <0.01). At each individual simvastatin dose level, coadministration therapy exerted significant further incremental hs-CRP reductions compared to simvastatin monotherapy. Similar hs-CRP reductions with coadministered ezetimibe and simvastatin were observed in the major subgroups examined (coronary heart disease, gender, age, baseline LDL-C, and body mass index). Conclusion:: In this large subject cohort, ezetimibe coadministered with simvastatin significantly reduced hs-CRP, suggesting a possible additional anti-inflammatory/anti-atherosclerotic action of combination therapy compared to simvastatin monotherapy. [Copyright &y& Elsevier]