Abstract 11388: A Randomized Trial Comparing the Pleotropic Effects of Ezetimibe Plus Moderate Dose Statin versus High Dose Statin Monotherapy
Background: In patients with stable coronary artery disease (CAD), it is not known if different strategies of LDL-lowering Results in different “pleotropic” antiplatelet and anti-inflammatory effects. We sought to test the effects of combined therapy with ezetimibe plus a moderate-dose simvastatin (E/S) vs. high dose simvastatin monotherapy (S) on platelet aggregation, inflammation and circulating endothelial progenitor cells (EPCs).
Methods: Stable CAD patients (n=83, 63±9 years, 48 men), previously on S20 mg, were randomly allocated to receive E10/S20 mg or S80 mg for 6 weeks. LDL-C, C-reactive protein (CRP), oxidized (ox) LDL, soluble (s) CD40 ligand (L), monocyte chemotactic protein (MCP)-1, interleukin (IL)-6, EPCs and platelet aggregation (platelet function analyzer [PFA]-100 closure time [CT]) were determined before and after treatment.
Results: Before treatment, E10/S20 and S80 patients presented, respectively, similar LDL-C (105±4.0 and 106±4.6 mg/dl), CRP (2.5±0.4 and 3.8±0.7 mg/l), oxLDL (79±5.9 and 78±5.1 ui/l), sCD40L (17±3.3 and 28±11.6 pg/ml), MCP-1 (221±13.3 and 232±12.0 pg/mL) and PFA-100 CT (156±11.1 and 157±12.5 sec). LDL-C and oxLDL were markedly reduced with both strategies but were not followed by changes of the other inflammation markers. PFA-100 CT increased significantly only among patients treated with E10/S20 mg. See Figure. Data are expressed as mean±SE. IL-6 and EPCs hardly changed with treatment in both groups.
Conclusions: These data suggest that, despite a comparable LDL-C reduction, the combination of ezetimibe + moderate dose simvastatin produces a similar anti-inflammatory effect and a greater platelet inhibition when compared to high dose simvastatin monotherapy. Doses 4x greater of simvastatin had no benefit on pleotropic anti-inflammatory effect. The potentially favorable antiplatelet effects of E10/S20 mg merit further study. Figure. Percentual changes of LDL-C, inflammation markers and PFA-100 CT.
- © 2010 by American Heart Association, Inc.