Abstract
BackgroundEzetimibe specifically blocks the absorption of dietary and biliary cholesterol and plant sterols. Synergism of ezetimibe-statin therapy on LDL-cholesterol has been demonstrated, but data concerning the pleiotropic effects of this combination are controversial.ObjectiveThis open-label trial evaluated whether the combination of simvastatin and ezetimibe also results in a synergistic effect that reduces the pro-inflammatory status of pre-diabetic subjects.MethodsFifty pre-diabetic subjects were randomly assigned to one of 2 groups, one receiving ezetimibe (10 mg/day), the other, simvastatin (20 mg/d) for 12 weeks, followed by an additional 12-week period of combined therapy. Blood samples were collected at baseline, 12 and 24 weeks. RESULTS: Total cholesterol, LDL-cholesterol and apolipoprotein B levels decreased in all the periods analyzed (p < 0.01), but triglycerides declined significantly only after combined therapy. Both drugs induced reductions in C-reactive protein, reaching statistical significance after combining ezetimibe with the simvastatin therapy (baseline 0.59 ± 0.14, simvastatin monotherapy 0.48 ± 0.12 mg/dL and 0.35 ± 0.12 mg/dL, p < 0.023). Such a reduction was independent of LDL-cholesterol change. However, mean levels of TNF-α and interleukin-6 and leukocyte count did not vary during the whole study.ConclusionExpected synergistic lowering effects of a simvastatin and ezetimibe combination on LDL-cholesterol, apolipoprotein B and triglycerides levels were confirmed in subjects with early disturbances of glucose metabolism. We suggest an additive effect of this combination also on inflammatory status based on the reduction of C-reactive protein. Attenuation of pro-inflammatory conditions may be relevant in reducing cardiometabolic risk.Title/ID of trial registrationEffect of simvastatin and ezetimibe on lipid and inflammation/NCT01103648.
Highlights
Long-term benefits of statins on primary and secondary prevention of cardiovascular events have been consistently shown in several populations [1,2,3]
Except for higher mean fasting plasma glucose for the group which started monotherapy with simvastatin, groups were similar regarding sociodemographic data, frequency of hypertension, mean values of blood pressure and biochemical variables. For those subjects who started the protocol with ezetimibe, did the mean values of body mass index (BMI) and abdominal circumference decrease significantly after monotherapy, but not following the combination therapy (Table 2)
No variation in these parameters was observed for the simvastatin group
Summary
Long-term benefits of statins on primary and secondary prevention of cardiovascular events have been consistently shown in several populations [1,2,3]. It has been demonstrated that, with particular regard to subjects at high risk, the lower LDL-cholesterol levels, the lower the incidence of cardiovascular outcomes [4,5]. The goal of 100 mg/dl for LDL-cholesterol may be too high for subjects at very high risk for whom a target of 70 mg/dL has been suggested [8,9] To achieve this goal, high statin doses may be necessary, which increases its adverse effects. Synergism of ezetimibe-statin therapy on LDL-cholesterol has been demonstrated, but data concerning the pleiotropic effects of this combination are controversial
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