antiplatelet and anti-inflammatory effects of statins and ezetimibe

Conditions: Stable Angina

Summary: among patients with stable coronary artery disease (cad), it is not clear if the pleiotropic effects of cholesterol reduction differ between high-dose simvastatin alone and combined ezetimibe/simvastatin. the investigators sought to compare the anti-inflammatory and anti-platelet effects of ezetimibe 10 mg / simvastatin 20 mg (e10/s20) to simvastatin 80 mg (s80).

introduction among patients with coronary artery disease (cad), a robust evidence base supports the beneficial effects of statin therapy on mortality and other adverse cardiovascular outcomes . recently, two large trials , have demonstrated that compared to standard dose statin therapy, high statin doses reduced low-density lipoprotein-c (ldl-c) to extremely low levels and decreased coronary events, even in patients with normal levels of low-density lipoprotein-c (ldl-c). subsequently, recent guidelines have suggested an low-density lipoprotein-c (ldl-c) treatment goal of \<70 mg/dl in patients with coronary artery disease (cad). achieving such low low-density lipoprotein-c (ldl-c) levels frequently demands an intensive low-density lipoprotein-c (ldl-c) reduction, often above 50%. ezetimibe, an intestinal cholesterol absorption inhibitor, can be used as an additional therapy if statin monotherapy fails to reduce low-density lipoprotein-c (ldl-c) below the treatment goal. furthermore, anti-inflammatory and antithrombotic pleiotropic effects of statins might explain, at least in part, the large benefits demonstrated in randomized trials , . for example, in hypercholesterolemic patients treated with statins, a decrease in inflammation-associated markers such as the c-reactive protein (crp) has been described , although it is debated whether this effect is clearly independent of low-density lipoprotein-c (ldl-c). moreover, although inhibition of platelets by statin therapy is a well established effect , , it has not yet been clarified whether platelet inhibition by statin therapy depends on the reduction of low-density lipoprotein-c (ldl-c) or on the inhibition of intracellular signal pathways accompanied by disaggregating effects. two alternative pharmacologic strategies are equally effective in reducing low-density lipoprotein-c (ldl-c): high-dose statin alone and combined treatment with ezetimibe plus moderate-dose statin . it is not known whether these two strategies have different cholesterol-independent pleiotropic effects on inflammation and platelets. we therefore compared the anti-inflammatory and antiplatelet effects of two intensive pharmacologic strategies to reduce cholesterol: 80 mg of simvastatin (s80) versus 10 mg ezetimibe/ 20 mg of simvastatin (e10/s20). anti-inflammatory effects were assessed by performing serial measurements of the following biomarkers: c-reactive protein (crp), monocyte chemoattractant protein (mcp)-1, oxidized low-density lipoprotein-c (oxldl), soluble intercellular adhesion molecule (sicam)-1. platelet aggregation was also compared between the two strategies.

Eligibility criteria:
inclusion criteria: * stable angina * low-density lipoprotein (ldl) cholesterol 70-160 mg/dl exclusion criteria: * renal failure * age\>80 * simvastatin current treatment\>20mg * hepatic disease * inflammatory diseases

Keywords: angina atherosclerosis simvastatin ezetimibe inflammation