Antiplatelet and Anti-inflammatory Effects of Statins and Ezetimibe
Condition: Stable Angina
MeSH terms: Angina, Stable
Study type: Interventional

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).
    

Detailed description: 
      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.
    

Intervention name(s): Simvastatin 80 mg/day for 6 weeks; Ezetimibe 10 mg / Simvastatin 20 mg
Intervention type(s): Drug; Drug
Intervention description(s): Simvastatin 80 mg/day, single dose, for 6 weeks.; Ezetimibe 10 mg / Simvastatin 20 mg
Patients were treated with daily Ezetimibe 10 mg / Simvastatin 20 mg for 6 weeks
Other intervention name(s): Simvastatin 80 mg (Zocor); Vytorin
Intervention MeSH terms: Simvastatin; Ezetimibe
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: angina; atherosclerosis; simvastatin; ezetimibe; inflammation