Effects of Ezetimibe Add-On to Statin Therapy on Adipokine Production in Obese and Metabolic Syndrome Patients With Atherosclerosis
Condition: Metabolic Syndrome; Obesity; Coronary Artery Disease
MeSH terms: Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Atherosclerosis; Metabolic Syndrome; Syndrome
Study type: Interventional

Summary: 
      The purpose of this study is to investigate the effects of adding ezetimibe to statin therapy
      on levels of inflammatory markers and adipokines in patients with atherosclerosis disease and
      features of the metabolic syndrome,whose LDL-c remains above target (> 2.0 mmol/L) despite
      statin monotherapy.

      We hypothesize that the addition of Ezetimibe (10mg per day for 12 weeks) to ongoing statin
      therapy in patients with atherosclerosis and features of the metabolic syndrome will
      favourably modify levels of inflammatory biomarkers and adipokines.
    

Detailed description: 
      Atherosclerotic cardiovascular disease remains the leading cause of death in industrialized
      nations despite major advances in its diagnosis, treatment and prevention. While there has
      been a trend over the last half century showing a general decline in the age-adjusted death
      rates of heart disease and stroke, the increasing epidemic of obesity, followed closely by
      insulin resistance and type 2 diabetes will likely slow the decline and promise to reverse
      this trend.

      Obesity mediates increased cardiovascular disease risks through multiple pathways. Adipose
      tissue is no longer viewed as a passive repository for triacylglycerol storage and a source
      of free fatty acids (FFAs). It is recognized as a rich source of proinflammatory mediators,
      many of which are cytokines, growth factors and hormones that directly contribute to the
      proinflammatory milieu mediating vascular injury, insulin resistance and ultimately impacting
      on cardiovascular health. These proinflammatory adipocytokines, or adipokines include tumor
      necrosis factor- α (TNF α), interleukin-6 (IL-6), leptin, plasminogen activator inhibitor-1
      (PAI-1), angiotensinogen, resistin and more recently C-reactive protein (CRP). On the other
      hand, nitric oxide (NO) and another adipokine called adiponectin confer protection against
      inflammation and obesity-linked insulin resistance.

      The evolving role of augmented adipokine production in obese and insulin resistant states in
      cardiovascular disease risk opens new avenues for therapeutic interventions. Treatment of the
      metabolic syndrome will need to embrace new strategies to reduce the burden of
      proinflammatory adipokines. Lifestyle intervention remains the cornerstone therapy, but
      considerations should also be given to a number of drugs that can decrease the inflammatory
      adipokines.

      Ezetimibe selectively inhibits the absorption of biliary and dietary cholesterol and
      phytosterols at the intestinal brush border. When added to or coadministered with a statin,
      ezetimibe produces significant incremental LDL-C, apolipoprotein (apo) B, and triglyceride
      (TG) reductions, beneficial effects on high-density lipoprotein cholesterol (HDL-C) compared
      to statin monotherapy, and is well tolerated with a low incidence of side effects.

      It was previously demonstrated that in a 12 week trial that the addition of ezetimibe to
      simvastatin resulted in significant incremental reductions in CRP compared to simvastatin
      monotherapy.

      The outlined study protocol investigates the effects of adding ezetimibe to statin therapy on
      levels of inflammatory markers and adipokines in patients with atherosclerosis and features
      of the metabolic syndrome, whose LDL-c remains above target (> 2.0 mmol/L) despite statin
      monotherapy.
    

Intervention name(s): Ezetimibe
Intervention type(s): Drug
Intervention MeSH terms: Ezetimibe
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Ezetimibe; Statin; Low- density lipoprotein cholesterol; Adipokine; Adiponectin; C-reactive protein; Coronary artery disease; Metabolic Syndrome; Obesity