Ignite Creation Date:
2024-05-05 @ 5:31 PM
Last Modification Date:
2024-10-26 @ 9:32 AM
Study NCT ID:
NCT00474123
Status:
COMPLETED
Last Update Posted:
2010-07-14
First Post:
2007-05-15
Brief Title:
Antiplatelet and Anti-inflammatory Effects of Statins and Ezetimibe
Sponsor:
University of Sao Paulo
Organization:
University of Sao Paulo
Study Overview
Official Title:
Comparison of Antiplatelet and Anti-inflammatory Effects of High Dose Statin Monotherapy Versus Moderate Dose Statin Plus Ezetimibe
Status:
COMPLETED
Status Verified Date:
2010-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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 ezetimibesimvastatin
The investigators sought to compare the anti-inflammatory and anti-platelet effects of ezetimibe 10 mg simvastatin 20 mg E10S20 to simvastatin 80 mg S80
The investigators sought to compare the anti-inflammatory and anti-platelet effects of ezetimibe 10 mg simvastatin 20 mg E10S20 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 mgdL 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 E10S20 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
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 mgdL 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 E10S20 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None