Official Title: “Effects of Nicotinic Acid Plus Simvastatin Versus Simvastatin Alone on Carotid and Femoral Intima-Media Thickness in Patients With Peripheral Artery Disease (NASCIT)-A Randomized Controlled Trial”

Dyslipidaemia is characterized by low plasma levels of high-density lipoprotein cholesterol (HDL-c), elevated triglycerides and an increase in low density lipoprotein (LDL-c) particles, and has been unequivocally established as a most important cardiovascular risk factor. While statins are effective in reducing plasma levels of LDL-c, these drugs have only modest effects on raising HDL-c (typically by less than 10%), even with aggressive statin therapy.

However, increasing evidence suggests that low HDL-c might be at least as relevant as high LDL-c in promoting the development and progression of atherosclerosis. The beneficial effect of raising HDL-c on clinical outcome has already been demonstrated by several studies.

Nicotinic acid is the most potent agent available for raising plasma levels of HDL-c by up to 29% at clinically recommended doses, and substantially lowers triglycerides and LDL-c.

Furthermore, nicotinic acid is also the most potent lipid lowering agent available that reduces Lp(a), an independent marker of cardiovascular risk. In a recent study patients with coronary artery disease had a 21% increase in HDL-c and a 13% decrease in triglycerides, and these beneficial effects on lipid status may have contributed to a stabilization or regression of carotid intima-media-thickness (IMT).The impact in patients with advanced atherosclerosis like peripheral artery disease (PAD) in unknown.

We hypothesized that nicotinic acid in addition to statin therapy may inhibit progression of peripheral arterial atherosclerosis. Therefore, the aim of the present randomized controlled trial is to investigate the effects of nicotinic acid (daily dose starting with 500 mg, up to 2000mg) in addition to simvastatin (40 mg daily) vs. simvastatin (40mg daily) monotherapy in patients with low serum HDL-C levels and PAD with respect to changes of carotid and femoral IMT, changes of patients´ lipid status and occurrence of major adverse cardiovascular events (MACE).

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study

Intervention(s) in this Clinical Trial

• Drug: nicotinic acid in addition to simvastatin
  • Nicotinic acid in addition to simvastatin 40 mg

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 1
  • Nicotinic acid + Simvastatin
• Active Comparator: 2
  • Simvastatin

Primary Measures

• change of carotid and femoral IMT from baseline to 6 and 12 months follow up and occurrence of major adverse cardiovascular events (MACE)
  • Time Frame: 6 and 12 months
    Safety Issue?: No

Secondary Measures

• changes of grey scale median (GSM) score from baseline to follow-up, and changes of serum levels of total cholesterol, low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), triglycerides and lipoprotein (a).
  • Time Frame: 6 and 12 months
    Safety Issue?: No

Inclusion Criteria:

• PAD defined as an ABI ≤0.9 or >1.3 in patients with low serum HDL cholesterol levels (<45mg/dL in men, <55 mg/dL in women)

Exclusion Criteria:

• Elevated liver enzymes (above 2 times the normal level)
• Skeletal muscle myopathy or elevated serum CK levels
• Allergy or hypersensibility to either statins or nicotinic acid
• Women of childbearing potential

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Medical University of Vienna

Overall Clinical Trial Officials and Contacts

Renate Koppensteiner, Prof. Dr. Principal Investigator Division of Angiology, Department of Internal Medicine II, Medical University Vienna  

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00712049

Study ID Number: Version 1.0-2007

ClinicalTrials.gov Identifier: NCT00712049

Health Authority: Austria: Agency for Health and Food Safety