Modulation of arterial reactivity using amlodipine and atorvastatin measured by ultrasound examination (MARGAUX)

Atherosclerosis. 2008 Mar;197(1):420-7. doi: 10.1016/j.atherosclerosis.2007.06.019. Epub 2007 Aug 1.

Abstract

Objective: To evaluate the effect of the calcium channel blocker amlodipine on endothelial function in normotensive patients with coronary disease taking concomitant atorvastatin therapy.

Methods and results: Atorvastatin was titrated (10-80 mg/day) to maintain LDL-C<2.5 mmol/L and patients were randomized to receive amlodipine (5-10mg/day, n=64) or placebo (n=70) for 12 months. Brachial artery flow-mediated vasodilation (FMD) was assessed using vascular ultrasound. Inflammatory markers were also measured. At 12 months there was a significant decrease in mean low-density lipoprotein cholesterol (LDL-C) (4.4-2.1 mmol/L, P<0.0001), high-sensitivity C-reactive protein (hsCRP) (3.8-2.3mg/L, P<0.0001) and soluble vascular cell adhesion molecule-1 (sVCAM-1) (710-665 ng/mL, P<0.0001) for all patients, compared with baseline. Amlodipine was associated with a mean blood pressure reduction of 8/3 mm Hg (P<0.0001) whereas patients on placebo had no significant change. In the atorvastatin-placebo group, mean FMD increased (7.3-9.5%, P<0.05) with no change in nitroglycerin-mediated dilation. No further benefit on FMD or inflammatory markers was observed with the addition of amlodipine.

Conclusions: Intensive reduction of LDL-C with atorvastatin improves endothelium-dependent vasodilation and reduces markers of inflammation in patients with coronary disease. Amlodipine was not associated with a significant additional benefit on these variables.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Amlodipine / administration & dosage*
  • Amlodipine / adverse effects
  • Apolipoproteins B / blood
  • Atorvastatin
  • Biomarkers / blood
  • Blood Pressure / drug effects
  • Brachial Artery / diagnostic imaging*
  • Brachial Artery / physiology
  • Calcium Channel Blockers / administration & dosage*
  • Calcium Channel Blockers / adverse effects
  • Cholesterol, HDL / blood
  • Cholesterol, LDL / blood
  • Coronary Artery Disease / drug therapy*
  • Drug Therapy, Combination
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / physiology
  • Female
  • Heptanoic Acids / administration & dosage*
  • Heptanoic Acids / adverse effects
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects
  • Male
  • Middle Aged
  • Pyrroles / administration & dosage*
  • Pyrroles / adverse effects
  • Triglycerides / blood
  • Ultrasonography
  • Vasodilation / drug effects

Substances

  • Apolipoproteins B
  • Biomarkers
  • Calcium Channel Blockers
  • Cholesterol, HDL
  • Cholesterol, LDL
  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Pyrroles
  • Triglycerides
  • Amlodipine
  • Atorvastatin