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

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 (5–10 mg/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) (3.8–2.3 mg/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 mmHg (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.