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.


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.
Department of Cardiovascular Sciences and the Libin Cardiovascular Institute, University of Calgary, Calgary, AB, Canada.
François
F
Charbonneau
Todd J
TJ
Anderson
Lawrence
L
Title
Jean
J
Jobin
Paul
P
Poirier
Thao
T
Huyhn
Sammy
S
Chan
Ann
A
Walling
Stuart
S
Hutchison
Thang
T
Tran
Eva
E
Lonn
Jean
J
Buithieu
Jacques
J
Genest
D000328:Adult; D000368:Aged; D017311:Amlodipine / Q000008:administration & dosage* / Q000009:adverse effects; D001055:Apolipoproteins B / Q000097:blood; D000069059:Atorvastatin; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D001916:Brachial Artery / Q000000981:diagnostic imaging* / Q000502:physiology; D002121:Calcium Channel Blockers / Q000008:administration & dosage* / Q000009:adverse effects; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003324:Coronary Artery Disease / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000008:administration & dosage* / Q000009:adverse effects; D014280:Triglycerides / Q000097:blood; D014463:Ultrasonography; D014664:Vasodilation / Q000187:drug effects
D001055:Apolipoproteins B; D015415:Biomarkers; D002121:Calcium Channel Blockers; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D014280:Triglycerides; D017311:Amlodipine; D000069059:Atorvastatin