Calcium antagonist/statin combination improves artery elasticity

Small artery elasticity improves more with coadministration of amlodipine and atorvastatin compared with either treatment alone, said Jay N. Cohn, MD, at the 20th annual meeting of the American Society of Hypertension (ASH) in San Francisco. The additive effect of amlodipine and atorvastatin on small artery compliance may explain the superior clinical cardiovascular outcomes associated with the combination versus monotherapy with either drug.

Small artery compliance is reduced in the presence of endothelial dysfunction, and premature loss of arterial elasticity predicts the risk of developing cardiovascular disease, said Dr Cohn, a professor in the cardiovascular division of the department of medicine at the University of Minnesota Medical School. "We know that endothelial dysfunction is a very important contributor to morbid events occurring," he said.

Small artery compliance is an assessment of nitric oxide release and its bioactivity while the patient is at rest.

As part of ASCOT, 667 patients with hypertension and low-density lipoprotein (LDL) cholesterol levels of 100 to 250 mg/dL had measurements of vascular compliance performed at baseline, 8 weeks, and 28 weeks in response to 8 weeks of double-blind treatment with placebo, amlodipine 5 mg/d, atorvastatin 10 mg/d, or the 2 coadministered. The mean age of the patients was 56 years.

Small artery elasticity improved by 2.2% from baseline to 8 weeks with atorvastatin alone, by 11.6% with amlodipine alone, and by 19.6% with the combination. Patients who were assigned to the placebo group had a 2.1% decline in small artery compliance.

"When you put together a calcium antagonist and a statin, you get a dramatic improvement in endothelial function, which in fact may account for why these drugs have a favorable effect on outcomes," Dr Cohn said. "Since they are more than additive... the effect on endothelial function appears to be a direct consequence of these drugs and they're working through separate mechanisms."

Coadministration of amlodipine and atorvastatin produced sustained improvement in small artery elasticity through 28 weeks.