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Amlodipine and Atorvastatin Combination May Help Relax Arteries

By Ed Susman

SAN FRANCISCO, CA -- May 20, 2005 -- Two drugs that fight hypertension and hypercholesterolemia may also have the beneficial effect of making arteries less stiff, according to research reported here May 17^th at the 20^th Annual Scientific Meeting and Exposition of the American Society of Hypertension (ASH).

Using a device that measures arterial stiffness, Jay Cohn, MD, professor of medicine at the University of Minnesota School of Medicine in Minneapolis, Minnesota, United States, determined that the calcium channel blocker amlodipine (Norvasc) and the cholesterol-lowering agent atorvastatin (Lipitor) both reduce arterial stiffness in the small arteries.

"The small arteries—actually the microcirculation—play critical roles in heart disease and diabetes," said Dr. Cohn, who helped developed the HDI/Pulsewave CR-2000 device. Dr. Cohn acknowledged during his presentation that he has a vested interest in Hypertension Diagnostics, Inc., the company that manufactures the device that Dr. Cohn helped develop. It is used in research facilities throughout the United States and has applications for doctors' offices, Cohn said.

Using the device to perform pulse wave analysis, Dr. Cohn said that large artery elasticity was similarly improved by both amlodipine and its combination with atorvastatin, because both treatments resulted in similar reductions of blood pressure. But small artery elasticity, he emphasized, is dependent on nitric oxide generation by the inner lining of the small arteries. Amlodipine improved the small artery elasticity by 11.6%, significantly (P < .001) greater than with placebo, suggesting an increase in nitric oxide in the artery wall. The combination of amlodipine with atorvastatin, however, produced an even greater improvement of 19.6%, which was significantly greater than amlodipine alone (P < .03). Interestingly, the effect of atorvastatin alone was not significantly different from placebo.

Dr. Cohn said the large artery figures correspond to blood pressure lowering, or the impact that amlodipine had on the vessel wall.

In contrast, the small artery elasticity index was reduced 19.6 by the combination, 11.6 by amlodipine alone, 2.2 by atorvastatin alone, and -2.1 by placebo. The differences were statistically significant at the P < .001 for the combination versus placebo and P = .0011 for amlodipine versus placebo.

According to Dr. Cohn, the researchers were surprised at how quickly amlodipine fosters production of nitric oxide, which relaxes the endothelium and, therefore, the arteries. "Stiff arteries are old arteries," Dr. Cohn said. Relaxing the arteries is beneficial for cardiovascular health.

In the study, Dr. Cohn evaluated arterial stiffness in patients enrolled in the Atorvastatin and Amlodipine in Patients With Elevated Lipids and Hypertension (AVALON) study. That study demonstrated that amlodipine 5 mg administered once daily in combination with atorvastatin 10 mg is an effective treatment for concomitant hypertension/dyslipidemia, helping patients to achieve their guideline-mandated goals for both conditions.

"Coadministration of amlodipine and atorvastatin appeared to have a more than additive effect on vascular compliance, suggesting a potential synergy when compared with amlodipine alone," Dr. Cohn said. "The AVALON-AWC study strongly suggests that a greater early vascular benefit can be obtained from simultaneous treatment of hypertension and dyslipidemia. Coadministered therapy may contribute to additional vascular protection and reduction of cardiovascular events."

Daniel Lackland, DrPH, professor of epidemiology and medicine at the Medical University of South Carolina in Charleston, South Carolina, United States, said the pulsewave device could have significant utility in doctors' offices.

"Its use has been pretty well validated. It is a neat way to measure the arterial stiffness and could help doctors determine if a person with borderline high blood pressure figures is in need of medication or not," he said, suggesting that the device could be used to track how effective a medication is in a particular person.


[Presentation title: Early Improvements in Vascular Compliance Following Coadministration of Amlodipine and Atorvastatin in Patients With Concomitant Hypertension and Dyslipidemia: The AVALON Arterial Wall Compliance (AWC) Trial.]

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